{ "$schema_version": "5.3", "review_mode": "fresh", "claim_restatement": { "index_wording": "Transcriptional Condensate Hypothesis", "entry_form": "phenomenon", "gradeable_restatement": "Endogenous transcriptional machinery forms liquid-liquid phase-separated condensates whose liquid state is required for transcription and is its primary organizing principle.", "restatement_required": true, "split_into": [], "parent_claim": null, "scope_qualifiers": [ { "qualifier": "Native versus engineered abundance, lineage, locus, activation/repression stage, tag and material-state definition set before outcomes", "determinable_before_outcome": true, "determined_from": "Enrollment and experimental design, before results; no responder-defined scope.", "action": "retained" } ] }, "hypothesis": { "name": "Transcriptional Condensate Hypothesis", "central_claim": "Endogenous transcriptional machinery forms liquid-liquid phase-separated condensates whose liquid state is required for transcription and is its primary organizing principle.", "proposed_mechanism": "Endogenous transcriptional machinery forms liquid-liquid phase-separated condensates whose liquid state is required for transcription and is its primary organizing principle.", "claimed_scope": "Endogenous transcriptional machinery forms liquid-liquid phase-separated condensates whose liquid state is required for transcription and is its primary organizing principle.", "claimed_level": [ "response", "maintenance" ], "is_conjunctive": true, "conjunctive_note": "Use the index LLPS-in-transcription conjunction. Puncta, recruitment, FRAP and sensitivity to hexanediol are not by themselves a phase-state diagnosis; assembly, biochemical interaction and LLPS-specific necessity remain separate subclaims." }, "rubric_routing": { "primary_rubric": "03-epigenetics-gene-regulation.md", "secondary_rubrics": [], "index_notes_applied": [ "Use the index LLPS-in-transcription conjunction. Puncta, recruitment, FRAP and sensitivity to hexanediol are not by themselves a phase-state diagnosis; assembly, biochemical interaction and LLPS-specific necessity remain separate subclaims." ], "rubric_fit_note": "Exact archived v5.3 framework. Any stale index empirical framing is rechecked against primary results." }, "subclaim_matrix": { "subclaims": [ { "id": "SC1", "statement": "Endogenous transcriptional machinery forms bona fide phase-separated condensates in vivo.", "subclaim_type": "existence", "scope": "endogenous concentration and locus/cell state set before outcomes", "claimed_scope": "endogenous concentration and locus/cell state set before outcomes", "governing_rubric": "03-epigenetics-gene-regulation.md", "key_evidence_anchor": "Quantitative phase-state measurements with concentration and binding controls", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Purified proteins and engineered systems phase separate, and native MYOCD, EWS and coactivators form measurable assemblies. Surface condensation, small DNA-bound networks and fitted nonequilibrium nucleation remain distinct alternatives to bona fide endogenous LLPS." }, { "id": "SC2", "statement": "The LLPS property is specifically required for transcriptional output.", "subclaim_type": "necessity", "scope": "native abundance and binding preserved under phase-selective perturbation", "claimed_scope": "native abundance and binding preserved under phase-selective perturbation", "governing_rubric": "03-epigenetics-gene-regulation.md", "key_evidence_anchor": "Phase-selective perturbation with interaction-matched rescue and nascent RNA", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "MYOCD and NELF preserve important occupancy/localization controls and use unrelated IDR rescue; these establish meaningful assembly contributions. CDT1 condensation without function and coupled cofactor affinity show that liquid state alone is not isolated. MYC phase switching demonstrates restricted engineered effects, not native global necessity." }, { "id": "SC3", "statement": "LLPS is the primary organizing principle of transcription at active loci.", "subclaim_type": "primacy", "scope": "representative prespecified active loci and lineages", "claimed_scope": "representative prespecified active loci and lineages", "governing_rubric": "03-epigenetics-gene-regulation.md", "key_evidence_anchor": "Disentanglement showing phase-state contribution dominates alternative biochemical mechanisms", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Native hubs without macroscopic LLPS, yeast CTD confinement, largely phase-insensitive MYC output and inhibitory droplets constrain universal primacy. Selected positive contexts do not dominate all competent biochemical recruitment models." } ], "aggregation_rule": "weakest-link", "aggregation_preregistered": true, "aggregation_rationale": "Use the index LLPS-in-transcription conjunction. Puncta, recruitment, FRAP and sensitivity to hexanediol are not by themselves a phase-state diagnosis; assembly, biochemical interaction and LLPS-specific necessity remain separate subclaims.", "primary_subclaim_id": "SC3", "aggregation_derivation": "Weakest-link aggregation yields Γ. SC1 has clear physical capacity and native assemblies but incomplete phase diagnosis; SC2 has strong selected assembly/rescue evidence without cleanly isolating liquid state from affinity and composition; SC3 lacks representative native phase-specific primacy. Stronger levels for multivalency models are not transferred to the stricter LLPS conjunction.", "aggregation_alternatives": { "weakest_link_would_return": "Γ", "primary_subclaim_would_return": "Γ", "scope_matched_would_return": "Γ", "note": "Separate narrow successes do not replace the preregistered gate." }, "index_rule_deviation": "" }, "competing_models": { "models_evaluated": [ { "rank_in_tournament": 1, "model_id": "M2", "is_nominal": false, "name": "Multivalent residence-time kinetic proofreading", "core_claim": "Weak cooperative interactions stabilize recruitment and reaction timing without requiring a bulk liquid phase.", "explains_what_nominal_does_not": "Weak cooperative interactions stabilize recruitment and reaction timing without requiring a bulk liquid phase.", "strongest_supporting_evidence": [ "Synthetic matched activators and native EWS target search support residence/recruitment mechanisms (35537448,29930090,38548891)." ], "strongest_contradictory_evidence": [ "MYOCD unrelated IDR rescue and measured native assemblies could contain material-state effects not captured by simple affinity (38489358)." ], "hsef_level_for_this_model": "Ε", "rationale": "Synthetic matched activators and native EWS target search support residence/recruitment mechanisms (35537448,29930090,38548891). MYOCD unrelated IDR rescue and measured native assemblies could contain material-state effects not captured by simple affinity (38489358)." }, { "rank_in_tournament": 2, "model_id": "M3", "is_nominal": false, "name": "DNA-mediated dynamic hubs", "core_claim": "DNA binding and cofactor networks nucleate finite dynamic assemblies.", "explains_what_nominal_does_not": "DNA binding and cofactor networks nucleate finite dynamic assemblies.", "strongest_supporting_evidence": [ "Native EWS hubs and CTD confinement support spatially restricted recruitment (29930090,42417395,38548891)." ], "strongest_contradictory_evidence": [ "RNA feedback and pH/IDR rescue show regulation beyond static DNA occupancy (33333019,40680734,33548202)." ], "hsef_level_for_this_model": "Ε", "rationale": "Native EWS hubs and CTD confinement support spatially restricted recruitment (29930090,42417395,38548891). RNA feedback and pH/IDR rescue show regulation beyond static DNA occupancy (33333019,40680734,33548202)." }, { "rank_in_tournament": 3, "model_id": "M4", "is_nominal": false, "name": "Phase separation coupled to percolation", "core_claim": "Composition-dependent networks can cooperate with, or oppose, phase separation and transcription.", "explains_what_nominal_does_not": "Composition-dependent networks can cooperate with, or oppose, phase separation and transcription.", "strongest_supporting_evidence": [ "Notch viscoelastic complexes and Gcn4 soluble/condensed comparisons support mixed assembly modes (39300145,40614721)." ], "strongest_contradictory_evidence": [ "Notch abundance and partner binding change, while Gcn4 cellular phase assignment is partly inferred; neither supplies generic endogenous phase necessity." ], "hsef_level_for_this_model": "Δ", "rationale": "Notch viscoelastic complexes and Gcn4 soluble/condensed comparisons support mixed assembly modes (39300145,40614721). Notch abundance and partner binding change, while Gcn4 cellular phase assignment is partly inferred; neither supplies generic endogenous phase necessity." }, { "rank_in_tournament": 4, "model_id": "M5", "is_nominal": false, "name": "Chromatin bridging-induced clustering", "core_claim": "Binding of multiple chromatin segments creates concentration and contact enrichment without bulk LLPS.", "explains_what_nominal_does_not": "Binding of multiple chromatin segments creates concentration and contact enrichment without bulk LLPS.", "strongest_supporting_evidence": [ "Surface-condensation and original polymer model offer plausible clustering physics (34569155,33885786)." ], "strongest_contradictory_evidence": [ "Original model is theoretical; selected native IDR rescue suggests composition-specific function beyond generic bridging (38489358)." ], "hsef_level_for_this_model": "Γ", "rationale": "Surface-condensation and original polymer model offer plausible clustering physics (34569155,33885786). Original model is theoretical; selected native IDR rescue suggests composition-specific function beyond generic bridging (38489358)." }, { "rank_in_tournament": 5, "model_id": "M1", "is_nominal": true, "name": "Classical liquid-liquid transcriptional condensates", "core_claim": "Distinct liquid phases broadly organize and are required for active transcription.", "explains_what_nominal_does_not": "Distinct liquid phases broadly organize and are required for active transcription.", "strongest_supporting_evidence": [ "Native MYOCD and NELF controlled IDR replacements plus BRD4 pH reversibility are the strongest supportive cases (38489358,33548202,40680734)." ], "strongest_contradictory_evidence": [ "Condensation without MYOCD function, limited MYC phase effects, soluble-complex alternatives and inhibitory droplets defeat broad phase-specific necessity (38489358,38811792,40614721,35537448)." ], "hsef_level_for_this_model": "Γ", "rationale": "Native MYOCD and NELF controlled IDR replacements plus BRD4 pH reversibility are the strongest supportive cases (38489358,33548202,40680734). Condensation without MYOCD function, limited MYC phase effects, soluble-complex alternatives and inhibitory droplets defeat broad phase-specific necessity (38489358,38811792,40614721,35537448)." } ], "tournament_summary": "Descriptive comparison; does not modify the nominal score. At a native locus, tune state reversibly while keeping DNA occupancy, cofactor affinity, concentration and activation-domain chemistry matched; compare matched biochemical-only rescue and measure nascent bursts alongside phase diagnostics.", "study_separating_rank1_from_rank2": "At a native locus, tune state reversibly while keeping DNA occupancy, cofactor affinity, concentration and activation-domain chemistry matched; compare matched biochemical-only rescue and measure nascent bursts alongside phase diagnostics.", "nominal_wins_only_by_funding_artifact": false, "level_unchanged_by_tournament": true }, "evidence_inventory": [ { "n": 1, "pmid": "33333019", "title": "RNA-Mediated Feedback Control of Transcriptional Condensates.", "citation": "Henninger JE, Oksuz O, Shrinivas K et al. RNA-Mediated Feedback Control of Transcriptional Condensates. Cell. 2021.", "doi": "10.1016/j.cell.2020.11.030", "pmcid": "PMC8128340", "url": "https://pubmed.ncbi.nlm.nih.gov/33333019/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33333019/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID33333019", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "reconstitution and cultured cells", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Low RNA promotes and high RNA dissolves electrostatic condensates with transcription feedback.", "what_it_does_not_show": "RNA changes binding and transcription chemistry; endogenous phase-selective necessity is not isolated.", "confounders_present": [ "RNA changes binding and transcription chemistry; endogenous phase-selective necessity is not isolated." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 2, "pmid": "32386547", "title": "Unblending of Transcriptional Condensates in Human Repeat Expansion Disease.", "citation": "Basu S, Mackowiak SD, Niskanen H et al. Unblending of Transcriptional Condensates in Human Repeat Expansion Disease. Cell. 2020.", "doi": "10.1016/j.cell.2020.04.018", "pmcid": "PMC7261253", "url": "https://pubmed.ncbi.nlm.nih.gov/32386547/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32386547/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID32386547", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "human disease variants and mouse model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "HOXD13 repeat expansion changes co-condensation and cell-specific developmental transcription.", "what_it_does_not_show": "Repeat changes also alter interactions/aggregation; human variant effects do not uniquely attribute liquid state.", "confounders_present": [ "Repeat changes also alter interactions/aggregation; human variant effects do not uniquely attribute liquid state." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 3, "pmid": "29930094", "title": "Mediator and RNA polymerase II clusters associate in transcription-dependent condensates.", "citation": "Cho WK, Spille JH, Hecht M et al. Mediator and RNA polymerase II clusters associate in transcription-dependent condensates. Science (New York, N.Y.). 2018.", "doi": "10.1126/science.aar4199", "pmcid": "PMC6543815", "url": "https://pubmed.ncbi.nlm.nih.gov/29930094/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29930094/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID29930094", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "live mouse embryonic stem cells", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Mediator and Pol II form dynamic clusters that colocalize and respond to transcription inhibitors.", "what_it_does_not_show": "Puncta, dynamics and inhibitor sensitivity do not establish phase boundary or phase-state necessity.", "confounders_present": [ "Puncta, dynamics and inhibitor sensitivity do not establish phase boundary or phase-state necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 4, "pmid": "34375583", "title": "Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation.", "citation": "Lee JH, Wang R, Xiong F et al. Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation. Molecular cell. 2021.", "doi": "10.1016/j.molcel.2021.07.024", "pmcid": "PMC8383322", "url": "https://pubmed.ncbi.nlm.nih.gov/34375583/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34375583/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID34375583", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "nascent RNA mapping and cultured cells", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "m6A-eRNAs recruit YTHDC1/BRD4 and depletion reduces enhancer activation.", "what_it_does_not_show": "Reader depletion and IDR/arginine changes also affect RNA/cofactor binding; state specificity remains.", "confounders_present": [ "Reader depletion and IDR/arginine changes also affect RNA/cofactor binding; state specificity remains." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 5, "pmid": "40680734", "title": "Regulation of inflammatory responses by pH-dependent transcriptional condensates.", "citation": "Wu Z, Pope SD, Ahmed NS et al. Regulation of inflammatory responses by pH-dependent transcriptional condensates. Cell. 2025.", "doi": "10.1016/j.cell.2025.06.033", "pmcid": "PMC12313145", "url": "https://pubmed.ncbi.nlm.nih.gov/40680734/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40680734/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID40680734", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph7, 1:Results:paragraph12, 1:Results:paragraph13, 1:Results:paragraph14, 1:Results:paragraph15. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "macrophages and in vivo inflammation", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Acidic pH disrupts BRD4/MED1 assemblies and changes inflammatory output through histidine-rich regions.", "what_it_does_not_show": "Stable protein abundance, isolated nuclei, reversible pH and functional segment mutants narrow generic collapse; protonation affects molecular affinities and phase together. FRAP/alcohol are not specific state diagnoses.", "confounders_present": [ "Stable protein abundance, isolated nuclei, reversible pH and functional segment mutants narrow generic collapse; protonation affects molecular affinities and phase together. FRAP/alcohol are not specific state diagnoses." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 6, "pmid": "38194964", "title": "Direct observation of a condensate effect on super-enhancer controlled gene bursting.", "citation": "Du M, Stitzinger SH, Spille JH et al. Direct observation of a condensate effect on super-enhancer controlled gene bursting. Cell. 2024.", "doi": "10.1016/j.cell.2023.12.005", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38194964/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38194964/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID38614098" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID38194964", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "endogenous Sox2 live imaging", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Nearby condensate enhances burst size/frequency while basal output persists when distant; local DNA/cohesin perturbations affect enhancement.", "what_it_does_not_show": "Assembly position is not itself liquid diagnosis; DNA/protein perturbations affect other functions. Erratum linked, body audit pending.", "confounders_present": [ "Assembly position is not itself liquid diagnosis; DNA/protein perturbations affect other functions. Erratum linked, body audit pending." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 7, "pmid": "38811792", "title": "MYC phase separation selectively modulates the transcriptome.", "citation": "Yang J, Chung CI, Koach J et al. MYC phase separation selectively modulates the transcriptome. Nature structural & molecular biology. 2024.", "doi": "10.1038/s41594-024-01322-6", "pmcid": "PMC11479839", "url": "https://pubmed.ncbi.nlm.nih.gov/38811792/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38811792/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID38867115" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID38811792", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:RESULTS:paragraph14, 1:RESULTS:paragraph18, 1:RESULTS:paragraph20, 1:RESULTS:paragraph21, 1:RESULTS:paragraph22, 1:RESULTS:paragraph23. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "chemogenetically controlled MYCN cultured cells", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Matched N-myc levels show phase separation further modulates fewer than three percent of regulated genes with proliferation effects.", "what_it_does_not_show": "Engineered state/overexpression and small affected set constrain broad primacy; correction linked, body audit pending.", "confounders_present": [ "Engineered state/overexpression and small affected set constrain broad primacy; correction linked, body audit pending." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 8, "pmid": "35537448", "title": "Transcription activation is enhanced by multivalent interactions independent of phase separation.", "citation": "Trojanowski J, Frank L, Rademacher A et al. Transcription activation is enhanced by multivalent interactions independent of phase separation. Molecular cell. 2022.", "doi": "10.1016/j.molcel.2022.04.017", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/35537448/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35537448/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID35537448", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: Scite body characters 0-8000, Scite body characters 16000-24000, Scite body characters 32000-40000. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "synthetic TF reporter array", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Multivalent interactions enhance occupancy/residence/cofactor recruitment; droplets are neutral or inhibitory for output.", "what_it_does_not_show": "Reporter and synthetic platform cannot refute all endogenous contexts; it separates assembly benefits from droplet state.", "confounders_present": [ "Reporter and synthetic platform cannot refute all endogenous contexts; it separates assembly benefits from droplet state." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 9, "pmid": "32929202", "title": "Nucleated transcriptional condensates amplify gene expression.", "citation": "Wei MT, Chang YC, Shimobayashi SF et al. Nucleated transcriptional condensates amplify gene expression. Nature cell biology. 2020.", "doi": "10.1038/s41556-020-00578-6", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32929202/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32929202/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID32929202", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "optogenetic FET/TAF15 system", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "CTD clusters nucleate engineered TAF15 condensates and amplify transcription.", "what_it_does_not_show": "Optogenetic concentration and FET interactions establish capacity, not endogenous universal need.", "confounders_present": [ "Optogenetic concentration and FET interactions establish capacity, not endogenous universal need." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 10, "pmid": "35864192", "title": "Hijacking of transcriptional condensates by endogenous retroviruses.", "citation": "Asimi V, Sampath Kumar A, Niskanen H et al. Hijacking of transcriptional condensates by endogenous retroviruses. Nature genetics. 2022.", "doi": "10.1038/s41588-022-01132-w", "pmcid": "PMC9355880", "url": "https://pubmed.ncbi.nlm.nih.gov/35864192/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35864192/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID35864192", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse stem cells and embryos", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "TRIM28 degradation shifts assemblies to ERVs; RNA knockdown or TF overexpression rescues localization.", "what_it_does_not_show": "TRIM28/RNA/TF changes alter gene regulation directly; condensate relocalization is not selective liquid-state intervention.", "confounders_present": [ "TRIM28/RNA/TF changes alter gene regulation directly; condensate relocalization is not selective liquid-state intervention." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 11, "pmid": "31398323", "title": "Enhancer Features that Drive Formation of Transcriptional Condensates.", "citation": "Shrinivas K, Sabari BR, Coffey EL et al. Enhancer Features that Drive Formation of Transcriptional Condensates. Molecular cell. 2019.", "doi": "10.1016/j.molcel.2019.07.009", "pmcid": "PMC6690378", "url": "https://pubmed.ncbi.nlm.nih.gov/31398323/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31398323/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID31398323", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "DNA/coactivator reconstitution and cellular enhancers", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "TF site density/affinity thresholds support cooperative condensation and enhancer output.", "what_it_does_not_show": "DNA binding and recruitment share thresholds; phase-specific endogenous output not isolated.", "confounders_present": [ "DNA binding and recruitment share thresholds; phase-specific endogenous output not isolated." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 12, "pmid": "33053359", "title": "Phase-Separated Transcriptional Condensates Accelerate Target-Search Process Revealed by Live-Cell Single-Molecule Imaging.", "citation": "Kent S, Brown K, Yang CH et al. Phase-Separated Transcriptional Condensates Accelerate Target-Search Process Revealed by Live-Cell Single-Molecule Imaging. Cell reports. 2020.", "doi": "10.1016/j.celrep.2020.108248", "pmcid": "PMC7593837", "url": "https://pubmed.ncbi.nlm.nih.gov/33053359/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33053359/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID33053359", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "live Polycomb-regulated cells", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "CBX2-DNA interactions nucleate assemblies and accelerate repeated target search.", "what_it_does_not_show": "DNA binding and rebinding can produce hubs; repression differs from broad active-locus primacy.", "confounders_present": [ "DNA binding and rebinding can produce hubs; repression differs from broad active-locus primacy." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 13, "pmid": "39169234", "title": "Mechanism for controlled assembly of transcriptional condensates by Aire.", "citation": "Huoh YS, Zhang Q, Törner R et al. Mechanism for controlled assembly of transcriptional condensates by Aire. Nature immunology. 2024.", "doi": "10.1038/s41590-024-01922-w", "pmcid": "PMC11362013", "url": "https://pubmed.ncbi.nlm.nih.gov/39169234/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39169234/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID39169234", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "Aire regulatory cells", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Aire polymerization, histone binding and coactivator recruitment balance enhancer assemblies and transcription.", "what_it_does_not_show": "Controlled polymerization is a network assembly mechanism; liquid demixing and functional specificity are separate.", "confounders_present": [ "Controlled polymerization is a network assembly mechanism; liquid demixing and functional specificity are separate." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 14, "pmid": "38489358", "title": "Coactivator condensation drives cardiovascular cell lineage specification.", "citation": "Gan P, Eppert M, De La Cruz N et al. Coactivator condensation drives cardiovascular cell lineage specification. Science advances. 2024.", "doi": "10.1126/sciadv.adk7160", "pmcid": "PMC10942106", "url": "https://pubmed.ncbi.nlm.nih.gov/38489358/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38489358/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID38489358", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:RESULTS:paragraph4, 1:RESULTS:paragraph6, 1:RESULTS:paragraph14, 1:RESULTS:paragraph18, 1:RESULTS:paragraph19, 1:RESULTS:paragraph22, 1:RESULTS:paragraph25. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "cardiovascular differentiation and reprogramming", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Endogenous MYOCD knock-in differentiation shows hubs at measured native concentrations; matched-expression aromatic IDR replacements rescue reprogramming and preserve DNA occupancy.", "what_it_does_not_show": "CDT1 replacement restores condensates and high DNA occupancy but not p300 recruitment, acetylation or output; chemistry and composition matter, while liquid state alone remains unisolated.", "confounders_present": [ "CDT1 replacement restores condensates and high DNA occupancy but not p300 recruitment, acetylation or output; chemistry and composition matter, while liquid state alone remains unisolated." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 15, "pmid": "33548202", "title": "Stress-induced nuclear condensation of NELF drives transcriptional downregulation.", "citation": "Rawat P, Boehning M, Hummel B et al. Stress-induced nuclear condensation of NELF drives transcriptional downregulation. Molecular cell. 2021.", "doi": "10.1016/j.molcel.2021.01.016", "pmcid": "PMC7939545", "url": "https://pubmed.ncbi.nlm.nih.gov/33548202/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33548202/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID33548202", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph58, 1:Results:paragraph71. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "stressed human cells", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "NELF IDR replacement with FUS/EWS supports stress-dependent promoter recruitment and downregulation.", "what_it_does_not_show": "Nuclear localization, complex incorporation and basal promoter binding are preserved after IDR deletion; stress-dependent occupancy changes. FUS/EWS replacements constitutively repress and improve survival, but chemical recruitment and material state remain coupled.", "confounders_present": [ "Nuclear localization, complex incorporation and basal promoter binding are preserved after IDR deletion; stress-dependent occupancy changes. FUS/EWS replacements constitutively repress and improve survival, but chemical recruitment and material state remain coupled." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 16, "pmid": "31543265", "title": "Organization of Chromatin by Intrinsic and Regulated Phase Separation.", "citation": "Gibson BA, Doolittle LK, Schneider MWG et al. Organization of Chromatin by Intrinsic and Regulated Phase Separation. Cell. 2019.", "doi": "10.1016/j.cell.2019.08.037", "pmcid": "PMC6778041", "url": "https://pubmed.ncbi.nlm.nih.gov/31543265/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31543265/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID31543265", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Weak", "system": "reconstituted and microinjected chromatin", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Histone tails, H1/linker length and acetylation tune chromatin droplets; acetylated chromatin co-condenses with BRD4.", "what_it_does_not_show": "Microinjected/reconstituted polymer capacity is not endogenous active transcription liquid-state necessity.", "confounders_present": [ "Microinjected/reconstituted polymer capacity is not endogenous active transcription liquid-state necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [ "Reconstituted chromatin physical capacity; not another endogenous transcription phase-necessity test." ] }, { "n": 17, "pmid": "38049566", "title": "Rational optimization of a transcription factor activation domain inhibitor.", "citation": "Basu S, Martínez-Cristóbal P, Frigolé-Vivas M et al. Rational optimization of a transcription factor activation domain inhibitor. Nature structural & molecular biology. 2023.", "doi": "10.1038/s41594-023-01159-5", "pmcid": "PMC10716049", "url": "https://pubmed.ncbi.nlm.nih.gov/38049566/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38049566/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID38049566", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "androgen-receptor cancer cells and in vivo models", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "AD-directed optimized compounds reduce AR transcription and tumour effects with target affinity.", "what_it_does_not_show": "AD interaction/nuclear entry effects accompany condensation; drug efficacy is not a phase-only perturbation.", "confounders_present": [ "AD interaction/nuclear entry effects accompany condensation; drug efficacy is not a phase-only perturbation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 18, "pmid": "31563432", "title": "Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes.", "citation": "Zamudio AV, Dall'Agnese A, Henninger JE et al. Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes. Molecular cell. 2019.", "doi": "10.1016/j.molcel.2019.08.016", "pmcid": "PMC6898777", "url": "https://pubmed.ncbi.nlm.nih.gov/31563432/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31563432/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID31563432", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "signalling and coactivator systems", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Signalling-factor IDRs partition with Mediator and beta-catenin occupies selected enhancers through multiple interactions.", "what_it_does_not_show": "DNA-binding and cofactor interactions can localize signals without unique phase necessity.", "confounders_present": [ "DNA-binding and cofactor interactions can localize signals without unique phase necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 19, "pmid": "36327976", "title": "Inducible transcriptional condensates drive 3D genome reorganization in the heat shock response.", "citation": "Chowdhary S, Kainth AS, Paracha S et al. Inducible transcriptional condensates drive 3D genome reorganization in the heat shock response. Molecular cell. 2022.", "doi": "10.1016/j.molcel.2022.10.013", "pmcid": "PMC9701134", "url": "https://pubmed.ncbi.nlm.nih.gov/36327976/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36327976/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID36327976", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "yeast heat-shock response", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Hsf1/Hsp70/IDR mutations alter clusters, intergenic coalescence and fitness.", "what_it_does_not_show": "Stress and protein binding changes remain coupled; networked clustering need not diagnose classical isotropic LLPS.", "confounders_present": [ "Stress and protein binding changes remain coupled; networked clustering need not diagnose classical isotropic LLPS." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 20, "pmid": "33885786", "title": "Slow chromatin dynamics enhances promoter accessibility to transcriptional condensates.", "citation": "Yamamoto T, Sakaue T, Schiessel H. Slow chromatin dynamics enhances promoter accessibility to transcriptional condensates. Nucleic acids research. 2021.", "doi": "10.1093/nar/gkab275", "pmcid": "PMC8136786", "url": "https://pubmed.ncbi.nlm.nih.gov/33885786/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33885786/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID33885786", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "original polymer-dynamics theory", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Model predicts extrusion-dependent promoter contact probabilities from linker relaxation.", "what_it_does_not_show": "Original theoretical research, not empirical phase-state or transcription necessity; assumptions require tests.", "confounders_present": [ "Original theoretical research, not empirical phase-state or transcription necessity; assumptions require tests." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 21, "pmid": "29930091", "title": "Coactivator condensation at super-enhancers links phase separation and gene control.", "citation": "Sabari BR, Dall'Agnese A, Boija A et al. Coactivator condensation at super-enhancers links phase separation and gene control. Science (New York, N.Y.). 2018.", "doi": "10.1126/science.aar3958", "pmcid": "PMC6092193", "url": "https://pubmed.ncbi.nlm.nih.gov/29930091/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29930091/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID29930091", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 3:Coactivator puncta and super-enhancer occupancy are sensitive to condensate perturbation, 5:MED1-IDR participates in liquid-liquid phase separation in cells, 6:Conserved serine bias in the MED1-IDR is necessary for phase separation, 7:MED1-IDR droplets can incorporate proteins necessary for transcription. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "stem cells and purified coactivator IDRs", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "BRD4/MED1 puncta at super-enhancers, chemical sensitivity and IDR droplets support condensation capacity.", "what_it_does_not_show": "Puncta, FRAP, hexanediol and extract compartmentalization cannot isolate endogenous liquid-state necessity.", "confounders_present": [ "Puncta, FRAP, hexanediol and extract compartmentalization cannot isolate endogenous liquid-state necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 22, "pmid": "30449618", "title": "Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains.", "citation": "Boija A, Klein IA, Sabari BR et al. Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains. Cell. 2018.", "doi": "10.1016/j.cell.2018.10.042", "pmcid": "PMC6295254", "url": "https://pubmed.ncbi.nlm.nih.gov/30449618/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30449618/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID30449618", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "TF/Mediator reconstitution and cells", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "AD residues jointly control droplet propensity and transcriptional activity.", "what_it_does_not_show": "Same residues mediate cofactor affinity; correlated losses do not separate phase from binding.", "confounders_present": [ "Same residues mediate cofactor affinity; correlated losses do not separate phase from binding." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 23, "pmid": "40377985", "title": "Phase separation of the oncogenic fusion protein EWS::FLI1 is modulated by its DNA-binding domain.", "citation": "Selig EE, Sohn EJ, Stoja A et al. Phase separation of the oncogenic fusion protein EWS::FLI1 is modulated by its DNA-binding domain. Proceedings of the National Academy of Sciences of the United States of America. 2025.", "doi": "10.1073/pnas.2221823122", "pmcid": "PMC12107149", "url": "https://pubmed.ncbi.nlm.nih.gov/40377985/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40377985/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID40377985", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "purified EWS-FLI1 and related domains", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "FLI1/ETS DNA-binding domains enhance EWS assembly, whereas DNA binding suppresses these interactions and condensation.", "what_it_does_not_show": "Biophysical reconstitution, not native transcription necessity; shows DBD and LCD functions are intertwined.", "confounders_present": [ "Biophysical reconstitution, not native transcription necessity; shows DBD and LCD functions are intertwined." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 24, "pmid": "34916619", "title": "Phase separation of RNA-binding protein promotes polymerase binding and transcription.", "citation": "Shao W, Bi X, Pan Y et al. Phase separation of RNA-binding protein promotes polymerase binding and transcription. Nature chemical biology. 2022.", "doi": "10.1038/s41589-021-00904-5", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34916619/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34916619/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID34916619", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse embryonic stem cells", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "PSPC1 links RNA/Pol II engagement; acute degradation impairs polymerase binding and nascent transcription.", "what_it_does_not_show": "PSPC1 RNA binding and polymerase chemistry change with loss; binding-matched phase rescue must be demonstrated.", "confounders_present": [ "PSPC1 RNA binding and polymerase chemistry change with loss; binding-matched phase rescue must be demonstrated." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 25, "pmid": "37291424", "title": "RNA polymerase II depletion from the inactive X chromosome territory is not mediated by physical compartmentalization.", "citation": "Collombet S, Rall I, Dugast-Darzacq C et al. RNA polymerase II depletion from the inactive X chromosome territory is not mediated by physical compartmentalization. Nature structural & molecular biology. 2023.", "doi": "10.1038/s41594-023-01008-5", "pmcid": "PMC10442225", "url": "https://pubmed.ncbi.nlm.nih.gov/37291424/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37291424/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID37291424", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "X-inactivation single-particle tracking", "decisive_perturbation": true, "endogenous": true, "direction": "contradicts", "what_it_shows": "Pol II enters Xist territory; apparent depletion reflects loss of chromatin-bound fraction.", "what_it_does_not_show": "Inactive-X initiation context differs from active loci; disproves a proposed diffusion barrier, not every phase assembly.", "confounders_present": [ "Inactive-X initiation context differs from active loci; disproves a proposed diffusion barrier, not every phase assembly." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 26, "pmid": "34903620", "title": "Phase Separation Mediates NUP98 Fusion Oncoprotein Leukemic Transformation.", "citation": "Chandra B, Michmerhuizen NL, Shirnekhi HK et al. Phase Separation Mediates NUP98 Fusion Oncoprotein Leukemic Transformation. Cancer discovery. 2022.", "doi": "10.1158/2159-8290.CD-21-0674", "pmcid": "PMC8983581", "url": "https://pubmed.ncbi.nlm.nih.gov/34903620/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34903620/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID34903620", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "NUP98-fusion hematopoietic transformation", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Homotypic/heterotypic interaction changes affect puncta, aberrant transcription and transformation.", "what_it_does_not_show": "Oncofusion and ectopic construct scope; interacting residues and chromatin binding must remain matched for LLPS attribution.", "confounders_present": [ "Oncofusion and ectopic construct scope; interacting residues and chromatin binding must remain matched for LLPS attribution." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 27, "pmid": "36603581", "title": "Functional partitioning of transcriptional regulators by patterned charge blocks.", "citation": "Lyons H, Veettil RT, Pradhan P et al. Functional partitioning of transcriptional regulators by patterned charge blocks. Cell. 2023.", "doi": "10.1016/j.cell.2022.12.013", "pmcid": "PMC9910284", "url": "https://pubmed.ncbi.nlm.nih.gov/36603581/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36603581/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID36603581", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "MED1 reconstitution and cellular transitions", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Patterned charge blocks determine functional partitioning and gene activation during transition.", "what_it_does_not_show": "Charge sequence tunes affinity and RNA/protein binding as well as phase; selective liquid property not fully disentangled.", "confounders_present": [ "Charge sequence tunes affinity and RNA/protein binding as well as phase; selective liquid property not fully disentangled." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 28, "pmid": "31792379", "title": "Phase separation of YAP reorganizes genome topology for long-term YAP target gene expression.", "citation": "Cai D, Feliciano D, Dong P et al. Phase separation of YAP reorganizes genome topology for long-term YAP target gene expression. Nature cell biology. 2019.", "doi": "10.1038/s41556-019-0433-z", "pmcid": "PMC8259329", "url": "https://pubmed.ncbi.nlm.nih.gov/31792379/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31792379/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID31792379", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "hyperosmotic YAP response", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "YAP assemblies recruit TEAD/TAZ and eventually Pol II; AD deletion suppresses assembly and signalling.", "what_it_does_not_show": "Osmotic crowding and activation-domain chemistry accompany assembly; physiological unstressed scope differs.", "confounders_present": [ "Osmotic crowding and activation-domain chemistry accompany assembly; physiological unstressed scope differs." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 29, "pmid": "39300145", "title": "Notch1 Phase Separation Coupled Percolation facilitates target gene expression and enhancer looping.", "citation": "Foran G, Hallam RD, Megaly M et al. Notch1 Phase Separation Coupled Percolation facilitates target gene expression and enhancer looping. Scientific reports. 2024.", "doi": "10.1038/s41598-024-71634-6", "pmcid": "PMC11413390", "url": "https://pubmed.ncbi.nlm.nih.gov/39300145/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39300145/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID39131356" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID39300145", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph3, 1:Results:paragraph19, 1:Results:paragraph20, 1:Results:paragraph23, 1:Results:paragraph25. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "human Notch signalling cells", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "NICD forms transcription assemblies and enhancer loops, with phase separation coupled to percolation model.", "what_it_does_not_show": "TAD changes affect activation surfaces; viscoelastic network and classical liquid demixing are distinct propositions. Final replaces preprint39131356.", "confounders_present": [ "TAD changes affect activation surfaces; viscoelastic network and classical liquid demixing are distinct propositions. Final replaces preprint39131356." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [ "Updates39131356 preprint, excluded." ] }, { "n": 30, "pmid": "29930090", "title": "Imaging dynamic and selective low-complexity domain interactions that control gene transcription.", "citation": "Chong S, Dugast-Darzacq C, Liu Z et al. Imaging dynamic and selective low-complexity domain interactions that control gene transcription. Science (New York, N.Y.). 2018.", "doi": "10.1126/science.aar2555", "pmcid": "PMC6961784", "url": "https://pubmed.ncbi.nlm.nih.gov/29930090/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29930090/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "EWS-native-hub-programme", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 4:EWS/FLI1 forms hubs at endogenous GGAA microsatellites, 5:Dynamic EWS LCD-LCD interactions mediate formation of EWS/FLI1 hubs, 6:EWS LCD-LCD interactions are essential for transcription and transformation\nfunctions of EWS/FLI1. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "synthetic arrays and endogenous Ewing-sarcoma loci", "decisive_perturbation": true, "endogenous": true, "direction": "contradicts", "what_it_shows": "Dynamic LCD hubs stabilize DNA binding and activate transcription without detectable phase separation at physiological abundance.", "what_it_does_not_show": "Native hub interactions are real; lack of detected bulk LLPS cannot exclude subresolution or coupled transitions.", "confounders_present": [ "Native hub interactions are real; lack of detected bulk LLPS cannot exclude subresolution or coupled transitions." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 31, "pmid": "32707132", "title": "The CTD Is Not Essential for the Post-Initiation Control of RNA Polymerase II Activity.", "citation": "Gerber A, Roeder RG. The CTD Is Not Essential for the Post-Initiation Control of RNA Polymerase II Activity. Journal of molecular biology. 2020.", "doi": "10.1016/j.jmb.2020.07.010", "pmcid": "PMC7502503", "url": "https://pubmed.ncbi.nlm.nih.gov/32707132/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32707132/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID32707132", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "inducible endogenous Pol II system", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Post-initiation CTD ablation preserves pause maintenance and productive release.", "what_it_does_not_show": "Stage-specific test does not refute CTD initiation function or all phase pathways.", "confounders_present": [ "Stage-specific test does not refute CTD initiation function or all phase pathways." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 32, "pmid": "40914169", "title": "Endogenous YAP/TAZ partitioning in TEAD condensates orchestrates the Hippo response.", "citation": "Zhu T, Li H, Mao S et al. Endogenous YAP/TAZ partitioning in TEAD condensates orchestrates the Hippo response. Molecular cell. 2025.", "doi": "10.1016/j.molcel.2025.08.014", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40914169/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40914169/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID40914169", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "endogenous human YAP/TAZ-TEAD cells", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "YAP/TAZ are TEAD-recruited clients and inhibitor effects depend on VGLL4.", "what_it_does_not_show": "Interaction loss explains disappearance; endogenous morphology does not independently isolate phase state.", "confounders_present": [ "Interaction loss explains disappearance; endogenous morphology does not independently isolate phase state." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 33, "pmid": "41832971", "title": "Phase separation of DUX family proteins drives totipotent-like state via 3D genome reorganization and retrotransposon activation.", "citation": "Gao L, Gao Q, Hai N et al. Phase separation of DUX family proteins drives totipotent-like state via 3D genome reorganization and retrotransposon activation. Protein & cell. 2026.", "doi": "10.1093/procel/pwag014", "pmcid": "PMC13521275", "url": "https://pubmed.ncbi.nlm.nih.gov/41832971/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41832971/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID41832971", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "DUX/Dux4 ectopic cells and developmental models", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Homeobox-IDR interactions assemble coactivators and influence target transcription and developmental phenotypes.", "what_it_does_not_show": "R70A and homeobox changes may alter DNA or partner binding; phase-specific necessity at native concentrations is unresolved.", "confounders_present": [ "R70A and homeobox changes may alter DNA or partner binding; phase-specific necessity at native concentrations is unresolved." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 34, "pmid": "38784009", "title": "YAP condensates are highly organized hubs.", "citation": "Hao S, Lee YJ, Benhamou Goldfajn N et al. YAP condensates are highly organized hubs. iScience. 2024.", "doi": "10.1016/j.isci.2024.109927", "pmcid": "PMC11111833", "url": "https://pubmed.ncbi.nlm.nih.gov/38784009/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38784009/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID41550760" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID38784009", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "Endogenous YAP cell imaging and mechanics perturbations", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Hippo signaling and nuclear mechanics regulate YAP hubs containing TEAD and BRD4.", "what_it_does_not_show": "Puncta and slow diffusion do not diagnose LLPS; upstream mechanics and binding change together; linked erratum body not examined.", "confounders_present": [ "Puncta and slow diffusion do not diagnose LLPS; upstream mechanics and binding change together; linked erratum body not examined." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 35, "pmid": "39363017", "title": "Context transcription factors establish cooperative environments and mediate enhancer communication.", "citation": "Kribelbauer-Swietek JF, Pushkarev O, Gardeux V et al. Context transcription factors establish cooperative environments and mediate enhancer communication. Nature genetics. 2024.", "doi": "10.1038/s41588-024-01892-7", "pmcid": "PMC11525195", "url": "https://pubmed.ncbi.nlm.nih.gov/39363017/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39363017/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID39363017", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "Human endogenous enhancers and synthetic reporters", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Distinct TF classes depend on local enhancer context and respond differently to bromodomain inhibition.", "what_it_does_not_show": "Causal enhancer syntax is shown; liquid-state necessity is not measured and condensates remain one possible implementation.", "confounders_present": [ "Causal enhancer syntax is shown; liquid-state necessity is not measured and condensates remain one possible implementation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 36, "pmid": "35963432", "title": "Phase-separation antagonists potently inhibit transcription and broadly increase nucleosome density.", "citation": "Meduri R, Rubio LS, Mohajan S et al. Phase-separation antagonists potently inhibit transcription and broadly increase nucleosome density. The Journal of biological chemistry. 2022.", "doi": "10.1016/j.jbc.2022.102365", "pmcid": "PMC9486037", "url": "https://pubmed.ncbi.nlm.nih.gov/35963432/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35963432/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID35963432", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "Yeast acute alcohol perturbations", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Both 1,6- and 2,5-hexanediol suppress coalescing and noncoalescing gene transcription and alter histone occupancy.", "what_it_does_not_show": "Alcohol is pleiotropic and 2,5-hexanediol is not a reliable inert negative control; result does not exclude specific condensate functions.", "confounders_present": [ "Alcohol is pleiotropic and 2,5-hexanediol is not a reliable inert negative control; result does not exclude specific condensate functions." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 37, "pmid": "41693617", "title": "GATA1 Drives Human Erythropoiesis via Liquid-Liquid Phase Separation.", "citation": "Li M, Gong H, Wen C et al. GATA1 Drives Human Erythropoiesis via Liquid-Liquid Phase Separation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2026.", "doi": "10.1096/fj.202503628R", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/41693617/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41693617/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID41693617", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "GATA1 variants and erythroid differentiation", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "IDR2 variants impair puncta, transcription and erythroid differentiation.", "what_it_does_not_show": "The same variants disrupt chromatin occupancy and FOG1/LMO2 assembly, precluding a phase-only inference.", "confounders_present": [ "The same variants disrupt chromatin occupancy and FOG1/LMO2 assembly, precluding a phase-only inference." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 38, "pmid": "33608942", "title": "RNA polymerase II condensate formation and association with Cajal and histone locus bodies in living human cells.", "citation": "Imada T, Shimi T, Kaiho A et al. RNA polymerase II condensate formation and association with Cajal and histone locus bodies in living human cells. Genes to cells : devoted to molecular & cellular mechanisms. 2021.", "doi": "10.1111/gtc.12840", "pmcid": "PMC8252594", "url": "https://pubmed.ncbi.nlm.nih.gov/33608942/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33608942/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID33608942", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Weak", "system": "HCT116 Pol II imaging and coilin knockout", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Pol II clusters associate with histone locus bodies during S phase.", "what_it_does_not_show": "Coilin loss preserves key clustering kinetics; FRAP and alcohol sensitivity do not establish LLPS or its causal necessity.", "confounders_present": [ "Coilin loss preserves key clustering kinetics; FRAP and alcohol sensitivity do not establish LLPS or its causal necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 39, "pmid": "38127982", "title": "Mammalian circadian clock proteins form dynamic interacting microbodies distinct from phase separation.", "citation": "Xie P, Xie X, Ye C et al. Mammalian circadian clock proteins form dynamic interacting microbodies distinct from phase separation. Proceedings of the National Academy of Sciences of the United States of America. 2023.", "doi": "10.1073/pnas.2318274120", "pmcid": "PMC10756265", "url": "https://pubmed.ncbi.nlm.nih.gov/38127982/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38127982/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID37961341" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID38127982", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "Endogenous PER2 in human cells and mice", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Native circadian PER2 assemblies differ from overexpression-induced liquid condensates and resist several liquid-state probes.", "what_it_does_not_show": "PER2 negative-feedback assemblies are not the same as positive-limb BMAL1 hubs; this is not a universal clock-protein negative result.", "confounders_present": [ "PER2 negative-feedback assemblies are not the same as positive-limb BMAL1 hubs; this is not a universal clock-protein negative result." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [ "Updates37961341 preprint, excluded." ] }, { "n": 40, "pmid": "40119729", "title": "Spuriously transcribed RNAs from CRISPR-sgRNA expression plasmids scaffold biomolecular condensate formation and hamper accurate genomic imaging.", "citation": "Mao S, Wu R, Luo W et al. Spuriously transcribed RNAs from CRISPR-sgRNA expression plasmids scaffold biomolecular condensate formation and hamper accurate genomic imaging. Nucleic acids research. 2025.", "doi": "10.1093/nar/gkaf192", "pmcid": "PMC11928936", "url": "https://pubmed.ncbi.nlm.nih.gov/40119729/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40119729/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID40119729", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "Live-cell RNA imaging vector controls", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Cryptic plasmid-backbone transcripts generate misleading liquid-like structures and paraspeckle protein recruitment.", "what_it_does_not_show": "A method-specific artifact does not explain every native transcription hub; RNA scaffold controls are essential.", "confounders_present": [ "A method-specific artifact does not explain every native transcription hub; RNA scaffold controls are essential." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 41, "pmid": "30500535", "title": "Liquid Nuclear Condensates Mechanically Sense and Restructure the Genome.", "citation": "Shin Y, Chang YC, Lee DSW et al. Liquid Nuclear Condensates Mechanically Sense and Restructure the Genome. Cell. 2018.", "doi": "10.1016/j.cell.2018.10.057", "pmcid": "PMC6724728", "url": "https://pubmed.ncbi.nlm.nih.gov/30500535/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30500535/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID30849377" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID30500535", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "Engineered optogenetic CasDrop cells", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Light-induced IDP droplets restructure chromatin and connect genomic targets.", "what_it_does_not_show": "Engineered concentration and scaffolding establish capacity rather than endogenous regulatory necessity; correction linked but not body-audited.", "confounders_present": [ "Engineered concentration and scaffolding establish capacity rather than endogenous regulatory necessity; correction linked but not body-audited." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 42, "pmid": "33055158", "title": "Transcriptional suppression of ribosomal DNA with phase separation.", "citation": "Ide S, Imai R, Ochi H et al. Transcriptional suppression of ribosomal DNA with phase separation. Science advances. 2020.", "doi": "10.1126/sciadv.abb5953", "pmcid": "PMC7556839", "url": "https://pubmed.ncbi.nlm.nih.gov/33055158/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33055158/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID33055158", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "Mammalian nucleolar Pol I and mutant/inhibitor comparisons", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Condensation-associated inactive caps exclude initiation factors and suppress transcription.", "what_it_does_not_show": "Pol I differs from Pol II; condensates may activate or inhibit depending on composition and reaction stage.", "confounders_present": [ "Pol I differs from Pol II; condensates may activate or inhibit depending on composition and reaction stage." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 43, "pmid": "41028835", "title": "Phase-separated NDF-FACT condensates facilitate transcription elongation on chromatin.", "citation": "Li Z, Burgos-Bravo F, Xu K et al. Phase-separated NDF-FACT condensates facilitate transcription elongation on chromatin. Nature cell biology. 2025.", "doi": "10.1038/s41556-025-01778-8", "pmcid": "PMC12611769", "url": "https://pubmed.ncbi.nlm.nih.gov/41028835/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41028835/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID41028835", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "Reconstituted NDF-FACT and human stem cells", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "NDF-FACT promotes rapid nucleosomal elongation and loss of NDF impairs transcription and differentiation.", "what_it_does_not_show": "Protein loss also removes biochemical chaperone interactions; a phase-specific matched rescue is not established by the examined abstract.", "confounders_present": [ "Protein loss also removes biochemical chaperone interactions; a phase-specific matched rescue is not established by the examined abstract." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 44, "pmid": "35483357", "title": "Tuning levels of low-complexity domain interactions to modulate endogenous oncogenic transcription.", "citation": "Chong S, Graham TGW, Dugast-Darzacq C et al. Tuning levels of low-complexity domain interactions to modulate endogenous oncogenic transcription. Molecular cell. 2022.", "doi": "10.1016/j.molcel.2022.04.007", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/35483357/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35483357/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "EWS-native-hub-programme-followup", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "EWS-FLI1 endogenous targets and engineered interaction variants", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Excess self-association toward macroscopic LLPS represses target transcription and transformation.", "what_it_does_not_show": "Variants change localization and interaction chemistry; does not eliminate a role for small native hubs.", "confounders_present": [ "Variants change localization and interaction chemistry; does not eliminate a role for small native hubs." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [ "Related EWS-FLI1 multivalency programme and native target genes; follows29930090, not an independent assay-class replication." ] }, { "n": 45, "pmid": "33674598", "title": "Loci-specific phase separation of FET fusion oncoproteins promotes gene transcription.", "citation": "Zuo L, Zhang G, Massett M et al. Loci-specific phase separation of FET fusion oncoproteins promotes gene transcription. Nature communications. 2021.", "doi": "10.1038/s41467-021-21690-7", "pmcid": "PMC7935978", "url": "https://pubmed.ncbi.nlm.nih.gov/33674598/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33674598/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID33674598", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "Reconstituted FET fusion proteins and single-molecule DNA assays", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "DNA density and fusion domains support condensate formation and Pol II recruitment.", "what_it_does_not_show": "Fusion and DNA scaffold conditions do not establish native phase-only necessity.", "confounders_present": [ "Fusion and DNA scaffold conditions do not establish native phase-only necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 46, "pmid": "34018649", "title": "FUS oncofusion protein condensates recruit mSWI/SNF chromatin remodeler via heterotypic interactions between prion-like domains.", "citation": "Davis RB, Kaur T, Moosa MM et al. FUS oncofusion protein condensates recruit mSWI/SNF chromatin remodeler via heterotypic interactions between prion-like domains. Protein science : a publication of the Protein Society. 2021.", "doi": "10.1002/pro.4127", "pmcid": "PMC8197437", "url": "https://pubmed.ncbi.nlm.nih.gov/34018649/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34018649/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID34018649", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "Reconstituted FUS-DDIT3 and DNA force/fluorescence assays", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Fusion assemblies recruit SWI/SNF through the disordered domain.", "what_it_does_not_show": "Partner binding and assembly are coupled; oncogenic fusion capacity is not a general transcription principle.", "confounders_present": [ "Partner binding and assembly are coupled; oncogenic fusion capacity is not a general transcription principle." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 47, "pmid": "33523844", "title": "Liquid-liquid phase separation of light-inducible transcription factors increases transcription activation in mammalian cells and mice.", "citation": "Schneider N, Wieland FG, Kong D et al. Liquid-liquid phase separation of light-inducible transcription factors increases transcription activation in mammalian cells and mice. Science advances. 2021.", "doi": "10.1126/sciadv.abd3568", "pmcid": "PMC7775772", "url": "https://pubmed.ncbi.nlm.nih.gov/33523844/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33523844/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID33523844", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "Synthetic optogenetic TFs in cells and mouse transfection", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Engineered condensate-forming TFs increase reporter output.", "what_it_does_not_show": "Synthetic delivery and expression establish engineered sufficiency, not endogenous necessity.", "confounders_present": [ "Synthetic delivery and expression establish engineered sufficiency, not endogenous necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 48, "pmid": "42417395", "title": "Dynamic Regulation of Endogenous Transcription Factor Hubs at Single-Molecule Resolution.", "citation": "Yoshida S, Zhong Y, Kumagai A et al. Dynamic Regulation of Endogenous Transcription Factor Hubs at Single-Molecule Resolution. Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2026.", "doi": "10.1002/advs.202600048", "pmcid": "PMC13343610", "url": "https://pubmed.ncbi.nlm.nih.gov/42417395/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42417395/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID41659683" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "EWS-native-hub-programme-2026", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph0, 1:Results:paragraph2, 1:Results:paragraph8, 1:Results:paragraph9, 1:Results:paragraph12, 1:Results:paragraph20, 1:Results:paragraph22, 1:Results:paragraph29. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "Endogenous CRISPR-tagged EWS-FLI1 single-molecule imaging", "decisive_perturbation": true, "endogenous": true, "direction": "contradicts", "what_it_shows": "Endogenous EWS-FLI1 forms sub-diffraction hubs larger than parental puncta; a fitted nucleation/dissolution model explains the stable size distribution without macroscopic droplets.", "what_it_does_not_show": "Estimated dissolution rate and supersaturation are model-dependent, not directly observed thermodynamic equilibrium; drugs also alter signaling, DNA binding or localization and RNA effects have alternatives.", "confounders_present": [ "Estimated dissolution rate and supersaturation are model-dependent, not directly observed thermodynamic equilibrium; drugs also alter signaling, DNA binding or localization and RNA effects have alternatives." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [ "Previously established A673 Halo knock-in from29930090; new super-resolution analysis but shared label and cellular lineage. Updates41659683 preprint, not counted separately." ] }, { "n": 49, "pmid": "42062246", "title": "BMAL1 regulates circadian rhythms via phase separation-mediated transcriptional hub formation.", "citation": "Gao W, Zhu L, Wei Y et al. BMAL1 regulates circadian rhythms via phase separation-mediated transcriptional hub formation. Signal transduction and targeted therapy. 2026.", "doi": "10.1038/s41392-026-02711-7", "pmcid": "PMC13133405", "url": "https://pubmed.ncbi.nlm.nih.gov/42062246/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42062246/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID42062246", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "BMAL1 cell rescue and SCN mouse behavioral rescue", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "An N-terminal IDR supports circadian complexes and rescue of cellular and behavioral rhythms.", "what_it_does_not_show": "IDR deletion changes partner recruitment as well as condensation; phase-only necessity and universal relevance remain unresolved.", "confounders_present": [ "IDR deletion changes partner recruitment as well as condensation; phase-only necessity and universal relevance remain unresolved." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 50, "pmid": "34163069", "title": "Phase separation drives aberrant chromatin looping and cancer development.", "citation": "Ahn JH, Davis ES, Daugird TA et al. Phase separation drives aberrant chromatin looping and cancer development. Nature. 2021.", "doi": "10.1038/s41586-021-03662-5", "pmcid": "PMC8647409", "url": "https://pubmed.ncbi.nlm.nih.gov/34163069/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34163069/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID34163069", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "NUP98-HOXA9 fusion variants and transformation assays", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "FG-rich IDRs support fusion-driven binding, looping and transformation; FUS IDR replacement rescues.", "what_it_does_not_show": "Ectopic oncogenic fusion and multivalent binding are coupled; native broad primacy is not tested.", "confounders_present": [ "Ectopic oncogenic fusion and multivalent binding are coupled; native broad primacy is not tested." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 51, "pmid": "36309135", "title": "SOX2 Modulates the Nuclear Organization and Transcriptional Activity of the Glucocorticoid Receptor.", "citation": "Stortz M, Oses C, Vázquez Echegaray C et al. SOX2 Modulates the Nuclear Organization and Transcriptional Activity of the Glucocorticoid Receptor. Journal of molecular biology. 2022.", "doi": "10.1016/j.jmb.2022.167869", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36309135/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36309135/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID36309135", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "Ectopic SOX2 and glucocorticoid receptor cells", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "SOX2 changes GR condensates and DNA occupancy through indirect partner effects.", "what_it_does_not_show": "Expression perturbation and DNA binding change simultaneously; GR N-terminal domain is dispensable in this setting.", "confounders_present": [ "Expression perturbation and DNA binding change simultaneously; GR N-terminal domain is dispensable in this setting." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 52, "pmid": "40394324", "title": "Nuclear SREBP2 condensates regulate the transcriptional activation of lipogenic genes and cholesterol homeostasis.", "citation": "Xu M, Jiang SY, Tang S et al. Nuclear SREBP2 condensates regulate the transcriptional activation of lipogenic genes and cholesterol homeostasis. Nature metabolism. 2025.", "doi": "10.1038/s42255-025-01291-0", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40394324/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40394324/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID40394324", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "SREBP2 variants, IDR rescue and male knock-in mice", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Aromatic-IDR mutation reduces output and feeding-induced cholesterol responses; FUS replacement rescues cellular function.", "what_it_does_not_show": "Activation affinity and phase propensity covary; sex and metabolic context limit generalization and the examined abstract does not isolate phase alone.", "confounders_present": [ "Activation affinity and phase propensity covary; sex and metabolic context limit generalization and the examined abstract does not isolate phase alone." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 53, "pmid": "31038454", "title": "Evidence for DNA-mediated nuclear compartmentalization distinct from phase separation.", "citation": "McSwiggen DT, Hansen AS, Teves SS et al. Evidence for DNA-mediated nuclear compartmentalization distinct from phase separation. eLife. 2019.", "doi": "10.7554/eLife.47098", "pmcid": "PMC6522219", "url": "https://pubmed.ncbi.nlm.nih.gov/31038454/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31038454/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID31038454", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "Viral replication compartments and Pol II single-molecule diffusion", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Accessible DNA rebinding explains Pol II accumulation with unrestricted diffusion across compartment boundaries.", "what_it_does_not_show": "A viral compartment is not a normal enhancer; demonstrates a viable non-LLPS mechanism rather than excluding all native LLPS.", "confounders_present": [ "A viral compartment is not a normal enhancer; demonstrates a viable non-LLPS mechanism rather than excluding all native LLPS." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 54, "pmid": "30127355", "title": "RNA polymerase II clustering through carboxy-terminal domain phase separation.", "citation": "Boehning M, Dugast-Darzacq C, Rankovic M et al. RNA polymerase II clustering through carboxy-terminal domain phase separation. Nature structural & molecular biology. 2018.", "doi": "10.1038/s41594-018-0112-y", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30127355/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30127355/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID30127355", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "Human Pol II CTD variants and reconstitution", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "CTD length changes clustering and chromatin association; phosphorylation dissolves in-vitro assemblies.", "what_it_does_not_show": "CTD repeats also recruit essential transcription proteins; clustering and chemistry are not independently varied.", "confounders_present": [ "CTD repeats also recruit essential transcription proteins; clustering and chemistry are not independently varied." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 55, "pmid": "41957181", "title": "Histone acetylation-dependent clustering of BRD2 instructs transcription dynamics.", "citation": "Erdogdu NU, Guhathakurta S, Oellers R et al. Histone acetylation-dependent clustering of BRD2 instructs transcription dynamics. Nature genetics. 2026.", "doi": "10.1038/s41588-026-02533-x", "pmcid": "PMC13083254", "url": "https://pubmed.ncbi.nlm.nih.gov/41957181/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41957181/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID41957181", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "Rapid BRD2 perturbation and Pol II recruitment", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "BRD2 and its IDR support TFIID-associated Pol II recruitment and transcription.", "what_it_does_not_show": "Chromatin binding, acetylation and direct recruitment change together; a phase-specific matched rescue is not established.", "confounders_present": [ "Chromatin binding, acetylation and direct recruitment change together; a phase-specific matched rescue is not established." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 56, "pmid": "27138339", "title": "RNA Polymerase II cluster dynamics predict mRNA output in living cells.", "citation": "Cho WK, Jayanth N, English BP et al. RNA Polymerase II cluster dynamics predict mRNA output in living cells. eLife. 2016.", "doi": "10.7554/eLife.13617", "pmcid": "PMC4929003", "url": "https://pubmed.ncbi.nlm.nih.gov/27138339/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27138339/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PolII-live-cluster-platform-beta-actin", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "Endogenous beta-actin live Pol II clusters", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Brief Pol II cluster lifetimes correlate with stimulated transcription.", "what_it_does_not_show": "Temporal correlation and crowding do not diagnose LLPS or prove phase-state necessity.", "confounders_present": [ "Temporal correlation and crowding do not diagnose LLPS or prove phase-state necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 57, "pmid": "33814344", "title": "1,6-Hexanediol, commonly used to dissolve liquid-liquid phase separated condensates, directly impairs kinase and phosphatase activities.", "citation": "Düster R, Kaltheuner IH, Schmitz M et al. 1,6-Hexanediol, commonly used to dissolve liquid-liquid phase separated condensates, directly impairs kinase and phosphatase activities. The Journal of biological chemistry. 2021.", "doi": "10.1016/j.jbc.2021.100260", "pmcid": "PMC7948595", "url": "https://pubmed.ncbi.nlm.nih.gov/33814344/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33814344/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID33814344", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "Purified enzyme controls", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Hexanediol directly inhibits kinases and phosphatases at concentrations used in phase experiments.", "what_it_does_not_show": "In-vitro enzyme tests expose nonspecificity but do not directly measure every cellular phase mechanism.", "confounders_present": [ "In-vitro enzyme tests expose nonspecificity but do not directly measure every cellular phase mechanism." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 58, "pmid": "34569155", "title": "RNA polymerase II clusters form in line with surface condensation on regulatory chromatin.", "citation": "Pancholi A, Klingberg T, Zhang W et al. RNA polymerase II clusters form in line with surface condensation on regulatory chromatin. Molecular systems biology. 2021.", "doi": "10.15252/msb.202110272", "pmcid": "PMC8474054", "url": "https://pubmed.ncbi.nlm.nih.gov/34569155/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34569155/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID34569155", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "Zebrafish live imaging, modeling and chemical perturbation", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Regulatory chromatin surfaces explain Pol II cluster shapes below bulk LLPS thresholds.", "what_it_does_not_show": "Surface condensation differs from bulk liquid droplets; chemical perturbation and fitted models do not isolate native phase necessity.", "confounders_present": [ "Surface condensation differs from bulk liquid droplets; chemical perturbation and fitted models do not isolate native phase necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 59, "pmid": "38799575", "title": "N-terminal tagging of RNA Polymerase II shapes transcriptomes more than C-terminal alterations.", "citation": "Callan-Sidat A, Zewdu E, Cavallaro M et al. N-terminal tagging of RNA Polymerase II shapes transcriptomes more than C-terminal alterations. iScience. 2024.", "doi": "10.1016/j.isci.2024.109914", "pmcid": "PMC11126984", "url": "https://pubmed.ncbi.nlm.nih.gov/38799575/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38799575/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID38799575", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "Mammalian Pol II tags and CTD variants with single-cell RNA profiles", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Tags cause larger transcriptome changes than CTD alterations; global bursting is largely robust to CTD changes.", "what_it_does_not_show": "Gene-specific CTD dependence remains; tagging artifacts require explicit controls.", "confounders_present": [ "Gene-specific CTD dependence remains; tagging artifacts require explicit controls." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 60, "pmid": "23828889", "title": "Real-time dynamics of RNA polymerase II clustering in live human cells.", "citation": "Cisse II, Izeddin I, Causse SZ et al. Real-time dynamics of RNA polymerase II clustering in live human cells. Science (New York, N.Y.). 2013.", "doi": "10.1126/science.1239053", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/23828889/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/23828889/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PolII-live-cluster-platform", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Weak", "system": "Live human Pol II single-molecule imaging", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Clusters are transient and stimulus-responsive rather than static factories.", "what_it_does_not_show": "Crowding and dynamics alone do not establish liquid-state identity or causal transcription dependence.", "confounders_present": [ "Crowding and dynamics alone do not establish liquid-state identity or causal transcription dependence." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 61, "pmid": "38548891", "title": "Disordered C-terminal domain drives spatiotemporal confinement of RNAPII to enhance search for chromatin targets.", "citation": "Ling YH, Ye Z, Liang C et al. Disordered C-terminal domain drives spatiotemporal confinement of RNAPII to enhance search for chromatin targets. Nature cell biology. 2024.", "doi": "10.1038/s41556-024-01382-2", "pmcid": "PMC11210292", "url": "https://pubmed.ncbi.nlm.nih.gov/38548891/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38548891/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID37577667" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID38548891", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "Living yeast Pol II CTD truncations and single-molecule tracking", "decisive_perturbation": true, "endogenous": true, "direction": "contradicts", "what_it_shows": "CTD-dependent confinement improves target search and bursting without apparent phase-separated condensates.", "what_it_does_not_show": "CTD truncation also changes protein interactions; absence of visible droplets does not exclude nanoscale cooperativity.", "confounders_present": [ "CTD truncation also changes protein interactions; absence of visible droplets does not exclude nanoscale cooperativity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [ "Updates37577667 preprint, excluded." ] }, { "n": 62, "pmid": "37738977", "title": "Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions.", "citation": "Chen L, Zhang Z, Han Q et al. Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions. Molecular cell. 2023.", "doi": "10.1016/j.molcel.2023.08.027", "pmcid": "PMC10592010", "url": "https://pubmed.ncbi.nlm.nih.gov/37738977/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37738977/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID37738977", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "Androgen receptor interaction variants and IDR swaps", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "An optimal interaction range supports enhancer assembly and output; too little or too much is detrimental.", "what_it_does_not_show": "Heterotypic partner binding covaries with condensation; this does not show more LLPS causes more transcription.", "confounders_present": [ "Heterotypic partner binding covaries with condensation; this does not show more LLPS causes more transcription." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 63, "pmid": "42106138", "title": "Intrinsically disordered bHLH family member TCF4 drives phase separation in a DNA-dependent manner.", "citation": "Sozańska N, Klepka BP, Niedzwiecka A et al. Intrinsically disordered bHLH family member TCF4 drives phase separation in a DNA-dependent manner. Archives of biochemistry and biophysics. 2026.", "doi": "10.1016/j.abb.2026.110829", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42106138/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42106138/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID42106138", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Weak", "system": "Purified TCF4 brain isoform and DNA titration", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "TCF4 phase separates in vitro but specific and nonspecific DNA dissolve the droplets.", "what_it_does_not_show": "No endogenous transcription necessity test; isoforms and crowding conditions limit interpretation.", "confounders_present": [ "No endogenous transcription necessity test; isoforms and crowding conditions limit interpretation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 64, "pmid": "40614721", "title": "Reconciling competing models on the roles of condensates and soluble complexes in transcription factor function.", "citation": "Bremer A, Lang WH, Kempen RP et al. Reconciling competing models on the roles of condensates and soluble complexes in transcription factor function. Molecular cell. 2025.", "doi": "10.1016/j.molcel.2025.06.008", "pmcid": "PMC12233198", "url": "https://pubmed.ncbi.nlm.nih.gov/40614721/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40614721/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID39605529" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID40614721", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:RESULTS:paragraph9, 1:RESULTS:paragraph11, 1:RESULTS:paragraph19, 1:RESULTS:paragraph23, 1:RESULTS:paragraph26, 1:RESULTS:paragraph27. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "Yeast Gcn4 variants, biophysical affinity and native promoter assays", "decisive_perturbation": true, "endogenous": true, "direction": "contradicts", "what_it_shows": "Soluble-complex affinity and phase propensity covary; high-affinity variants show condensation-associated attenuation.", "what_it_does_not_show": "Cellular phase assignment partly rests on predictive relationships and ChIP access may differ; neither all-soluble nor all-condensate models are established.", "confounders_present": [ "Cellular phase assignment partly rests on predictive relationships and ChIP access may differ; neither all-soluble nor all-condensate models are established." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [ "Updates39605529 preprint, excluded." ] } ], "verification_summary": { "load_bearing_claims_checked": 68, "verified": 68, "unverified": 0, "contradicted": 0, "note": "Verified attribution is distinct from mechanism truth or complete body access." }, "factual_issues_found": [], "cap_rules_applied": [ { "subclaim_id": "SC1", "cap": "Γ", "cap_source": "rubric", "triggered": true, "trigger_text_quoted": "Mechanistic plausibility plus in vitro reconstitution or simplified cellular support caps at Γ.", "specific_trigger": "Purified proteins and engineered systems phase separate, and native MYOCD, EWS and coactivators form measurable assemblies. Surface condensation, small DNA-bound networks and fitted nonequilibrium nucleation remain distinct alternatives to bona fide endogenous LLPS.", "resulting_ceiling": "Γ" }, { "subclaim_id": "SC2", "cap": "Γ", "cap_source": "rubric", "triggered": true, "trigger_text_quoted": "Mechanistic plausibility plus in vitro reconstitution or simplified cellular support caps at Γ.", "specific_trigger": "MYOCD and NELF preserve important occupancy/localization controls and use unrelated IDR rescue; these establish meaningful assembly contributions. CDT1 condensation without function and coupled cofactor affinity show that liquid state alone is not isolated. MYC phase switching demonstrates restricted engineered effects, not native global necessity.", "resulting_ceiling": "Γ" }, { "subclaim_id": "SC3", "cap": "Γ", "cap_source": "rubric", "triggered": true, "trigger_text_quoted": "Mechanistic plausibility plus in vitro reconstitution or simplified cellular support caps at Γ.", "specific_trigger": "Native hubs without macroscopic LLPS, yeast CTD confinement, largely phase-insensitive MYC output and inhibitory droplets constrain universal primacy. Selected positive contexts do not dominate all competent biochemical recruitment models.", "resulting_ceiling": "Γ" } ], "cap_precedence_resolutions": [ { "collision": "Perturbation in a defined setting versus broader inference", "subclaim_scope_cap_binds_on": "Endogenous transcriptional machinery forms liquid-liquid phase-separated condensates whose liquid state is required for transcription and is its primary organizing principle.", "subclaim_scope_threshold_binds_on": "The precise experimentally tested subclaim scope", "resolution": "Puncta/FRAP, in-vitro phase and reporter-only behavior cannot establish native liquid-state necessity. Positive native rescue sets are assessed jointly rather than dismissed one by one: they narrow abundance, localization and occupancy errors, but do not remove the shared affinity/composition alternative. Scoped assembly-model thresholds therefore do not lift the stricter phase-state claim.", "note": "Convergent lines are assessed as a set; one weak leg is not re-capped over the assembled case." } ], "boundary_check_BGD": [ { "subclaim_id": "SC1", "field_valid_perturbation_quote": "\n- Endogenous degron of a condensate component with matched rescue, AND evidence that the specific condensate state (not generic protein loss) drives the phenotype\n- Locus-specific disruption of looping with locus-specific effect\n- Combinatorial histone-mark perturbation showing direct output dependence\n- Critically: specificity against cell-cycle collapse, global transcriptional collapse, and replication stress must be demonstrated", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Native concentration does not by itself identify a thermodynamic liquid phase." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Purified proteins and engineered systems phase separate, and native MYOCD, EWS and coactivators form measurable assemblies. Surface condensation, small DNA-bound networks and fitted nonequilibrium nucleation remain distinct alternatives to bona fide endogenous LLPS.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC2", "field_valid_perturbation_quote": "\n- Endogenous degron of a condensate component with matched rescue, AND evidence that the specific condensate state (not generic protein loss) drives the phenotype\n- Locus-specific disruption of looping with locus-specific effect\n- Combinatorial histone-mark perturbation showing direct output dependence\n- Critically: specificity against cell-cycle collapse, global transcriptional collapse, and replication stress must be demonstrated", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Preserved basal occupancy narrows loss-of-binding but does not match cofactor affinity under every active condition." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "MYOCD and NELF preserve important occupancy/localization controls and use unrelated IDR rescue; these establish meaningful assembly contributions. CDT1 condensation without function and coupled cofactor affinity show that liquid state alone is not isolated. MYC phase switching demonstrates restricted engineered effects, not native global necessity.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC3", "field_valid_perturbation_quote": "\n- Endogenous degron of a condensate component with matched rescue, AND evidence that the specific condensate state (not generic protein loss) drives the phenotype\n- Locus-specific disruption of looping with locus-specific effect\n- Combinatorial histone-mark perturbation showing direct output dependence\n- Critically: specificity against cell-cycle collapse, global transcriptional collapse, and replication stress must be demonstrated", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Selected reporter or oncogenic fusion effects do not establish representative active-locus primacy." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Native hubs without macroscopic LLPS, yeast CTD confinement, largely phase-insensitive MYC output and inhibitory droplets constrain universal primacy. Selected positive contexts do not dominate all competent biochemical recruitment models.", "ceiling_from_boundary_check": "Γ" } ], "thresholds_tested": [ { "subclaim_id": "SC1", "threshold": "Δ", "requirement_quoted": "Requires at least one endogenous perturbation showing the proposed feature contributes causally to the claimed output.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Native concentration titration and orthogonal quantitative state measurements distinguishing LLPS, chromatin binding, surface condensation and arrested network growth." }, { "subclaim_id": "SC2", "threshold": "Δ", "requirement_quoted": "Requires at least one endogenous perturbation showing the proposed feature contributes causally to the claimed output.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Reversible endogenous state-selective perturbation with matched DNA occupancy, protein abundance and cofactor affinity, plus native nascent-output rescue." }, { "subclaim_id": "SC3", "threshold": "Δ", "requirement_quoted": "Requires at least one endogenous perturbation showing the proposed feature contributes causally to the claimed output.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Representative prespecified loci/lineages with matched biochemical-only and material-state-only perturbations establishing dominant necessity and sufficiency." } ], "generalization_check": { "generalization_tested": "yes", "context_boundary_mapped": "yes", "internal_negative_controls": [ "MYOCD-CDT1 restores condensation and occupancy but fails cofactor recruitment/output; matched construct expression (38489358).", "NELF IDR deletion retains nuclear targeting, complex incorporation and basal promoter binding; stress-upregulated chaperones remain responsive (33548202).", "MYC HOTag-free lenalidomide controls show only10 differentially expressed genes without overlap with phase-sensitive targets (38811792).", "EWS parental endogenous labels and photoblinking correction distinguish neomorphic hub sizes (42417395).", "Hexanediol enzyme controls and both1,6/2,5 yeast alcohols expose nonspecificity (33814344,35963432).", "PolII tag comparisons and cryptic vector-RNA controls expose imaging/transcriptome artifacts (38799575,40119729)." ], "note": "Specify native/engineered abundance, lineage, locus, tag and reaction stage before output. PolI repression, PER2 negative limb and BMAL1 positive limb are distinct systems. Oncogenic fusion results are not universal native TF evidence. No claim that the bounded corpus exhausts all phase-selective studies." }, "falsification_patterns_met": [ { "pattern": "More liquid condensation fails to enhance output", "evidence": "Trojanowski reporter droplets neutral/inhibitory; Chong high self-association inhibits native targets; Bremer high-affinity variants underperform (35537448,35483357,40614721).", "downgrade_applied": false }, { "pattern": "Condensates and occupancy recover but function does not", "evidence": "MYOCD-CDT1 forms condensates and binds DNA more strongly but fails acetylation/reprogramming (38489358).", "downgrade_applied": false }, { "pattern": "Native function without visible LLPS", "evidence": "Endogenous EWS hubs and yeast CTD confinement; engineered diffuse MYC drives most target-gene responses (29930090,42417395,38548891,38811792).", "downgrade_applied": false } ], "pitfalls_flagged": [ { "pitfall": "FRAP or puncta treated as phase diagnosis", "where": "Native hubs, surfaces and diffusion/rebinding are separately interpreted." }, { "pitfall": "Hexanediol treated as selective LLPS loss", "where": "Enzyme inhibition and yeast1,6/2,5 controls retained (33814344,35963432)." }, { "pitfall": "IDR dependence treated as liquid-state dependence", "where": "MYOCD occupancy/CDT1 control and NELF basal binding plus rescue are weighed against cofactor chemistry." }, { "pitfall": "All condensates assumed transcription activating", "where": "NELF repression, PolI caps and inhibitory Gcn4/EWS states retained." }, { "pitfall": "Tag or cryptic RNA artifact ignored", "where": "PolII tagging and vector-backbone controls included (38799575,40119729)." }, { "pitfall": "Small hubs confused with absent molecular assembly", "where": "Negative macroscopic LLPS results do not deny cooperative sub-diffraction networks." }, { "pitfall": "Provider retrieval counts and substituted references treated as validation", "where": "Only two exact original-aspect comparisons credited; canonical dates restored." } ], "causal_tally_audit": { "tally_claimed_by_document": 29, "tally_after_audit": 29, "items_rejected": [ "Null and negative contrasts are discriminators, not positive threshold crossings. Reports and replications are not independent causal lines.", "Discriminator flags include positive and negative contrasts, not independent positive LLPS threshold proofs.", "One original theoretical-model report is marked Weak and nonexperimental; not counted as a perturbation.", "The strongest MYOCD/NELF controls narrow alternatives but do not isolate liquid state across the registered conjunction." ] }, "steelman": { "case_one_rung_higher": "One rung above Γ is Δ: MYOCD occupancy-matched heterologous rescue, NELF basal-binding controls and BRD4 pH-sensor mutants could be interpreted as field-valid causal liquid-state interventions.", "case_one_rung_lower": "One rung below Γ is Β: native puncta and cofactor colocalization could be entirely associative while engineered droplets remain outside the endogenous claim.", "which_rejected": "Δ is rejected for the registered phase-specific conjunction because successful rescue also restores selective partner chemistry and no matched state-only endogenous contrast is established. Β understates demonstrated phase capacity, controlled assembly interventions and measured native concentration. Those contributions earn stronger alternative-model scores without upgrading the LLPS necessity/primacy claims.", "blocking_cap_threshold_or_missing_experiment": "Missing experiment: Reversible native material-state tuning with independently matched binding and cofactor recruitment" }, "final_score": { "hsef_level": "Γ", "hsef_descriptor": "Mechanistically plausible, partial system support", "confidence": "Moderate", "confidence_rationale": "64 primary reports with 10 selected partial-body examinations; density, heterogeneous controls and methodological heterogeneity set the confidence, not correctness and not the reviewer's access depth. Re-tested against the High band text, which requires extensive independent replication across labs, models and assay modalities: the band holds at Moderate.", "rests_on_non_peer_reviewed_work": false, "rationale": "Weakest-link aggregation yields Γ. SC1 has clear physical capacity and native assemblies but incomplete phase diagnosis; SC2 has strong selected assembly/rescue evidence without cleanly isolating liquid state from affinity and composition; SC3 lacks representative native phase-specific primacy. Stronger levels for multivalency models are not transferred to the stricter LLPS conjunction." }, "role_of_mechanism": { "classification": "reinforcing / stabilizing factor", "derivation_step_matched": 5, "derivation": "Step1 is not universal because selected assemblies can precede and alter output. Step2 is exceeded by controlled genetic/engineered contrasts. Step3 fails broad necessity, sufficiency and rate-limiting primary status. Step4 may fit individual assemblies but no general phase-state necessity is established. Step5 describes bounded multivalent stabilization/amplification and composition-dependent repression, assigned before model ranking; it is not proof that bona fide LLPS is universally necessary.", "tournament_used_as_tiebreaker": false, "note": "Derived from causal direction, not tournament rank." }, "extended_scoring_MSD": { "momentum": { "value": "Mechanistic only", "artifact": "The most recent primary perturbation work in this corpus tests mechanism or scope rather than the boundary check: reversible pH control of BRD4 and MED1 assemblies (40680734), the Gcn4 soluble-versus-condensed comparison (40614721) and the 2026 single-molecule measurement of endogenous EWS::FLI1 hubs (42417395). None of them delivers the matched state-only endogenous contrast that the \u0394 threshold requires here. No presently recruiting trial or named pending result is asserted.", "justification": "The most recent primary perturbation work in this corpus tests mechanism or scope rather than the boundary check: reversible pH control of BRD4 and MED1 assemblies (40680734), the Gcn4 soluble-versus-condensed comparison (40614721) and the 2026 single-molecule measurement of endogenous EWS::FLI1 hubs (42417395). None of them delivers the matched state-only endogenous contrast that the \u0394 threshold requires here. No presently recruiting trial or named pending result is asserted." }, "stability": { "value": "Stable", "trigger": "No named pending result is asserted to be likely to move the registered score imminently.", "justification": "No named pending result is asserted to be likely to move the registered score imminently." }, "divergence": { "implied_level": null, "implied_level_basis": "No single field-implied level is defensible from conflicting framings.", "assessed_level": "Γ", "gap_in_rungs": null, "value": "Contested", "justification": "The two framings carry different implied levels, so no single implied level and no arithmetic gap can be stated. Review and press framing of transcriptional condensates as the organizing principle of gene control implies a level well above the assessed \u0393, while a substantial part of the primary literature cited here argues for multivalent hubs and soluble complexes and against liquid-state necessity. No manufactured field consensus is asserted." }, "calibration_note": "M/S/D never modify HSEF level or confidence." }, "change_record": { "applies": false, "prior_level": "Ranking categorical verdict visible; no prior letter used as a target", "prior_confidence": null, "prior_source": null, "derived_before_consulting_prior": false, "new_level": "Γ", "direction": "newly assigned", "what_moved_it": "Fresh primary evidence appraisal; not blinded.", "divergence_from_other_reviewers": null }, "proposed_decisive_experiments": [ { "name": "Registered boundary experiment", "experiment": "Reversible native material-state tuning with independently matched binding and cofactor recruitment", "readout": "Quantitative endogenous state diagnostics, molecule abundance/occupancy, nascent burst rates, elongation and viability in the same prespecified loci/cells.", "critical_control": "Biochemical-only versus state-only mutants with orthogonal matched rescue; tag-free confirmation and alcohol-free perturbation.", "supporting_result": "State-only loss suppresses nascent output despite unchanged chemistry/occupancy and state restoration rescues across independent lineages.", "falsifying_result": "Output follows binding or cofactor chemistry while state changes are neutral or inhibitory, or rescue works without liquid-phase restoration." } ], "knowledge_gaps": [ { "name": "Gap 1", "statement": "Native quantitative discrimination of bulk LLPS, surface condensation, finite hubs and percolated networks.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 2", "statement": "Interaction-matched reversible material-state perturbations preserving protein abundance, DNA occupancy and cofactor affinity.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 3", "statement": "Independent replication of MYOCD/NELF/SREBP2 IDR replacement controls across laboratories and native loci.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 4", "statement": "Same-cell time ordering of hub nucleation, occupancy, cofactor recruitment and nascent transcription.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 5", "statement": "Representative locus panels measuring both positive and inhibitory phase effects without responder-selected scope.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 6", "statement": "Nonlinear concentration and affinity maps reconciling soluble complexes with condensation.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 7", "statement": "Native tag controls, cryptic scaffold-RNA controls and orthogonal state readouts.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 8", "statement": "Phase effects during activation, pausing, elongation, stress repression and cell-cycle transitions separately.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 9", "statement": "Prespecified in vivo sex, lineage and disease-fusion versus normal-TF generalization.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 10", "statement": "Original correction bodies and supplements, unavailable provider target texts and source-substitution audit.", "relevance": "Limits mechanism identification or scope." } ], "review_metadata": { "review_date": "2026-10-08", "reviewer": "Codex", "evidence_base_note": "64 primary reports; literature cutoff 2026-10-08; source examination UTC date 2026-10-09; bounded critical review, not exhaustive systematic review.", "literature_tools_available": true, "literature_tools_note": "Life Sciences Literature PubMed/Entrez; attempted Europe PMC XML and successful public NCBI PMC direct HTTPS access are separately logged. Signed-in Consensus browser discovery and targeted indexed full-text checks are reconciled with original sections; failed matches and source substitutions remain explicit. Zero Consensus API calls. SciSpace discovery was also used; primary leads were resolved to canonical originals before counting. See scispace-discovery.json.", "skill_version": "5.3", "validator_run": "exact archived v5.3 validator 2.3; see validator.txt", "validator_warnings_addressed": "The index entry was restated as the preregistered causal claim. No real phenomenon is labelled refuted; warning is explicitly justified.", "consensus_consistency_audit": "2026-10-09; supplementary provenance/source reconciliation; original grading retained; prior grades visible." }, "is_calibration_entry": { "value": false, "entry_role": "not_calibration", "blind_graded": null, "completed_blinded_calibration": false, "expected_band_sealed_at": "", "target_sha256": "", "target_authorship": "not applicable", "target_author_saw_review": null, "future_run_status": "not prepared", "unblinded_reason": "Ranking categorical verdict and index guidance were visible. No completed blinded calibration claimed." }, "upper_ladder_check": { "final_level_below_zeta": true, "equivalents_considered": [ { "kind": "mendelian_randomization", "available": false, "why_not_sufficient": "Upper levels remain possible. Native IDR replacements, measured abundance, basal promoter controls, acute protein loss and mouse functional phenotypes were considered. These lift bounded assembly models above mere correlation but leave liquid-state specificity unresolved. No impossible clinical RCT is required." }, { "kind": "natural_experiment", "available": false, "why_not_sufficient": "Upper levels remain possible. Native IDR replacements, measured abundance, basal promoter controls, acute protein loss and mouse functional phenotypes were considered. These lift bounded assembly models above mere correlation but leave liquid-state specificity unresolved. No impossible clinical RCT is required." }, { "kind": "dose_response_across_populations", "available": false, "why_not_sufficient": "Upper levels remain possible. Native IDR replacements, measured abundance, basal promoter controls, acute protein loss and mouse functional phenotypes were considered. These lift bounded assembly models above mere correlation but leave liquid-state specificity unresolved. No impossible clinical RCT is required." }, { "kind": "withdrawal_rechallenge", "available": false, "why_not_sufficient": "Upper levels remain possible. Native IDR replacements, measured abundance, basal promoter controls, acute protein loss and mouse functional phenotypes were considered. These lift bounded assembly models above mere correlation but leave liquid-state specificity unresolved. No impossible clinical RCT is required." }, { "kind": "therapeutic_perturbation_hard_endpoint", "available": false, "why_not_sufficient": "Upper levels remain possible. Native IDR replacements, measured abundance, basal promoter controls, acute protein loss and mouse functional phenotypes were considered. These lift bounded assembly models above mere correlation but leave liquid-state specificity unresolved. No impossible clinical RCT is required." } ], "convergence_present": true, "cap_reapplied_to_convergent_set": false }, "provenance_header": { "sources_total": 64, "claims_total": 68, "claims_verified": 68, "claims_unverified": 0, "claims_contradicted": 0, "tier_a_sources": 64, "generated_by": "Codex; HSEF v5.3", "gate_passed": true }, "claims": [ { "id": "C1", "text": "Low RNA promotes and high RNA dissolves electrostatic condensates with transcription feedback. RNA changes binding and transcription chemistry; endogenous phase-selective necessity is not isolated.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 1 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C2", "text": "HOXD13 repeat expansion changes co-condensation and cell-specific developmental transcription. Repeat changes also alter interactions/aggregation; human variant effects do not uniquely attribute liquid state.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 2 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C3", "text": "Mediator and Pol II form dynamic clusters that colocalize and respond to transcription inhibitors. Puncta, dynamics and inhibitor sensitivity do not establish phase boundary or phase-state necessity.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 3 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C4", "text": "m6A-eRNAs recruit YTHDC1/BRD4 and depletion reduces enhancer activation. Reader depletion and IDR/arginine changes also affect RNA/cofactor binding; state specificity remains.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 4 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C5", "text": "Acidic pH disrupts BRD4/MED1 assemblies and changes inflammatory output through histidine-rich regions. Stable protein abundance, isolated nuclei, reversible pH and functional segment mutants narrow generic collapse; protonation affects molecular affinities and phase together. FRAP/alcohol are not specific state diagnoses.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 5 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph7, 1:Results:paragraph12, 1:Results:paragraph13, 1:Results:paragraph14, 1:Results:paragraph15. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C6", "text": "Nearby condensate enhances burst size/frequency while basal output persists when distant; local DNA/cohesin perturbations affect enhancement. Assembly position is not itself liquid diagnosis; DNA/protein perturbations affect other functions. Erratum linked, body audit pending.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 6 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C7", "text": "Matched N-myc levels show phase separation further modulates fewer than three percent of regulated genes with proliferation effects. Engineered state/overexpression and small affected set constrain broad primacy; correction linked, body audit pending.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 7 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:RESULTS:paragraph14, 1:RESULTS:paragraph18, 1:RESULTS:paragraph20, 1:RESULTS:paragraph21, 1:RESULTS:paragraph22, 1:RESULTS:paragraph23. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C8", "text": "Multivalent interactions enhance occupancy/residence/cofactor recruitment; droplets are neutral or inhibitory for output. Reporter and synthetic platform cannot refute all endogenous contexts; it separates assembly benefits from droplet state.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 8 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: Scite body characters 0-8000, Scite body characters 16000-24000, Scite body characters 32000-40000. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C9", "text": "CTD clusters nucleate engineered TAF15 condensates and amplify transcription. Optogenetic concentration and FET interactions establish capacity, not endogenous universal need.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 9 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C10", "text": "TRIM28 degradation shifts assemblies to ERVs; RNA knockdown or TF overexpression rescues localization. TRIM28/RNA/TF changes alter gene regulation directly; condensate relocalization is not selective liquid-state intervention.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 10 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C11", "text": "TF site density/affinity thresholds support cooperative condensation and enhancer output. DNA binding and recruitment share thresholds; phase-specific endogenous output not isolated.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 11 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C12", "text": "CBX2-DNA interactions nucleate assemblies and accelerate repeated target search. DNA binding and rebinding can produce hubs; repression differs from broad active-locus primacy.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 12 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C13", "text": "Aire polymerization, histone binding and coactivator recruitment balance enhancer assemblies and transcription. Controlled polymerization is a network assembly mechanism; liquid demixing and functional specificity are separate.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 13 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C14", "text": "Endogenous MYOCD knock-in differentiation shows hubs at measured native concentrations; matched-expression aromatic IDR replacements rescue reprogramming and preserve DNA occupancy. CDT1 replacement restores condensates and high DNA occupancy but not p300 recruitment, acetylation or output; chemistry and composition matter, while liquid state alone remains unisolated.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 14 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:RESULTS:paragraph4, 1:RESULTS:paragraph6, 1:RESULTS:paragraph14, 1:RESULTS:paragraph18, 1:RESULTS:paragraph19, 1:RESULTS:paragraph22, 1:RESULTS:paragraph25. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C15", "text": "NELF IDR replacement with FUS/EWS supports stress-dependent promoter recruitment and downregulation. Nuclear localization, complex incorporation and basal promoter binding are preserved after IDR deletion; stress-dependent occupancy changes. FUS/EWS replacements constitutively repress and improve survival, but chemical recruitment and material state remain coupled.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 15 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph58, 1:Results:paragraph71. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C16", "text": "Histone tails, H1/linker length and acetylation tune chromatin droplets; acetylated chromatin co-condenses with BRD4. Microinjected/reconstituted polymer capacity is not endogenous active transcription liquid-state necessity.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 16 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C17", "text": "AD-directed optimized compounds reduce AR transcription and tumour effects with target affinity. AD interaction/nuclear entry effects accompany condensation; drug efficacy is not a phase-only perturbation.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 17 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C18", "text": "Signalling-factor IDRs partition with Mediator and beta-catenin occupies selected enhancers through multiple interactions. DNA-binding and cofactor interactions can localize signals without unique phase necessity.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 18 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C19", "text": "Hsf1/Hsp70/IDR mutations alter clusters, intergenic coalescence and fitness. Stress and protein binding changes remain coupled; networked clustering need not diagnose classical isotropic LLPS.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 19 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C20", "text": "Model predicts extrusion-dependent promoter contact probabilities from linker relaxation. Original theoretical research, not empirical phase-state or transcription necessity; assumptions require tests.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 20 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C21", "text": "BRD4/MED1 puncta at super-enhancers, chemical sensitivity and IDR droplets support condensation capacity. Puncta, FRAP, hexanediol and extract compartmentalization cannot isolate endogenous liquid-state necessity.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 21 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 3:Coactivator puncta and super-enhancer occupancy are sensitive to condensate perturbation, 5:MED1-IDR participates in liquid-liquid phase separation in cells, 6:Conserved serine bias in the MED1-IDR is necessary for phase separation, 7:MED1-IDR droplets can incorporate proteins necessary for transcription. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C22", "text": "AD residues jointly control droplet propensity and transcriptional activity. Same residues mediate cofactor affinity; correlated losses do not separate phase from binding.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 22 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C23", "text": "FLI1/ETS DNA-binding domains enhance EWS assembly, whereas DNA binding suppresses these interactions and condensation. Biophysical reconstitution, not native transcription necessity; shows DBD and LCD functions are intertwined.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 23 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C24", "text": "PSPC1 links RNA/Pol II engagement; acute degradation impairs polymerase binding and nascent transcription. PSPC1 RNA binding and polymerase chemistry change with loss; binding-matched phase rescue must be demonstrated.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 24 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C25", "text": "Pol II enters Xist territory; apparent depletion reflects loss of chromatin-bound fraction. Inactive-X initiation context differs from active loci; disproves a proposed diffusion barrier, not every phase assembly.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 25 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C26", "text": "Homotypic/heterotypic interaction changes affect puncta, aberrant transcription and transformation. Oncofusion and ectopic construct scope; interacting residues and chromatin binding must remain matched for LLPS attribution.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 26 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C27", "text": "Patterned charge blocks determine functional partitioning and gene activation during transition. Charge sequence tunes affinity and RNA/protein binding as well as phase; selective liquid property not fully disentangled.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 27 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C28", "text": "YAP assemblies recruit TEAD/TAZ and eventually Pol II; AD deletion suppresses assembly and signalling. Osmotic crowding and activation-domain chemistry accompany assembly; physiological unstressed scope differs.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 28 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C29", "text": "NICD forms transcription assemblies and enhancer loops, with phase separation coupled to percolation model. TAD changes affect activation surfaces; viscoelastic network and classical liquid demixing are distinct propositions. Final replaces preprint39131356.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 29 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph3, 1:Results:paragraph19, 1:Results:paragraph20, 1:Results:paragraph23, 1:Results:paragraph25. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C30", "text": "Dynamic LCD hubs stabilize DNA binding and activate transcription without detectable phase separation at physiological abundance. Native hub interactions are real; lack of detected bulk LLPS cannot exclude subresolution or coupled transitions.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 30 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 4:EWS/FLI1 forms hubs at endogenous GGAA microsatellites, 5:Dynamic EWS LCD-LCD interactions mediate formation of EWS/FLI1 hubs, 6:EWS LCD-LCD interactions are essential for transcription and transformation\nfunctions of EWS/FLI1. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C31", "text": "Post-initiation CTD ablation preserves pause maintenance and productive release. Stage-specific test does not refute CTD initiation function or all phase pathways.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 31 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C32", "text": "YAP/TAZ are TEAD-recruited clients and inhibitor effects depend on VGLL4. Interaction loss explains disappearance; endogenous morphology does not independently isolate phase state.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 32 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C33", "text": "Homeobox-IDR interactions assemble coactivators and influence target transcription and developmental phenotypes. R70A and homeobox changes may alter DNA or partner binding; phase-specific necessity at native concentrations is unresolved.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 33 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C34", "text": "Hippo signaling and nuclear mechanics regulate YAP hubs containing TEAD and BRD4. Puncta and slow diffusion do not diagnose LLPS; upstream mechanics and binding change together; linked erratum body not examined.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 34 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C35", "text": "Distinct TF classes depend on local enhancer context and respond differently to bromodomain inhibition. Causal enhancer syntax is shown; liquid-state necessity is not measured and condensates remain one possible implementation.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 35 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C36", "text": "Both 1,6- and 2,5-hexanediol suppress coalescing and noncoalescing gene transcription and alter histone occupancy. Alcohol is pleiotropic and 2,5-hexanediol is not a reliable inert negative control; result does not exclude specific condensate functions.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 36 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C37", "text": "IDR2 variants impair puncta, transcription and erythroid differentiation. The same variants disrupt chromatin occupancy and FOG1/LMO2 assembly, precluding a phase-only inference.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 37 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C38", "text": "Pol II clusters associate with histone locus bodies during S phase. Coilin loss preserves key clustering kinetics; FRAP and alcohol sensitivity do not establish LLPS or its causal necessity.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 38 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C39", "text": "Native circadian PER2 assemblies differ from overexpression-induced liquid condensates and resist several liquid-state probes. PER2 negative-feedback assemblies are not the same as positive-limb BMAL1 hubs; this is not a universal clock-protein negative result.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 39 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C40", "text": "Cryptic plasmid-backbone transcripts generate misleading liquid-like structures and paraspeckle protein recruitment. A method-specific artifact does not explain every native transcription hub; RNA scaffold controls are essential.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 40 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C41", "text": "Light-induced IDP droplets restructure chromatin and connect genomic targets. Engineered concentration and scaffolding establish capacity rather than endogenous regulatory necessity; correction linked but not body-audited.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 41 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C42", "text": "Condensation-associated inactive caps exclude initiation factors and suppress transcription. Pol I differs from Pol II; condensates may activate or inhibit depending on composition and reaction stage.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 42 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C43", "text": "NDF-FACT promotes rapid nucleosomal elongation and loss of NDF impairs transcription and differentiation. Protein loss also removes biochemical chaperone interactions; a phase-specific matched rescue is not established by the examined abstract.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 43 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C44", "text": "Excess self-association toward macroscopic LLPS represses target transcription and transformation. Variants change localization and interaction chemistry; does not eliminate a role for small native hubs.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 44 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C45", "text": "DNA density and fusion domains support condensate formation and Pol II recruitment. Fusion and DNA scaffold conditions do not establish native phase-only necessity.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 45 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C46", "text": "Fusion assemblies recruit SWI/SNF through the disordered domain. Partner binding and assembly are coupled; oncogenic fusion capacity is not a general transcription principle.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 46 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C47", "text": "Engineered condensate-forming TFs increase reporter output. Synthetic delivery and expression establish engineered sufficiency, not endogenous necessity.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 47 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C48", "text": "Endogenous EWS-FLI1 forms sub-diffraction hubs larger than parental puncta; a fitted nucleation/dissolution model explains the stable size distribution without macroscopic droplets. Estimated dissolution rate and supersaturation are model-dependent, not directly observed thermodynamic equilibrium; drugs also alter signaling, DNA binding or localization and RNA effects have alternatives.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 48 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph0, 1:Results:paragraph2, 1:Results:paragraph8, 1:Results:paragraph9, 1:Results:paragraph12, 1:Results:paragraph20, 1:Results:paragraph22, 1:Results:paragraph29. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C49", "text": "An N-terminal IDR supports circadian complexes and rescue of cellular and behavioral rhythms. IDR deletion changes partner recruitment as well as condensation; phase-only necessity and universal relevance remain unresolved.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 49 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C50", "text": "FG-rich IDRs support fusion-driven binding, looping and transformation; FUS IDR replacement rescues. Ectopic oncogenic fusion and multivalent binding are coupled; native broad primacy is not tested.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 50 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C51", "text": "SOX2 changes GR condensates and DNA occupancy through indirect partner effects. Expression perturbation and DNA binding change simultaneously; GR N-terminal domain is dispensable in this setting.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 51 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C52", "text": "Aromatic-IDR mutation reduces output and feeding-induced cholesterol responses; FUS replacement rescues cellular function. Activation affinity and phase propensity covary; sex and metabolic context limit generalization and the examined abstract does not isolate phase alone.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 52 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C53", "text": "Accessible DNA rebinding explains Pol II accumulation with unrestricted diffusion across compartment boundaries. A viral compartment is not a normal enhancer; demonstrates a viable non-LLPS mechanism rather than excluding all native LLPS.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 53 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C54", "text": "CTD length changes clustering and chromatin association; phosphorylation dissolves in-vitro assemblies. CTD repeats also recruit essential transcription proteins; clustering and chemistry are not independently varied.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 54 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C55", "text": "BRD2 and its IDR support TFIID-associated Pol II recruitment and transcription. Chromatin binding, acetylation and direct recruitment change together; a phase-specific matched rescue is not established.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 55 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C56", "text": "Brief Pol II cluster lifetimes correlate with stimulated transcription. Temporal correlation and crowding do not diagnose LLPS or prove phase-state necessity.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 56 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C57", "text": "Hexanediol directly inhibits kinases and phosphatases at concentrations used in phase experiments. In-vitro enzyme tests expose nonspecificity but do not directly measure every cellular phase mechanism.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 57 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C58", "text": "Regulatory chromatin surfaces explain Pol II cluster shapes below bulk LLPS thresholds. Surface condensation differs from bulk liquid droplets; chemical perturbation and fitted models do not isolate native phase necessity.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 58 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C59", "text": "Tags cause larger transcriptome changes than CTD alterations; global bursting is largely robust to CTD changes. Gene-specific CTD dependence remains; tagging artifacts require explicit controls.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 59 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C60", "text": "Clusters are transient and stimulus-responsive rather than static factories. Crowding and dynamics alone do not establish liquid-state identity or causal transcription dependence.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 60 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C61", "text": "CTD-dependent confinement improves target search and bursting without apparent phase-separated condensates. CTD truncation also changes protein interactions; absence of visible droplets does not exclude nanoscale cooperativity.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 61 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C62", "text": "An optimal interaction range supports enhancer assembly and output; too little or too much is detrimental. Heterotypic partner binding covaries with condensation; this does not show more LLPS causes more transcription.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 62 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C63", "text": "TCF4 phase separates in vitro but specific and nonspecific DNA dissolve the droplets. No endogenous transcription necessity test; isoforms and crowding conditions limit interpretation.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 63 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "C64", "text": "Soluble-complex affinity and phase propensity covary; high-affinity variants show condensation-associated attenuation. Cellular phase assignment partly rests on predictive relationships and ChIP access may differ; neither all-soluble nor all-condensate models are established.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 64 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:RESULTS:paragraph9, 1:RESULTS:paragraph11, 1:RESULTS:paragraph19, 1:RESULTS:paragraph23, 1:RESULTS:paragraph26, 1:RESULTS:paragraph27. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-09", "note": "" }, { "id": "CSC1", "text": "Purified proteins and engineered systems phase separate, and native MYOCD, EWS and coactivators form measurable assemblies. Surface condensation, small DNA-bound networks and fitted nonequilibrium nucleation remain distinct alternatives to bona fide endogenous LLPS.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 32, 33, 34, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-09", "note": "" }, { "id": "CSC2", "text": "MYOCD and NELF preserve important occupancy/localization controls and use unrelated IDR rescue; these establish meaningful assembly contributions. CDT1 condensation without function and coupled cofactor affinity show that liquid state alone is not isolated. MYC phase switching demonstrates restricted engineered effects, not native global necessity.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 41, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 54, 55, 56, 57, 58, 59, 61, 62, 64 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-09", "note": "" }, { "id": "CSC3", "text": "Native hubs without macroscopic LLPS, yeast CTD confinement, largely phase-insensitive MYC output and inhibitory droplets constrain universal primacy. Selected positive contexts do not dominate all competent biochemical recruitment models.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 1, 6, 7, 8, 25, 30, 31, 35, 39, 42, 44, 48, 53, 61, 64 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-09", "note": "" }, { "id": "CH", "text": "Native transcriptional hubs and functional multivalent assemblies are supported; liquid-state-specific necessity and broad organizing primacy remain unestablished.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 14, 15, 7, 8, 64, 30 ], "verification": "verified", "verified_against": "Bounded synthesis of examined sources; score is adjudication.", "verified_on": "2026-10-09", "note": "" } ], "citation_ledger": [ { "n": 1, "citation": "Henninger JE, Oksuz O, Shrinivas K et al. RNA-Mediated Feedback Control of Transcriptional Condensates. Cell. 2021.", "tier": "A", "kind": "primary", "pmid": "33333019", "doi": "10.1016/j.cell.2020.11.030", "url": "https://pubmed.ncbi.nlm.nih.gov/33333019/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID33333019", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C1", "CSC1", "CSC2", "CSC3" ] }, { "n": 2, "citation": "Basu S, Mackowiak SD, Niskanen H et al. Unblending of Transcriptional Condensates in Human Repeat Expansion Disease. Cell. 2020.", "tier": "A", "kind": "primary", "pmid": "32386547", "doi": "10.1016/j.cell.2020.04.018", "url": "https://pubmed.ncbi.nlm.nih.gov/32386547/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID32386547", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C2", "CSC1", "CSC2" ] }, { "n": 3, "citation": "Cho WK, Spille JH, Hecht M et al. Mediator and RNA polymerase II clusters associate in transcription-dependent condensates. Science (New York, N.Y.). 2018.", "tier": "A", "kind": "primary", "pmid": "29930094", "doi": "10.1126/science.aar4199", "url": "https://pubmed.ncbi.nlm.nih.gov/29930094/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID29930094", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C3", "CSC1", "CSC2" ] }, { "n": 4, "citation": "Lee JH, Wang R, Xiong F et al. Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation. Molecular cell. 2021.", "tier": "A", "kind": "primary", "pmid": "34375583", "doi": "10.1016/j.molcel.2021.07.024", "url": "https://pubmed.ncbi.nlm.nih.gov/34375583/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID34375583", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C4", "CSC1", "CSC2" ] }, { "n": 5, "citation": "Wu Z, Pope SD, Ahmed NS et al. Regulation of inflammatory responses by pH-dependent transcriptional condensates. Cell. 2025.", "tier": "A", "kind": "primary", "pmid": "40680734", "doi": "10.1016/j.cell.2025.06.033", "url": "https://pubmed.ncbi.nlm.nih.gov/40680734/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-09", "status_checked_on": "2026-10-09", "study_id": "PMID40680734", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph7, 1:Results:paragraph12, 1:Results:paragraph13, 1:Results:paragraph14, 1:Results:paragraph15. No complete-paper or supplement audit claimed.", "carries_claims": [ "C5", "CSC1", "CSC2" ] }, { "n": 6, "citation": "Du M, Stitzinger SH, Spille JH et al. Direct observation of a condensate effect on super-enhancer controlled gene bursting. 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No complete-paper or supplement audit claimed.", "carries_claims": [ "C64", "CSC1", "CSC2", "CSC3", "CH" ] } ], "independence_basis": { "required": false, "lines": [ { "label": "Native MYOCD concentration and matched-expression IDR swaps", "sources": [ 14 ], "excludes_error": "Preserved occupancy and nontranscriptional aromatic-IDR rescue narrow generic binding loss; CDT1 nonfunctional condensation exposes composition dependence." }, { "label": "NELF stress loss and constitutive heterologous rescue", "sources": [ 15 ], "excludes_error": "Preserved nuclear targeting, complex assembly and basal promoter binding narrow generic protein failure; stress occupancy and recruitment still covary." }, { "label": "Matched abundance phase switching and native-hub imaging", "sources": [ 7, 30, 48 ], "excludes_error": "Drug/HOTag controls test phase effects without abundance increase; native super-resolution has distinct localization/model errors." } ], "shared_failure_mode_checked": true, "note": "Physical reconstitution, native imaging, genetic rescue and engineered phase switching fail differently. Together they establish capacity and context-dependent multivalent function. They do not all assay endogenous liquid-state necessity, so their convergence is credited to assembly alternatives rather than automatically to the LLPS conjunction. EWS followups share A673 labels, and early PolII imaging shares a platform." }, "consensus_validation": { "completed": true, "status": "documented_historical_discovery_and_reconciliation", "provider": "Consensus", "provider_mode": "Historical browser/connector use as recorded in the source artifacts", "local_audit_date": "2026-10-09", "primary_comparison_count": null, "reported_usage": [ { "path": "D:\\HypothesisCritic\\deliverables\\hsef_v53_popularity_ranks_41_45_2026-10-08\\transcriptional-condensates\\consensus\\usage.json", "metrics": { "browser_pro_queries": 2, "deep_queries": 0, "api_calls": 0, "original_passage_comparisons": 2, "targeted_studies_requested": 8, "abstract_aspect_comparisons": 0 } } ], "grade_changed": false, "score_before": { "hsef_level": "Γ", "hsef_descriptor": "Mechanistically plausible, partial system support", "confidence": "Moderate", "confidence_rationale": "64 primary reports with 10 selected partial-body examinations; density, heterogeneous controls and methodological heterogeneity set the confidence, not correctness and not the reviewer's access depth. Re-tested against the High band text, which requires extensive independent replication across labs, models and assay modalities: the band holds at Moderate.", "rests_on_non_peer_reviewed_work": false, "rationale": "Weakest-link aggregation yields Γ. SC1 has clear physical capacity and native assemblies but incomplete phase diagnosis; SC2 has strong selected assembly/rescue evidence without cleanly isolating liquid state from affinity and composition; SC3 lacks representative native phase-specific primacy. Stronger levels for multivalency models are not transferred to the stricter LLPS conjunction." }, "score_after": { "hsef_level": "Γ", "hsef_descriptor": "Mechanistically plausible, partial system support", "confidence": "Moderate", "confidence_rationale": "64 primary reports with 10 selected partial-body examinations; density, heterogeneous controls and methodological heterogeneity set the confidence, not correctness and not the reviewer's access depth. Re-tested against the High band text, which requires extensive independent replication across labs, models and assay modalities: the band holds at Moderate.", "rests_on_non_peer_reviewed_work": false, "rationale": "Weakest-link aggregation yields Γ. SC1 has clear physical capacity and native assemblies but incomplete phase diagnosis; SC2 has strong selected assembly/rescue evidence without cleanly isolating liquid state from affinity and composition; SC3 lacks representative native phase-specific primacy. 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