{ "$schema_version": "5.3", "review_mode": "fresh", "claim_restatement": { "index_wording": "Chromatin Accessibility = Transcriptional Competence", "entry_form": "claim", "gradeable_restatement": "Chromatin accessibility determines transcriptional competence, such that accessible loci are those available for transcription.", "restatement_required": true, "split_into": [], "parent_claim": null, "scope_qualifiers": [ { "qualifier": "Species, genotype, developmental window, exposure, baseline disease and measurement fixed before outcomes", "determinable_before_outcome": true, "determined_from": "Enrollment and experimental design, before results; no responder-defined scope.", "action": "retained" } ] }, "hypothesis": { "name": "Chromatin Accessibility = Transcriptional Competence", "central_claim": "Chromatin accessibility determines transcriptional competence, such that accessible loci are those available for transcription.", "proposed_mechanism": "Chromatin accessibility determines transcriptional competence, such that accessible loci are those available for transcription.", "claimed_scope": "Endogenous chromatin loci across specified cell states and developmental/replication windows; measured bulk or single-fiber accessibility is separated from physical DNA access, factor activity and actual transcription", "claimed_level": [ "initiation", "maintenance", "progression" ], "is_conjunctive": true, "conjunctive_note": "Index primary-subclaim SC2 retained. Necessity of accessibility itself is separated from multifunctional remodeler or factor necessity." }, "rubric_routing": { "primary_rubric": "03-epigenetics-gene-regulation.md", "secondary_rubrics": [], "index_notes_applied": [ "Index primary-subclaim SC2 retained. Necessity of accessibility itself is separated from multifunctional remodeler or factor necessity." ], "rubric_fit_note": "03 directly applies. The accessible state is an assay-dependent regulatory feature, not identical to absence of every nucleosome or large-scale chromatin decondensation. Native-locus, degron, drug, calibrated accessibility and nascent-transcription evidence is retained; gene/protein necessity is not silently recast as state necessity. Competence is potential to respond, which must be tested with a controlled activating challenge; baseline RNA absence at an open site alone is not a competence failure. The SC3 catalytic-dead-HAT test concerns actual activation sufficiency, a separate registered subclaim." }, "subclaim_matrix": { "subclaims": [ { "id": "SC1", "statement": "Accessibility and transcription are correlated.", "subclaim_type": "existence", "scope": "Endogenous locus, cell state, temporal resolution and intervention specified before outcomes", "claimed_scope": "Endogenous locus, cell state, temporal resolution and intervention specified before outcomes", "governing_rubric": "03-epigenetics-gene-regulation.md", "key_evidence_anchor": "Original perturbation with functional transcription/architecture and specificity controls", "hsef_level": "Β", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Accessibility and transcriptional state correlate extensively across original atlases, cell types and time courses. This existence subclaim is associational, with measurement scale, cell mixtures, motif sequence and transcriptional feedback affecting the correlation. Predictive accuracy does not establish causal direction." }, { "id": "SC2", "statement": "An accessible state is necessary for transcriptional competence.", "subclaim_type": "necessity", "scope": "Endogenous locus, cell state, temporal resolution and intervention specified before outcomes", "claimed_scope": "Endogenous locus, cell state, temporal resolution and intervention specified before outcomes", "governing_rubric": "03-epigenetics-gene-regulation.md", "key_evidence_anchor": "Original perturbation with functional transcription/architecture and specificity controls", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Acute endogenous remodeler perturbations and functional nascent-RNA readouts supply important mechanistic support. Yet they also perturb ATPase activity, transcription-factor occupancy, coactivator recruitment and nucleosome states; they do not establish that the accessible state as measured is universally necessary for transcriptional competence independently of those functions. The registered SC2 remains Γ. This does not mean physical DNA access is irrelevant or that remodelers lack endogenous causal effects." }, { "id": "SC3", "statement": "Accessibility is sufficient to activate transcription.", "subclaim_type": "sufficiency", "scope": "Endogenous locus, cell state, temporal resolution and intervention specified before outcomes", "claimed_scope": "Endogenous locus, cell state, temporal resolution and intervention specified before outcomes", "governing_rubric": "03-epigenetics-gene-regulation.md", "key_evidence_anchor": "Original perturbation with functional transcription/architecture and specificity controls", "hsef_level": "Β", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Opening alone is insufficient in a directly informative native-locus test: catalytic-dead dCas9-HAT restores asb11 accessibility in NPS-null zebrafish without restoring acetylation or transcription, while active HAT restores both. Promoter ATAC recovery above control also need not increase transcription above control. Positive active-HAT or ectopic-TF activation tests change more than opening. The broad sufficiency subclaim begins with Γ partial support and is downgraded one rung to Β by the specific opening-without-output falsification; Β is not a declaration that all opening is nonfunctional." }, { "id": "SC4", "statement": "Accessibility is causally upstream of transcription.", "subclaim_type": "primacy", "scope": "Endogenous locus, cell state, temporal resolution and intervention specified before outcomes", "claimed_scope": "Endogenous locus, cell state, temporal resolution and intervention specified before outcomes", "governing_rubric": "03-epigenetics-gene-regulation.md", "key_evidence_anchor": "Original perturbation with functional transcription/architecture and specificity controls", "hsef_level": "Β", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Opening can precede transcription during zebrafish genome activation, but postreplication transcription restart, paused-polymerase/BAF cooperation and local ncRNA transcription can instead generate or stabilize accessibility. The registered general upstream direction therefore cannot be universal. Partial Γ directional support is downgraded one rung to Β for verified direction-reversal contexts, rather than describing them as merely missing evidence." } ], "aggregation_rule": "primary-subclaim", "aggregation_preregistered": true, "aggregation_rationale": "Index primary-subclaim SC2 retained. Necessity of accessibility itself is separated from multifunctional remodeler or factor necessity.", "primary_subclaim_id": "SC2", "aggregation_derivation": "Overall Γ follows the preregistered primary necessity SC2: strong endogenous remodeler/factor causality exists, but necessity of the measured accessible state itself remains incompletely isolated. SC1 correlation is Β. Broad sufficiency SC3 and universal upstream SC4 are each Β after one-rung falsification downgrades from partial Γ. The alternative aggregation rules would return Β weakest-link and Γ primary/scope-matched.", "aggregation_alternatives": { "weakest_link_would_return": "Β", "primary_subclaim_would_return": "Γ", "scope_matched_would_return": "Γ", "note": "Separate narrow successes do not replace the preregistered full-scope gate." }, "index_rule_deviation": "" }, "competing_models": { "models_evaluated": [ { "rank_in_tournament": 1, "model_id": "M3", "is_nominal": false, "name": "Polymerase-remodeler-factor cooperation", "core_claim": "Paused polymerase, ATP-dependent remodelers and sequence-specific factors jointly stabilize locus-specific accessible states and transcription.", "explains_what_nominal_does_not": "Paused polymerase, ATP-dependent remodelers and sequence-specific factors jointly stabilize locus-specific accessible states and transcription.", "strongest_supporting_evidence": [ "Stage-specific inhibitors with calibration, ATPase-blocked intermediate retention and EP400 compensation map causal cooperation within specified cultured-cell settings." ], "strongest_contradictory_evidence": [ "This is not every developmental state: most early zebrafish opening persists without polymerase transcription; global inhibitors and multiple protein functions require timing controls." ], "hsef_level_for_this_model": "Ε", "rationale": "Stage-specific inhibitors with calibration, ATPase-blocked intermediate retention and EP400 compensation map causal cooperation within specified cultured-cell settings. This is not every developmental state: most early zebrafish opening persists without polymerase transcription; global inhibitors and multiple protein functions require timing controls." }, { "rank_in_tournament": 2, "model_id": "M2", "is_nominal": false, "name": "Pioneer and coactivator specificity", "core_claim": "Sequence-specific factors and their recruited coactivators carry regulatory specificity and can create or exploit accessible states.", "explains_what_nominal_does_not": "Sequence-specific factors and their recruited coactivators carry regulatory specificity and can create or exploit accessible states.", "strongest_supporting_evidence": [ "NPS mutants with targeted active-HAT rescue, OCT4/BRG1 dependence, domain/motif contrasts and productive/unproductive pioneer sites establish restricted factor/cofactor causality." ], "strongest_contradictory_evidence": [ "Factor labels are not universal categories; some nonclassical factors pioneer, and opening can occur without transcription." ], "hsef_level_for_this_model": "Ε", "rationale": "NPS mutants with targeted active-HAT rescue, OCT4/BRG1 dependence, domain/motif contrasts and productive/unproductive pioneer sites establish restricted factor/cofactor causality. Factor labels are not universal categories; some nonclassical factors pioneer, and opening can occur without transcription." }, { "rank_in_tournament": 3, "model_id": "M4", "is_nominal": false, "name": "Permissive accessibility with activation inputs", "core_claim": "Accessibility permits selected regulatory interactions but additional activating inputs determine output.", "explains_what_nominal_does_not": "Accessibility permits selected regulatory interactions but additional activating inputs determine output.", "strongest_supporting_evidence": [ "Open-before-transcription priming and dead-HAT opening without activation favor permissiveness rather than a sufficient switch." ], "strongest_contradictory_evidence": [ "The necessity of accessibility as an independently measured state has not been cleanly established across the registered scope." ], "hsef_level_for_this_model": "Γ", "rationale": "Open-before-transcription priming and dead-HAT opening without activation favor permissiveness rather than a sufficient switch. The necessity of accessibility as an independently measured state has not been cleanly established across the registered scope." }, { "rank_in_tournament": 4, "model_id": "M5", "is_nominal": false, "name": "Transcription-produced accessibility in defined contexts", "core_claim": "Initiation, pausing or upstream transcription builds or maintains open chromatin in specified windows.", "explains_what_nominal_does_not": "Initiation, pausing or upstream transcription builds or maintains open chromatin in specified windows.", "strongest_supporting_evidence": [ "Postreplication restart, local ncRNA terminator tests and polymerase/BAF synergy support restricted reverse-direction mechanisms." ], "strongest_contradictory_evidence": [ "This cannot replace all accessibility biology because polymerase-independent developmental opening is verified." ], "hsef_level_for_this_model": "Ε", "rationale": "Postreplication restart, local ncRNA terminator tests and polymerase/BAF synergy support restricted reverse-direction mechanisms. This cannot replace all accessibility biology because polymerase-independent developmental opening is verified." }, { "rank_in_tournament": 5, "model_id": "M1", "is_nominal": true, "name": "Accessibility directly determines competence", "core_claim": "Measured open chromatin universally defines loci available for transcription and directs activation upstream.", "explains_what_nominal_does_not": "Measured open chromatin universally defines loci available for transcription and directs activation upstream.", "strongest_supporting_evidence": [ "Robust correlations, acute BAF dependence and temporal priming provide partial support." ], "strongest_contradictory_evidence": [ "Multifunctional mediator perturbations, opening-only failure and reverse-direction contexts prevent the registered causal generalization." ], "hsef_level_for_this_model": "Γ", "rationale": "Robust correlations, acute BAF dependence and temporal priming provide partial support. Multifunctional mediator perturbations, opening-only failure and reverse-direction contexts prevent the registered causal generalization." } ], "tournament_summary": "Descriptive comparison; does not modify the nominal score. At the endogenous asb11 locus in NPS-null embryos, catalytic-dead HAT restores accessibility but not transcription, whereas active HAT restores both (PMID35182480). Together with paused-polymerase stabilization of BAF and ATPase-dependent eviction (PMID38049663), this separates a sufficient-accessibility switch from specific cooperative activation. It does not prove that every locus uses the same cooperation or that accessibility is dispensable.", "study_separating_rank1_from_rank2": "At the endogenous asb11 locus in NPS-null embryos, catalytic-dead HAT restores accessibility but not transcription, whereas active HAT restores both (PMID35182480). Together with paused-polymerase stabilization of BAF and ATPase-dependent eviction (PMID38049663), this separates a sufficient-accessibility switch from specific cooperative activation. It does not prove that every locus uses the same cooperation or that accessibility is dispensable.", "nominal_wins_only_by_funding_artifact": false, "level_unchanged_by_tournament": true }, "evidence_inventory": [ { "n": 1, "pmid": "38811575", "title": "Acute depletion of BRG1 reveals its primary function as an activator of transcription.", "citation": "Ren G, Ku WL, Ge G et al. Acute depletion of BRG1 reveals its primary function as an activator of transcription. Nature communications. 2024.", "doi": "10.1038/s41467-024-48911-z", "pmcid": "PMC11137027", "url": "https://pubmed.ncbi.nlm.nih.gov/38811575/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38811575/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID38811575", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Results:paragraph0, 1:Results:paragraph2, 1:Results:paragraph7, 1:Results:paragraph14. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "ex vivo", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Endogenous BRG1-AID depletion reduces nascent RNA, RNAPII occupancy and DHS accessibility in primary mouse cells without measured viability/growth defects.", "what_it_does_not_show": "BRG1 loss also changes nucleosomes, p300 and acetylation; it does not selectively remove accessible state while preserving other mediator functions.", "confounders_present": [ "BRG1 loss also changes nucleosomes, p300 and acetylation; it does not selectively remove accessible state while preserving other mediator 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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 2, "pmid": "34731603", "title": "Acute depletion of the ARID1A subunit of SWI/SNF complexes reveals distinct pathways for activation and repression of transcription.", "citation": "Blümli S, Wiechens N, Wu MY et al. Acute depletion of the ARID1A subunit of SWI/SNF complexes reveals distinct pathways for activation and repression of transcription. Cell reports. 2021.", "doi": "10.1016/j.celrep.2021.109943", "pmcid": "PMC8578704", "url": "https://pubmed.ncbi.nlm.nih.gov/34731603/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34731603/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID34731603", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Acute ARID1A degron causes rapid accessibility/EP300 changes but comparatively few early differentially expressed genes; later adaptive transcript changes dominate.", "what_it_does_not_show": "EP300 redistribution and multifactor effects prevent accessibility-specific necessity; steady-state RNA and timing affect apparent coupling.", "confounders_present": [ "EP300 redistribution and multifactor effects prevent accessibility-specific necessity; steady-state RNA and timing affect apparent coupling." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 3, "pmid": "33558760", "title": "Acute BAF perturbation causes immediate changes in chromatin accessibility.", "citation": "Schick S, Grosche S, Kohl KE et al. Acute BAF perturbation causes immediate changes in chromatin accessibility. Nature genetics. 2021.", "doi": "10.1038/s41588-021-00777-3", "pmcid": "PMC7614082", "url": "https://pubmed.ncbi.nlm.nih.gov/33558760/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33558760/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID33558760", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 0:Results:paragraph0, 0:Results:paragraph1, 0:Results:paragraph5, 0:Results:paragraph6. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "in vivo cellular", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "dTAG, ATPase inhibition and degradation rapidly alter BAF-dependent accessibility with smaller early PRO-seq changes under nontoxic inhibitor conditions.", "what_it_does_not_show": "dTAG clone begins with about50%SMARCA4 and baseline changes; rapid accessibility loss is not a selectively isolated state perturbation or immediate global loss of transcription.", "confounders_present": [ "dTAG clone begins with about50%SMARCA4 and baseline changes; rapid accessibility loss is not a selectively isolated state perturbation or immediate global loss of 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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 4, "pmid": "38049663", "title": "The BAF chromatin remodeler synergizes with RNA polymerase II and transcription factors to evict nucleosomes.", "citation": "Brahma S, Henikoff S. The BAF chromatin remodeler synergizes with RNA polymerase II and transcription factors to evict nucleosomes. Nature genetics. 2024.", "doi": "10.1038/s41588-023-01603-8", "pmcid": "PMC10786724", "url": "https://pubmed.ncbi.nlm.nih.gov/38049663/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38049663/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID36711459" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "BAF_RNAPII_COOPERATION_PUBLISHED", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Results:paragraph2, 1:Results:paragraph3, 1:Results:paragraph9, 1:Results:paragraph14. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "in vivo cellular", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Chemical-genetic time courses show paused RNAPII stabilizes BAF occupancy and ATPase-dependent eviction; TF binding confers locus specificity.", "what_it_does_not_show": "Inhibition changes transcription machinery directly;≤2htriptolide viability controls do not extend to4h, and bidirectional synergy is not universal upstream opening.", "confounders_present": [ "Inhibition changes transcription machinery directly;≤2htriptolide viability controls do not extend to4h, and bidirectional synergy is not universal upstream opening." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [ "Polymerase/BAF culture and antibody/chemical profiling framework; multiple inhibitors must be judged for distinct off-target errors." ] }, { "n": 5, "pmid": "37922899", "title": "Global identification of SWI/SNF targets reveals compensation by EP400.", "citation": "Martin BJE, Ablondi EF, Goglia C et al. Global identification of SWI/SNF targets reveals compensation by EP400. Cell. 2023.", "doi": "10.1016/j.cell.2023.10.006", "pmcid": "PMC11307202", "url": "https://pubmed.ncbi.nlm.nih.gov/37922899/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37922899/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID37922899", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:RESULTS:paragraph1, 1:RESULTS:paragraph2, 1:RESULTS:paragraph6, 1:RESULTS:paragraph8, 1:RESULTS:paragraph25, 1:RESULTS:paragraph26. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "in vivo cellular", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Fast SWISNF inhibition reduces accessibility/transcription; EP400 restores promoter accessibility and expression during prolonged inhibition, with no toxicity in early windows.", "what_it_does_not_show": "Above-control ATAC recovery need not increase transcription above control; factor activity and state remain coupled despite orthogonal inhibitor/degrader/EP400 tests.", "confounders_present": [ "Above-control ATAC recovery need not increase transcription above control; factor activity and state remain coupled despite orthogonal inhibitor/degrader/EP400 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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [ "ATPase inhibitor BRM014 also used in other BAF reports; orthogonal degrader and EP400 interventions add controls but not accessibility-only isolation." ] }, { "n": 6, "pmid": "40846763", "title": "Precise modulation of BRG1 levels reveals features of mSWI/SNF dosage sensitivity.", "citation": "Hagihara Y, Zhang C, Zhang Y. Precise modulation of BRG1 levels reveals features of mSWI/SNF dosage sensitivity. Nature genetics. 2025.", "doi": "10.1038/s41588-025-02305-z", "pmcid": "PMC12425804", "url": "https://pubmed.ncbi.nlm.nih.gov/40846763/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40846763/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID40846763", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Dose-graded BRG1 degradation reveals enhancer-specific accessibility and buffered transcription with promoters/insulators often unaffected.", "what_it_does_not_show": "Protein dosage tests multifunctional remodeler, not accessible state alone; nonlinear buffering defeats one-to-one competence inference.", "confounders_present": [ "Protein dosage tests multifunctional remodeler, not accessible state alone; nonlinear buffering defeats one-to-one competence 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 7, "pmid": "33765415", "title": "Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release.", "citation": "Narita T, Ito S, Higashijima Y et al. Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release. Molecular cell. 2021.", "doi": "10.1016/j.molcel.2021.03.008", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33765415/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33765415/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID33765415", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "in vivo cellular", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "p300/CBP catalytic activity controls rapid PIC/RNAPII recruitment and pause release while TF/coactivator recruitment persists.", "what_it_does_not_show": "This isolates acetylation-dependent activation, not accessibility-only necessity; original body was not publicly retrieved in this audit.", "confounders_present": [ "This isolates acetylation-dependent activation, not accessibility-only necessity; original body was not publicly retrieved in this audit." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 8, "pmid": "28287392", "title": "The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells.", "citation": "King HW, Klose RJ. The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells. eLife. 2017.", "doi": "10.7554/eLife.22631", "pmcid": "PMC5400504", "url": "https://pubmed.ncbi.nlm.nih.gov/28287392/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28287392/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID28287392", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "OCT4 loss and BRG1 requirement constrain endogenous mouseESC binding, accessibility and pluripotency transcription.", "what_it_does_not_show": "Factor/remodeler functions and cell-state regulation are not independent accessible-state manipulation.", "confounders_present": [ "Factor/remodeler functions and cell-state regulation are not independent accessible-state manipulation." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 9, "pmid": "31940339", "title": "Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation.", "citation": "Pálfy M, Schulze G, Valen E et al. Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation. PLoS genetics. 2020.", "doi": "10.1371/journal.pgen.1008546", "pmcid": "PMC6986763", "url": "https://pubmed.ncbi.nlm.nih.gov/31940339/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31940339/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "ZEBRAFISH_NPS_PRIMING_2020", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Results:paragraph2, 1:Results:paragraph4, 1:Results:paragraph7, 1:Results:paragraph12. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Zebrafish regulatory opening precedes transcription and persists under alpha-amanitin except miR430; maternal-factor loss reduces opening.", "what_it_does_not_show": "Priming is not sufficient activation; transcription independence in this window is not universal across replication/cell states, and nearest-neighbor enhancer links are inferred.", "confounders_present": [ "Priming is not sufficient activation; transcription independence in this window is not universal across replication/cell states, and nearest-neighbor enhancer links are inferred." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [ "Zebrafish maternal-factor/ZGA framework shared with later NPS work; does not automatically establish an independent causal error class." ] }, { "n": 10, "pmid": "35182480", "title": "The landscape of pioneer factor activity reveals the mechanisms of chromatin reprogramming and genome activation.", "citation": "Miao L, Tang Y, Bonneau AR et al. The landscape of pioneer factor activity reveals the mechanisms of chromatin reprogramming and genome activation. Molecular cell. 2022.", "doi": "10.1016/j.molcel.2022.01.024", "pmcid": "PMC9327391", "url": "https://pubmed.ncbi.nlm.nih.gov/35182480/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35182480/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "ZEBRAFISH_NPS_TARGETED_RESCUE_2022", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Results:paragraph1, 1:Results:paragraph7, 1:Results:paragraph8. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": true, "endogenous": true, "direction": "contradicts", "what_it_shows": "NPS-null zebrafish have lost enhancer opening; locus dCas9 active HAT restores transcription, while catalytic-dead HAT restores opening without transcription at asb11.", "what_it_does_not_show": "Clean opening-without-activation discriminates sufficiency but does not prove a universal necessity of measured ATAC; targetedHAT also changes acetylation/cofactor recruitment.", "confounders_present": [ "Clean opening-without-activation discriminates sufficiency but does not prove a universal necessity of measured ATAC; targetedHAT also changes acetylation/cofactor recruitment." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [ "Zebrafish NPS/ZGA system; targeted HAT rescue provides a distinct mechanistic contrast rather than an independent population." ] }, { "n": 11, "pmid": "31126739", "title": "Transcription Restart Establishes Chromatin Accessibility after DNA Replication.", "citation": "Stewart-Morgan KR, Reverón-Gómez N, Groth A. Transcription Restart Establishes Chromatin Accessibility after DNA Replication. Molecular cell. 2019.", "doi": "10.1016/j.molcel.2019.04.033", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31126739/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31126739/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID31348880" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID31126739", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "in vivo cellular", "decisive_perturbation": true, "endogenous": true, "direction": "contradicts", "what_it_shows": "Postreplication transcription restart is required to restore active chromatin accessibility in mouseESCs by repli-ATAC and transcription inhibition.", "what_it_does_not_show": "Replication-conditioned restoration is not every locus/state; linked erratum PMID31348880 was identified but its details were not read.", "confounders_present": [ "Replication-conditioned restoration is not every locus/state; linked erratum PMID31348880 was identified but its details were not read." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 12, "pmid": "39191261", "title": "RNA polymerases reshape chromatin architecture and couple transcription on individual fibers.", "citation": "Tullius TW, Isaac RS, Dubocanin D et al. RNA polymerases reshape chromatin architecture and couple transcription on individual fibers. Molecular cell. 2024.", "doi": "10.1016/j.molcel.2024.08.013", "pmcid": "PMC11500009", "url": "https://pubmed.ncbi.nlm.nih.gov/39191261/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39191261/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID38187631" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "DROSOPHILA_FIBERSEQ_PUBLISHED", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Fiber-seq resolves polymerase/nucleosome footprints and pausing-dependent nucleosome destabilization/coupling on individual Drosophila fibers.", "what_it_does_not_show": "Single-fiber structure and perturbation address transcription-to-chromatin feedback, not opening as an independent universal competence determinant.", "confounders_present": [ "Single-fiber structure and perturbation address transcription-to-chromatin feedback, not opening as an independent universal competence determinant." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 13, "pmid": "36130732", "title": "OCT4 interprets and enhances nucleosome flexibility.", "citation": "MacCarthy CM, Huertas J, Ortmeier C et al. OCT4 interprets and enhances nucleosome flexibility. Nucleic acids research. 2022.", "doi": "10.1093/nar/gkac755", "pmcid": "PMC9561370", "url": "https://pubmed.ncbi.nlm.nih.gov/36130732/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36130732/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID36130732", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vitro", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Experiments/simulations show OCT4 stabilizes flexible/open nucleosome conformations depending on motif position and histone tails.", "what_it_does_not_show": "Structural binding does not establish endogenous transcript necessity or sufficiency.", "confounders_present": [ "Structural binding does not establish endogenous transcript necessity or sufficiency." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 14, "pmid": "32027821", "title": "Nucleosomal DNA Dynamics Mediate Oct4 Pioneer Factor Binding.", "citation": "Huertas J, MacCarthy CM, Schöler HR et al. Nucleosomal DNA Dynamics Mediate Oct4 Pioneer Factor Binding. Biophysical journal. 2020.", "doi": "10.1016/j.bpj.2019.12.038", "pmcid": "PMC7202942", "url": "https://pubmed.ncbi.nlm.nih.gov/32027821/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32027821/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID32027821", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Weak", "system": "in silico", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Molecular simulations predict nucleosome breathing/twisting and partial-motif recognition permit OCT4 binding.", "what_it_does_not_show": "Computation is original research but no functional causal transcription crossing or direct endogenous measurement.", "confounders_present": [ "Computation is original research but no functional causal transcription crossing or direct endogenous measurement." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 15, "pmid": "29126175", "title": "Conventional and pioneer modes of glucocorticoid receptor interaction with enhancer chromatin in vivo.", "citation": "Johnson TA, Chereji RV, Stavreva DA et al. Conventional and pioneer modes of glucocorticoid receptor interaction with enhancer chromatin in vivo. Nucleic acids research. 2018.", "doi": "10.1093/nar/gkx1044", "pmcid": "PMC5758879", "url": "https://pubmed.ncbi.nlm.nih.gov/29126175/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29126175/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID29126175", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Hormone-induced GR binds both preaccessible and nucleosomal/inaccessible enhancer classes and recruits BRG1 with shifts.", "what_it_does_not_show": "GR/BRG1 perturbation and hormone exposure do not isolate accessibility state; nucleosomal and DNase sensitivity are not interchangeable.", "confounders_present": [ "GR/BRG1 perturbation and hormone exposure do not isolate accessibility state; nucleosomal and DNase sensitivity are not interchangeable." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 16, "pmid": "35672415", "title": "Dynamic nucleosome landscape elicits a noncanonical GATA2 pioneer model.", "citation": "Li T, Liu Q, Chen Z et al. Dynamic nucleosome landscape elicits a noncanonical GATA2 pioneer model. Nature communications. 2022.", "doi": "10.1038/s41467-022-30960-x", "pmcid": "PMC9174260", "url": "https://pubmed.ncbi.nlm.nih.gov/35672415/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35672415/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID35672415", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Androgen time courses support GATA2 binding at inaccessible nucleosome edges before remodeling and downstream regulation.", "what_it_does_not_show": "Multifactor binding/state changes do not establish opening-only competence or generalize from LNCaPcells.", "confounders_present": [ "Multifactor binding/state changes do not establish opening-only competence or generalize from LNCaPcells." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 17, "pmid": "26922637", "title": "GATA3-dependent cellular reprogramming requires activation-domain dependent recruitment of a chromatin remodeler.", "citation": "Takaku M, Grimm SA, Shimbo T et al. GATA3-dependent cellular reprogramming requires activation-domain dependent recruitment of a chromatin remodeler. Genome biology. 2016.", "doi": "10.1186/s13059-016-0897-0", "pmcid": "PMC4769547", "url": "https://pubmed.ncbi.nlm.nih.gov/26922637/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26922637/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID26922637", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "GATA3 activation-domain deletion retains binding but prevents productive remodeling/MET; some bound loci slide nucleosomes without becoming accessible.", "what_it_does_not_show": "Ectopic reprogramming and lost recruitment functions do not establish endogenous accessible-state necessity.", "confounders_present": [ "Ectopic reprogramming and lost recruitment functions do not establish endogenous accessible-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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 18, "pmid": "31253573", "title": "Pioneer Factor-Nucleosome Binding Events during Differentiation Are Motif Encoded.", "citation": "Meers MP, Janssens DH, Henikoff S. Pioneer Factor-Nucleosome Binding Events during Differentiation Are Motif Encoded. Molecular cell. 2019.", "doi": "10.1016/j.molcel.2019.05.025", "pmcid": "PMC6697550", "url": "https://pubmed.ncbi.nlm.nih.gov/31253573/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31253573/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID31253573", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human cellular", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "HumanESC differentiation profiles show motif/context-dependent TF nucleosome binding, including at accessible loci.", "what_it_does_not_show": "Computational occupancy classification and time course do not selectively test necessity or sufficiency.", "confounders_present": [ "Computational occupancy classification and time course do not selectively test necessity or sufficiency." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 19, "pmid": "28212747", "title": "Catalytic-Independent Functions of PARP-1 Determine Sox2 Pioneer Activity at Intractable Genomic Loci.", "citation": "Liu Z, Kraus WL. Catalytic-Independent Functions of PARP-1 Determine Sox2 Pioneer Activity at Intractable Genomic Loci. Molecular cell. 2017.", "doi": "10.1016/j.molcel.2017.01.017", "pmcid": "PMC5319724", "url": "https://pubmed.ncbi.nlm.nih.gov/28212747/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28212747/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID28212747", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "PARP1 cooperates with Sox2 nucleosome binding independently of catalytic activity at selected nativeESC loci.", "what_it_does_not_show": "Specific protein cooperation supports pioneer access but does not isolate opening from Sox2/cofactor regulation.", "confounders_present": [ "Specific protein cooperation supports pioneer access but does not isolate opening from Sox2/cofactor regulation." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 20, "pmid": "34984978", "title": "A test of the pioneer factor hypothesis using ectopic liver gene activation.", "citation": "Hansen JL, Loell KJ, Cohen BA. A test of the pioneer factor hypothesis using ectopic liver gene activation. eLife. 2022.", "doi": "10.7554/eLife.73358", "pmcid": "PMC8849321", "url": "https://pubmed.ncbi.nlm.nih.gov/34984978/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34984978/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID34984978", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Esrrb Unlocks Silenced Enhancers for Reprogramming to Naive Pluripotency. Cell stem cell. 2018.", "doi": "10.1016/j.stem.2018.05.020", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/29910149/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29910149/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID30526884" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID29910149", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Promoter G-quadruplex folding precedes transcription and is controlled by chromatin. Genome biology. 2021.", "doi": "10.1186/s13059-021-02346-7", "pmcid": "PMC8103603", "url": "https://pubmed.ncbi.nlm.nih.gov/33962653/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33962653/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID33962653", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Genome-wide analyses of chromatin interactions after the loss of Pol I, Pol II, and Pol III. Genome biology. 2020.", "doi": "10.1186/s13059-020-02067-3", "pmcid": "PMC7331254", "url": "https://pubmed.ncbi.nlm.nih.gov/32616013/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32616013/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID32616013", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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The Transcriptionally Permissive Chromatin State of Embryonic Stem Cells Is Acutely Tuned to Translational Output. Cell stem cell. 2018.", "doi": "10.1016/j.stem.2018.02.004", "pmcid": "PMC5836508", "url": "https://pubmed.ncbi.nlm.nih.gov/29499153/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29499153/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID29499153", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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The chromatin accessibility landscape of primary human cancers. Science (New York, N.Y.). 2018.", "doi": "10.1126/science.aav1898", "pmcid": "PMC6408149", "url": "https://pubmed.ncbi.nlm.nih.gov/30361341/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30361341/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID30361341", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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A Single-Cell Atlas of In Vivo Mammalian Chromatin Accessibility. Cell. 2018.", "doi": "10.1016/j.cell.2018.06.052", "pmcid": "PMC6158300", "url": "https://pubmed.ncbi.nlm.nih.gov/30078704/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30078704/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID30078704", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Single-cell chromatin accessibility reveals principles of regulatory variation. Nature. 2015.", "doi": "10.1038/nature14590", "pmcid": "PMC4685948", "url": "https://pubmed.ncbi.nlm.nih.gov/26083756/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26083756/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID26083756", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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A human cell atlas of fetal chromatin accessibility. Science (New York, N.Y.). 2020.", "doi": "10.1126/science.aba7612", "pmcid": "PMC7785298", "url": "https://pubmed.ncbi.nlm.nih.gov/33184180/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33184180/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID33184180", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Pooled CRISPR screens with joint single-nucleus chromatin accessibility and transcriptome profiling. Nature biotechnology. 2025.", "doi": "10.1038/s41587-024-02475-x", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/39572737/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39572737/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID39572737", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Single-nucleus RNA and ATAC sequencing reveals the impact of chromatin accessibility on gene expression in Arabidopsis roots at the single-cell level. Molecular plant. 2021.", "doi": "10.1016/j.molp.2021.01.001", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33422696/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33422696/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID33422696", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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METTL3 uncouples chromatin accessibility from transcription during retinal development. Stem cell reports. 2025.", "doi": "10.1016/j.stemcr.2025.102690", "pmcid": "PMC12790738", "url": "https://pubmed.ncbi.nlm.nih.gov/41135527/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41135527/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID41256642" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID41135527", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": true, "direction": "contradicts", "what_it_shows": "METTL3 loss/degron and RNA editing reveal retinal transcription regulation with direct chromatin targets showing weak accessibility-output correlation.", "what_it_does_not_show": "RNA stability/m6A are alternative mediators; uncoupling does not prove no locus ever depends on accessibility.", "confounders_present": [ "RNA stability/m6A are alternative mediators; uncoupling does not prove no locus ever depends on accessibility." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 37, "pmid": "33033242", "title": "Genome-wide chromatin accessibility is restricted by ANP32E.", "citation": "Murphy KE, Meng FW, Makowski CE et al. Genome-wide chromatin accessibility is restricted by ANP32E. Nature communications. 2020.", "doi": "10.1038/s41467-020-18821-x", "pmcid": "PMC7546623", "url": "https://pubmed.ncbi.nlm.nih.gov/33033242/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33033242/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID33033242", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "ANP32E loss changesH2AZpositioning, accessibility, TFbinding and neighboring expression in fibroblasts.", "what_it_does_not_show": "Histone-variant/remodeler functions and broad perturbation do not isolate accessible state from other regulatory inputs.", "confounders_present": [ "Histone-variant/remodeler functions and broad perturbation do not isolate accessible state from other regulatory inputs." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 38, "pmid": "33927415", "title": "Profiling the genetic determinants of chromatin accessibility with scalable single-cell CRISPR screens.", "citation": "Liscovitch-Brauer N, Montalbano A, Deng J et al. Profiling the genetic determinants of chromatin accessibility with scalable single-cell CRISPR screens. Nature biotechnology. 2021.", "doi": "10.1038/s41587-021-00902-x", "pmcid": "PMC8516442", "url": "https://pubmed.ncbi.nlm.nih.gov/33927415/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33927415/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID33927415", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "CRISPR-sciATAC perturbations map remodeler-specific accessibility, withEZH2loss/HOXexpression examples.", "what_it_does_not_show": "Chronic gene knockouts and state changes are not accessibility-only endogenous necessity tests.", "confounders_present": [ "Chronic gene knockouts and state changes are not accessibility-only endogenous necessity 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 39, "pmid": "34038741", "title": "Genetic effects on liver chromatin accessibility identify disease regulatory variants.", "citation": "Currin KW, Erdos MR, Narisu N et al. Genetic effects on liver chromatin accessibility identify disease regulatory variants. American journal of human genetics. 2021.", "doi": "10.1016/j.ajhg.2021.05.001", "pmcid": "PMC8323023", "url": "https://pubmed.ncbi.nlm.nih.gov/34038741/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34038741/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID34038741", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Human livercaQTLs identify allele-associated accessibility and aLITAFvariant has allele-specific binding/transcription activity.", "what_it_does_not_show": "Small tissue cohort, inferredgene links and alteredTFsequence confound accessibility mediation; not a pure state instrument.", "confounders_present": [ "Small tissue cohort, inferredgene links and alteredTFsequence confound accessibility mediation; not a pure state instrument." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 40, "pmid": "32427842", "title": "HOX13-dependent chromatin accessibility underlies the transition towards the digit development program.", "citation": "Desanlis I, Kherdjemil Y, Mayran A et al. HOX13-dependent chromatin accessibility underlies the transition towards the digit development program. Nature communications. 2020.", "doi": "10.1038/s41467-020-16317-2", "pmcid": "PMC7237422", "url": "https://pubmed.ncbi.nlm.nih.gov/32427842/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32427842/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID32427842", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "HOX13 function is required for distal-limb accessibility and permitsHOXA11target binding in engineered limbs.", "what_it_does_not_show": "DevelopmentalTFloss/ectopicHOXA11has multiple regulatory effects; independent accessibility-state necessity remains untested.", "confounders_present": [ "DevelopmentalTFloss/ectopicHOXA11has multiple regulatory effects; independent accessibility-state necessity remains untested." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 41, "pmid": "37488435", "title": "The pioneer factor SOX9 competes for epigenetic factors to switch stem cell fates.", "citation": "Yang Y, Gomez N, Infarinato N et al. The pioneer factor SOX9 competes for epigenetic factors to switch stem cell fates. Nature cell biology. 2023.", "doi": "10.1038/s41556-023-01184-y", "pmcid": "PMC10415178", "url": "https://pubmed.ncbi.nlm.nih.gov/37488435/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37488435/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID37488435", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Engineered SOX9 reactivation opens hair-follicle enhancers and redistributes cofactors away from epidermal programs, inducing fate switching.", "what_it_does_not_show": "Sustained ectopic TF and cofactor competition do not prove accessibility-only activation or normal endogenous scope.", "confounders_present": [ "Sustained ectopic TF and cofactor competition do not prove accessibility-only activation or normal endogenous scope." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 42, "pmid": "35550615", "title": "ETV2 functions as a pioneer factor to regulate and reprogram the endothelial lineage.", "citation": "Gong W, Das S, Sierra-Pagan JE et al. ETV2 functions as a pioneer factor to regulate and reprogram the endothelial lineage. Nature cell biology. 2022.", "doi": "10.1038/s41556-022-00901-3", "pmcid": "PMC11827897", "url": "https://pubmed.ncbi.nlm.nih.gov/35550615/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35550615/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID35550615", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "ETV2 binds nucleosomal DNA and recruits BRG1 during engineered endothelial differentiation/reprogramming.", "what_it_does_not_show": "TF/remodeler/acetylation coupled functions and engineered state restrict necessity and generalization.", "confounders_present": [ "TF/remodeler/acetylation coupled functions and engineered state restrict necessity and generalization." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 43, "pmid": "34197620", "title": "Pax7 pioneer factor action requires both paired and homeo DNA binding domains.", "citation": "Pelletier A, Mayran A, Gouhier A et al. Pax7 pioneer factor action requires both paired and homeo DNA binding domains. Nucleic acids research. 2021.", "doi": "10.1093/nar/gkab561", "pmcid": "PMC8287922", "url": "https://pubmed.ncbi.nlm.nih.gov/34197620/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34197620/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID34197620", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Pax7 DNA-binding domain/motif mutants separate high-affinity pioneering from low-affinity heterochromatin binding.", "what_it_does_not_show": "DNA-binding/domain changes do not selectively remove accessibility while preserving activator functions.", "confounders_present": [ "DNA-binding/domain changes do not selectively remove accessibility while preserving activator 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 44, "pmid": "37563108", "title": "Stepwise modifications of transcriptional hubs link pioneer factor activity to a burst of transcription.", "citation": "Cho CY, O'Farrell PH. Stepwise modifications of transcriptional hubs link pioneer factor activity to a burst of transcription. Nature communications. 2023.", "doi": "10.1038/s41467-023-40485-6", "pmcid": "PMC10415302", "url": "https://pubmed.ncbi.nlm.nih.gov/37563108/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37563108/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID37563108", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Endogenous tagging/live imaging shows Zelda/coactivator/RNAPII cluster cascade before transcription and dispersal during elongation.", "what_it_does_not_show": "Cluster timing is not direct accessible-state necessity; imaging alone does not prove condensate mechanism.", "confounders_present": [ "Cluster timing is not direct accessible-state necessity; imaging alone does not prove condensate 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 45, "pmid": "19349581", "title": "Large-scale chromatin structure of inducible genes: transcription on a condensed, linear template.", "citation": "Hu Y, Kireev I, Plutz M et al. Large-scale chromatin structure of inducible genes: transcription on a condensed, linear template. The Journal of cell biology. 2009.", "doi": "10.1083/jcb.200809196", "pmcid": "PMC2700507", "url": "https://pubmed.ncbi.nlm.nih.gov/19349581/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/19349581/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID19349581", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "Near-endogenous-level transcription occurs on condensed multimegabase BAC transgene fibers with modest induced extension.", "what_it_does_not_show": "BAC arrays and large-scale compaction are not endogenous local ATAC state; evidence cannot disprove all microscopic access requirements.", "confounders_present": [ "BAC arrays and large-scale compaction are not endogenous local ATAC state; evidence cannot disprove all microscopic access requirements." ], "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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 46, "pmid": "27548707", "title": "Transcription upregulation via force-induced direct stretching of chromatin.", "citation": "Tajik A, Zhang Y, Wei F et al. Transcription upregulation via force-induced direct stretching of chromatin. Nature materials. 2016.", "doi": "10.1038/nmat4729", "pmcid": "PMC5121013", "url": "https://pubmed.ncbi.nlm.nih.gov/27548707/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27548707/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID27548707", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Mechanical strain upregulates DHFR BAC transgene transcription with direction/actomyosin controls.", "what_it_does_not_show": "Reporter and force-mediated nuclear inputs do not establish accessibility-only endogenous sufficiency.", "confounders_present": [ "Reporter and force-mediated nuclear inputs do not establish accessibility-only endogenous sufficiency." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 47, "pmid": "18820678", "title": "Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs.", "citation": "Hirota K, Miyoshi T, Kugou K et al. Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs. Nature. 2008.", "doi": "10.1038/nature07348", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/18820678/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/18820678/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID18820678", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Systematic Study of Nucleosome-Displacing Factors in Budding Yeast. Molecular cell. 2018.", "doi": "10.1016/j.molcel.2018.06.017", "pmcid": "PMC6086576", "url": "https://pubmed.ncbi.nlm.nih.gov/30017582/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30017582/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID30017582", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Collaboration between distinct SWI/SNF chromatin remodeling complexes directs enhancer selection and activation of macrophage inflammatory genes. Immunity. 2024.", "doi": "10.1016/j.immuni.2024.05.008", "pmcid": "PMC11324393", "url": "https://pubmed.ncbi.nlm.nih.gov/38843835/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38843835/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID38843835", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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The SWI/SNF PBAF complex facilitates REST occupancy at repressive chromatin. Molecular cell. 2025.", "doi": "10.1016/j.molcel.2025.03.026", "pmcid": "PMC12048221", "url": "https://pubmed.ncbi.nlm.nih.gov/40252649/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40252649/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID39229151" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID40252649", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Chromatin Fiber Invasion and Nucleosome Displacement by the Rap1 Transcription Factor. Molecular cell. 2020.", "doi": "10.1016/j.molcel.2019.10.025", "pmcid": "PMC7005674", "url": "https://pubmed.ncbi.nlm.nih.gov/31761495/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31761495/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID31761495", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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CLOCK:BMAL1 is a pioneer-like transcription factor. Genes & development. 2014.", "doi": "10.1101/gad.228536.113", "pmcid": "PMC3894415", "url": "https://pubmed.ncbi.nlm.nih.gov/24395244/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24395244/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID24395244", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "CLOCK/BMAL1 rhythmic binding/nucleosome changes recruit other factors with heterogeneous output.", "what_it_does_not_show": "Rhythmic coupling and TF intervention do not isolate accessibility from clock regulation.", "confounders_present": [ "Rhythmic coupling and TF intervention do not isolate accessibility from clock regulation." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 54, "pmid": "31964861", "title": "Mechanisms governing the pioneering and redistribution capabilities of the non-classical pioneer PU.1.", "citation": "Minderjahn J, Schmidt A, Fuchs A et al. Mechanisms governing the pioneering and redistribution capabilities of the non-classical pioneer PU.1. Nature communications. 2020.", "doi": "10.1038/s41467-019-13960-2", "pmcid": "PMC6972792", "url": "https://pubmed.ncbi.nlm.nih.gov/31964861/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31964861/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID32098963" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID31964861", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Chromatin accessibility promotes hematopoietic and leukemia stem cell activity. Nature communications. 2020.", "doi": "10.1038/s41467-020-15221-z", "pmcid": "PMC7076002", "url": "https://pubmed.ncbi.nlm.nih.gov/32179749/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32179749/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID32179749", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "HMGN1 overexpression increases accessibility/stem-cell activity and cooperates with an AML fusion; HAT inhibition relieves the differentiation block.", "what_it_does_not_show": "Overexpression, leukemia mutation and histone effects cannot prove a generic accessible-state driver.", "confounders_present": [ "Overexpression, leukemia mutation and histone effects cannot prove a generic accessible-state driver." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 56, "pmid": "38015476", "title": "Chromatin accessibility and pioneer factor FOXA1 restrict glucocorticoid receptor action in prostate cancer.", "citation": "Helminen L, Huttunen J, Tulonen M et al. Chromatin accessibility and pioneer factor FOXA1 restrict glucocorticoid receptor action in prostate cancer. Nucleic acids research. 2024.", "doi": "10.1093/nar/gkad1126", "pmcid": "PMC10810216", "url": "https://pubmed.ncbi.nlm.nih.gov/38015476/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38015476/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID38015476", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "GR uses mostly preaccessible FOXA1 sites in resistant prostate cells; FOXA1 silencing increases GR activity through NR3C1 de-repression.", "what_it_does_not_show": "Factor-abundance repression and p300 activity explain output; preaccess alone does not dictate receptor transcription.", "confounders_present": [ "Factor-abundance repression and p300 activity explain output; preaccess alone does not dictate receptor 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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 57, "pmid": "25849900", "title": "Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers.", "citation": "Hilton IB, D'Ippolito AM, Vockley CM et al. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nature biotechnology. 2015.", "doi": "10.1038/nbt.3199", "pmcid": "PMC4430400", "url": "https://pubmed.ncbi.nlm.nih.gov/25849900/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25849900/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID25849900", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Targeted dCas9-p300 core acetylation activates endogenous promoter/enhancer target genes with specificity.", "what_it_does_not_show": "Catalytic acetylation/coactivator recruitment is more than opening; artificial tethering is not accessibility-only sufficiency.", "confounders_present": [ "Catalytic acetylation/coactivator recruitment is more than opening; artificial tethering is not accessibility-only sufficiency." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 58, "pmid": "35271371", "title": "CRISPR-Mediated Synergistic Epigenetic and Transcriptional Control.", "citation": "Dominguez AA, Chavez MG, Urke A et al. CRISPR-Mediated Synergistic Epigenetic and Transcriptional Control. The CRISPR journal. 2022.", "doi": "10.1089/crispr.2021.0099", "pmcid": "PMC9206482", "url": "https://pubmed.ncbi.nlm.nih.gov/35271371/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35271371/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID35271371", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Combined VPR/p300 epigenetic/transcriptional effectors enhance endogenous gene activation with off-target characterization.", "what_it_does_not_show": "Composite engineered activators cannot isolate accessible-state sufficiency and retain off-target concerns.", "confounders_present": [ "Composite engineered activators cannot isolate accessible-state sufficiency and retain off-target concerns." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 59, "pmid": "38593804", "title": "Enhancer switching in cell lineage priming is linked to eRNA, Brg1's AT-hook, and SWI/SNF recruitment.", "citation": "Saha D, Animireddy S, Lee J et al. Enhancer switching in cell lineage priming is linked to eRNA, Brg1's AT-hook, and SWI/SNF recruitment. Molecular cell. 2024.", "doi": "10.1016/j.molcel.2024.03.013", "pmcid": "PMC11104297", "url": "https://pubmed.ncbi.nlm.nih.gov/38593804/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38593804/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID38593804", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "BRG1 AT-hook/eRNA association and perturbations link stage-specific SWI/SNF recruitment with enhancer/coactivator activation.", "what_it_does_not_show": "RNA binding/transcriptional inputs and factor functions remain coupled; this is not universal upstream opening or generic competence.", "confounders_present": [ "RNA binding/transcriptional inputs and factor functions remain coupled; this is not universal upstream opening or generic competence." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 60, "pmid": "35858748", "title": "ATAC-STARR-seq reveals transcription factor-bound activators and silencers within chromatin-accessible regions of the human genome.", "citation": "Hansen TJ, Hodges E. ATAC-STARR-seq reveals transcription factor-bound activators and silencers within chromatin-accessible regions of the human genome. Genome research. 2022.", "doi": "10.1101/gr.276766.122", "pmcid": "PMC9435738", "url": "https://pubmed.ncbi.nlm.nih.gov/35858748/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35858748/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID35858748", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vivo cellular", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "ATAC-STARR reporter testing across about101000 accessible human regions finds30%with activator, silencer or both activity and similar silencer/activator frequencies.", "what_it_does_not_show": "Reporter regulatory potential is not native chromosomal competence or proof that the remaining70%cannot regulate under other conditions.", "confounders_present": [ "Reporter regulatory potential is not native chromosomal competence or proof that the remaining70%cannot regulate under other conditions." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 61, "pmid": "37557175", "title": "Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation.", "citation": "Brennan KJ, Weilert M, Krueger S et al. Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation. Developmental cell. 2023.", "doi": "10.1016/j.devcel.2023.07.007", "pmcid": "PMC10592203", "url": "https://pubmed.ncbi.nlm.nih.gov/37557175/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37557175/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID37557175", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Zelda motif-affinity pioneering and genetically validated patterning-factor activation generate two tiers of Drosophila enhancer accessibility.", "what_it_does_not_show": "Deep-model predictions require the reported genetic validation; accessibility and activation dependence are context-specific, not a universal pioneer classification.", "confounders_present": [ "Deep-model predictions require the reported genetic validation; accessibility and activation dependence are context-specific, not a universal pioneer classification." ], "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": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] } ], "verification_summary": { "load_bearing_claims_checked": 66, "verified": 66, "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": "Β", "cap_source": "universal", "triggered": true, "trigger_text_quoted": "Pure association evidence — however large, however replicated — cannot exceed Β.", "specific_trigger": "Accessibility and transcriptional state correlate extensively across original atlases, cell types and time courses. This existence subclaim is associational, with measurement scale, cell mixtures, motif sequence and transcriptional feedback affecting the correlation. Predictive accuracy does not establish causal direction.", "resulting_ceiling": "Β" }, { "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": "Acute endogenous remodeler perturbations and functional nascent-RNA readouts supply important mechanistic support. Yet they also perturb ATPase activity, transcription-factor occupancy, coactivator recruitment and nucleosome states; they do not establish that the accessible state as measured is universally necessary for transcriptional competence independently of those functions. The registered SC2 remains Γ. This does not mean physical DNA access is irrelevant or that remodelers lack endogenous causal effects.", "resulting_ceiling": "Γ" } ], "cap_precedence_resolutions": [ { "collision": "Perturbation in a defined setting versus broader inference", "subclaim_scope_cap_binds_on": "Chromatin accessibility determines transcriptional competence, such that accessible loci are those available for transcription.", "subclaim_scope_threshold_binds_on": "The precise experimentally tested subclaim scope", "resolution": "Endogenous factor/remodeler, locus-HAT and polymerase manipulations retain their actual causal scopes and are not re-capped as merely descriptive association. The nominal feature is measured accessibility itself: positive multifunctional mediator results cannot automatically cross its necessity threshold. Artificial TF expression, biochemical reconstitution, simulations and BAC transgenes retain universal/model limits. Direct opening-without-transcription and reverse-direction tests constrain specific nominal subclaims, not the existence of chromatin regulation generally. Nascent RNA is a functional transcription endpoint, rather than a disease biomarker, but global collapse controls remain necessary.", "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": [ "Genome-wide association and colocalization without direct perturbation cap at Β." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Accessibility and transcriptional state correlate extensively across original atlases, cell types and time courses. This existence subclaim is associational, with measurement scale, cell mixtures, motif sequence and transcriptional feedback affecting the correlation. Predictive accuracy does not establish causal direction.", "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": [ "Mechanistic plausibility plus in vitro reconstitution or simplified cellular support caps at Γ.", "No examined manipulation selectively removes the measured accessible state while preserving sequence-specific factor and coactivator functions across registered necessity scope." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Acute endogenous remodeler perturbations and functional nascent-RNA readouts supply important mechanistic support. Yet they also perturb ATPase activity, transcription-factor occupancy, coactivator recruitment and nucleosome states; they do not establish that the accessible state as measured is universally necessary for transcriptional competence independently of those functions. The registered SC2 remains Γ. This does not mean physical DNA access is irrelevant or that remodelers lack endogenous causal effects.", "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": [ "Opening-only insufficiency at a native locus is a falsification of general sufficiency, not a positive Δ crossing." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Opening alone is insufficient in a directly informative native-locus test: catalytic-dead dCas9-HAT restores asb11 accessibility in NPS-null zebrafish without restoring acetylation or transcription, while active HAT restores both. Promoter ATAC recovery above control also need not increase transcription above control. Positive active-HAT or ectopic-TF activation tests change more than opening. The broad sufficiency subclaim begins with Γ partial support and is downgraded one rung to Β by the specific opening-without-output falsification; Β is not a declaration that all opening is nonfunctional.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC4", "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": [ "Transcription-to-accessibility reversal in defined endogenous contexts falsifies a universal upstream direction." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Opening can precede transcription during zebrafish genome activation, but postreplication transcription restart, paused-polymerase/BAF cooperation and local ncRNA transcription can instead generate or stabilize accessibility. The registered general upstream direction therefore cannot be universal. Partial Γ directional support is downgraded one rung to Β for verified direction-reversal contexts, rather than describing them as merely missing evidence.", "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": "A causal subclaim needs an orthogonal locus-specific intervention rather than adding more atlas correlations; the correlation-existence claim itself does not require a higher causal level." }, { "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": "At native loci, independently reduce or restore measured accessibility while preserving sequence-specific factors, acetylation/coactivators and polymerase competence, then apply the same activating stimulus and measure initiation/bursting. Match rescue and verify cell cycle, replication stress, factor abundance and viability." }, { "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": "Prospectively define loci/cell states and selectively open them without recruiting activation domains or changing coactivator/histone activity, with matched opening controls and direct nascent-transcription readout. Include the known open-without-activation control and do not redefine scope as responsive loci." }, { "subclaim_id": "SC4", "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": "Establish time-resolved state-specific opening before initiation at native loci, separate pausing/initiation/elongation with orthogonal methods, and prospectively map developmental versus replication and stimulus contexts; retain reverse-direction counterexamples." } ], "generalization_check": { "generalization_tested": "yes", "context_boundary_mapped": "yes", "internal_negative_controls": [ "Catalytic-dead HAT restores asb11 opening without acetylation or transcription; active HAT and nontarget controls distinguish catalytic activation (PMID35182480).", "Accessibility recovers with expression at many EP400-compensated promoters, but above-control ATAC does not give broadly above-control transcription (PMID37922899).", "Most zebrafish early opening persists during alpha-amanitin inhibition, with miR430 as a specific exception (PMID31940339).", "RNAPII and BAF probe Polycomb-repressed regions; constitutive H3K9me3 heterochromatin differs (PMID38049663).", "Rapid BAF accessibility effects have few strong early PRO-seq changes, with detection/timing limits explicitly retained (PMID33558760).", "BRG1 dosage produces buffered transcription and different promoter/enhancer responses (PMID40846763).", "REST-dependent repression can require accessible PBAF sites (PMID40252649)." ], "note": "Locus sequence, factor identity, cell state, developmental/replication window, dose and observation interval are specified before results. Bulk accessibility and transient local DNA exposure differ. No subset is defined afterward as competent solely because it transcribes, and unresponsive open loci remain in the analysis. Zebrafish early priming and mammalian postreplication restart are both retained without forcing one global direction." }, "falsification_patterns_met": [ { "pattern": "Perturbing the proposed feature leaves the claimed output intact or opening fails to activate", "evidence": "SC3: catalytic-dead HAT restores opening without transcription at asb11 (PMID35182480), and elevated promoter ATAC does not produce broadly above-control transcription (PMID37922899). PreliminaryΓ→Β for broad sufficiency.", "downgrade_applied": true }, { "pattern": "Alternative direction contradicts universal upstream primacy", "evidence": "SC4: postreplication restart, polymerase/BAF pausing and upstream ncRNA transcription can generate/stabilize access (PMID31126739, PMID38049663, PMID18820678), while early zebrafish priming retains the opposite direction. PreliminaryΓ→Β for universal primacy.", "downgrade_applied": true } ], "pitfalls_flagged": [ { "pitfall": "Accessibility treated as competence", "where": "An assay peak is not a standardized response potential or an activation signal." }, { "pitfall": "Mediator necessity becomes state necessity", "where": "BRG1/BAF/TF loss changes multiple functions, even with acute timing controls." }, { "pitfall": "Universal direction inferred from one window", "where": "Zebrafish priming and mammalian postreplication restart have different causal ordering." }, { "pitfall": "Reporter or structural result promoted", "where": "BAC arrays, motif integrations, simulations and reconstituted nucleosomes retain model limits." }, { "pitfall": "Nascent and stable RNA conflated", "where": "Short perturbations can have large PRO-seq effects and small steady-state RNA changes." } ], "causal_tally_audit": { "tally_claimed_by_document": 0, "tally_after_audit": 0, "tally_unit": "Positive qualifying study units across scoped subclaims, not independent causal lines or full-claim necessity/sufficiency.", "screened_discriminating_contrasts": 53, "items_rejected": [ "Null and negative contrasts are discriminators, not positive threshold crossings. Reports and replications are not independent causal lines.", "Reports sharing participants, models or instruments are not independent causal lines.", "Pivotal nulls do not earn positive threshold crossings." ] }, "steelman": { "case_one_rung_higher": "One rung above, Δ: acute endogenous BRG1 or BAF loss rapidly reduces accessibility and nascent transcription without immediate viability collapse, and many promoters recover both through EP400. These are credible endogenous mediator effects. The blocker for registered SC2 is that DNA-state necessity has not been isolated from remodeler/TF/coactivator functions with a matched competence challenge and state-specific rescue.", "case_one_rung_lower": "One rung below, Β: accessible-state maps are correlated with transcription and many manipulations hit multifunctional factors. But endogenous time-resolved, calibrated perturbations and locus-specific controls supply substantial mechanistic content beyond atlas association, supporting Γ partial state-mechanism evidence.", "which_rejected": "Retain Γ for necessity with explicit separation from mediator causality. Reject both a universal open-locus transcription switch and a dismissal of endogenous remodeler/chromatin causal experiments.", "blocking_cap_threshold_or_missing_experiment": "Missing experiment: At prespecified native promoters/enhancers, alter DNA accessibility with an orthogonal state intervention while preserving factor occupancy, activation domains, acetylation/coactivators and polymerase function as far as possible. Apply a matched activating stimulus and measure initiation/bursting with calibrated nascent RNA and single-fiber accessibility. Restore only the accessible state in a matched rescue; retain a dead-HAT opening-without-activation control. Verify cell-cycle distribution, replication stress, viability, target-factor abundance and local cis sequence across developmental/replication windows." }, "final_score": { "hsef_level": "Γ", "hsef_descriptor": "Mechanistically plausible, partial system support", "confidence": "Moderate", "confidence_rationale": "Multiple independent studies across 61 primary reports with partial replication, but multifunctional perturbations, reporter rather than endogenous readouts and heterogeneous timing/dose controls remain; evidence density and reproducibility set the band, not reviewer access or correctness.", "rests_on_non_peer_reviewed_work": false, "rationale": "Overall Γ follows the preregistered primary necessity SC2: strong endogenous remodeler/factor causality exists, but necessity of the measured accessible state itself remains incompletely isolated. SC1 correlation is Β. Broad sufficiency SC3 and universal upstream SC4 are each Β after one-rung falsification downgrades from partial Γ. The alternative aggregation rules would return Β weakest-link and Γ primary/scope-matched." }, "role_of_mechanism": { "classification": "reinforcing / stabilizing factor", "derivation_step_matched": 5, "derivation": "Transcription can generate accessibility in some contexts, while factor/remodeler-dependent opening precedes and supports activation in others; the inventory does not support a purely downstream account everywhere. Co-variation alone is inadequate, but mediator and targeted state comparisons demonstrate mechanistic involvement. Universal accessible-state initiation/rate limitation and requirement are not independently established. Step5 therefore treats measured accessibility provisionally as a context-dependent supporting state in feedback with upstream factors and transcription, with the more specific permissive necessity model separately scored Γ.", "tournament_used_as_tiebreaker": false, "note": "Derived from causal direction, not tournament rank." }, "extended_scoring_MSD": { "momentum": { "value": "Mechanistic only", "artifact": "Recent BRG1 dosage/degron work (PMID40846763), native nucleosome-domain/fiber experiments (PMID42056506), PBAF/REST specificity (PMID40252649) and METTL3 accessibility-output uncoupling (PMID41135527) test mechanisms and state boundaries. They do not yet supply a selective universal accessible-state necessity experiment.", "justification": "Recent BRG1 dosage/degron work (PMID40846763), native nucleosome-domain/fiber experiments (PMID42056506), PBAF/REST specificity (PMID40252649) and METTL3 accessibility-output uncoupling (PMID41135527) test mechanisms and state boundaries. They do not yet supply a selective universal accessible-state necessity experiment." }, "stability": { "value": "Stable", "trigger": "No verified named pending state-selective necessity/rescue result was identified in this bounded search. A registered native-state perturbation with controlled activating challenge could raise SC2; further opening-only failures or reverse-direction studies could refine its scope.", "justification": "No verified named pending state-selective necessity/rescue result was identified in this bounded search. A registered native-state perturbation with controlled activating challenge could raise SC2; further opening-only failures or reverse-direction studies could refine its scope." }, "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": "No manufactured field consensus or arithmetic gap." }, "calibration_note": "M/S/D never modify HSEF level or confidence." }, "change_record": { "applies": false, "prior_level": "none assigned", "prior_confidence": null, "prior_source": null, "derived_before_consulting_prior": true, "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": "At prespecified native promoters/enhancers, alter DNA accessibility with an orthogonal state intervention while preserving factor occupancy, activation domains, acetylation/coactivators and polymerase function as far as possible. Apply a matched activating stimulus and measure initiation/bursting with calibrated nascent RNA and single-fiber accessibility. Restore only the accessible state in a matched rescue; retain a dead-HAT opening-without-activation control. Verify cell-cycle distribution, replication stress, viability, target-factor abundance and local cis sequence across developmental/replication windows.", "readout": "Direct nascent transcription/burst initiation after a matched competence challenge, alongside calibrated bulk and single-fiber DNA access", "critical_control": "State-specific matched rescue, target/untarget loci, catalytic-dead and recruitment controls, unchanged sequence/factor/coactivator abundance, cell cycle, replication stress, viability and timing", "supporting_result": "Selective closure blocks the prespecified response and restoring access alone rescues it without restoring other regulator functions; prospectively repeat across distinct native loci/states", "falsifying_result": "Adequate state manipulation leaves competence intact, restoration changes only assay signal, or output follows changed coactivator/factor function rather than the measured state" } ], "knowledge_gaps": [ { "name": "Gap 1", "statement": "A selective accessible-state necessity intervention must preserve the multifunctional regulators that establish it.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 2", "statement": "Competence requires a standardized activating challenge and cannot be inferred from either basal ATAC or basal RNA alone.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 3", "statement": "Bulk ATAC/DNase, methylase footprinting, local nucleosome distortion and large-scale decondensation measure different aspects of access.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 4", "statement": "Temporal direction depends on developmental, replication and stimulus context; a universal upstream or downstream account fails.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 5", "statement": "Specificity of factor/remodeler perturbations must exclude cell-cycle, viability, replication stress and transcriptional-collapse alternatives at each sampled time.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 6", "statement": "Opening-only sufficiency fails at named loci, while acetylation/coactivator rescue can work; these need independent locus/state replication.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 7", "statement": "Preprint/update duplication, shared reagents and repeated loci must be distinguished from independent error classes.", "relevance": "Limits mechanism identification or scope." } ], "review_metadata": { "review_date": "2026-10-12", "reviewer": "Codex", "evidence_base_note": "61 primary reports; literature cutoff 2026-10-09; source examination UTC date 2026-10-12; bounded critical review, not exhaustive systematic review.", "literature_tools_available": true, "literature_tools_note": "Life Sciences Literature PubMed/Entrez, separately logged public original-body retrieval, and Consensus Pro browser searches. Provider output retained as observed browser text with citation-link mappings, or as previously exported connector documents where present. AI synthesis is not primary full-text verification. Consensus retrieved/included counts are not examined-primary counts. Scite is queried per case where connected; received tallies/outgoing reference contexts are not audited incoming contrasting statements. Tool receipts record actual use. Supplementary discovery outputs do not earn primary-count credit. No independent blinded review.", "skill_version": "5.3", "validator_run": "PASS: exact archived HSEF v5.3 validator rerun after final sealing.", "validator_warnings_addressed": "No warnings.", "limits": "Bounded source-based critical review; no complete-paper/supplement audit, independent scientific peer review or blinded calibration. Revision cases retain original prose outside the three framework output blocks and have explicit correction logs." }, "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": "Orthogonal endogenous degrons and ATPase inhibitors, factor-domain/motif contrasts, targeted HAT rescue, nascent-RNA assays, calibrated single-fiber state measurements and allele-associated regulatory variants were considered. These establish valuable mediator mechanisms in different contexts, but not independent same-scope necessity of accessibility alone. Higher levels remain reachable with a selective endogenous state manipulation and prespecified competence challenge rather than more ATAC correlation." }, { "kind": "natural_experiment", "available": false, "why_not_sufficient": "Orthogonal endogenous degrons and ATPase inhibitors, factor-domain/motif contrasts, targeted HAT rescue, nascent-RNA assays, calibrated single-fiber state measurements and allele-associated regulatory variants were considered. These establish valuable mediator mechanisms in different contexts, but not independent same-scope necessity of accessibility alone. Higher levels remain reachable with a selective endogenous state manipulation and prespecified competence challenge rather than more ATAC correlation." }, { "kind": "dose_response_across_populations", "available": false, "why_not_sufficient": "Orthogonal endogenous degrons and ATPase inhibitors, factor-domain/motif contrasts, targeted HAT rescue, nascent-RNA assays, calibrated single-fiber state measurements and allele-associated regulatory variants were considered. These establish valuable mediator mechanisms in different contexts, but not independent same-scope necessity of accessibility alone. Higher levels remain reachable with a selective endogenous state manipulation and prespecified competence challenge rather than more ATAC correlation." }, { "kind": "withdrawal_rechallenge", "available": false, "why_not_sufficient": "Orthogonal endogenous degrons and ATPase inhibitors, factor-domain/motif contrasts, targeted HAT rescue, nascent-RNA assays, calibrated single-fiber state measurements and allele-associated regulatory variants were considered. These establish valuable mediator mechanisms in different contexts, but not independent same-scope necessity of accessibility alone. Higher levels remain reachable with a selective endogenous state manipulation and prespecified competence challenge rather than more ATAC correlation." }, { "kind": "therapeutic_perturbation_hard_endpoint", "available": false, "why_not_sufficient": "Orthogonal endogenous degrons and ATPase inhibitors, factor-domain/motif contrasts, targeted HAT rescue, nascent-RNA assays, calibrated single-fiber state measurements and allele-associated regulatory variants were considered. These establish valuable mediator mechanisms in different contexts, but not independent same-scope necessity of accessibility alone. Higher levels remain reachable with a selective endogenous state manipulation and prespecified competence challenge rather than more ATAC correlation." } ], "convergence_present": false, "cap_reapplied_to_convergent_set": false }, "provenance_header": { "sources_total": 61, "claims_total": 66, "claims_verified": 66, "claims_unverified": 0, "claims_contradicted": 0, "tier_a_sources": 61, "generated_by": "Codex; HSEF v5.3", "gate_passed": true }, "claims": [ { "id": "C1", "text": "Endogenous BRG1-AID depletion reduces nascent RNA, RNAPII occupancy and DHS accessibility in primary mouse cells without measured viability/growth defects. BRG1 loss also changes nucleosomes, p300 and acetylation; it does not selectively remove accessible state while preserving other mediator functions.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 1 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Results:paragraph0, 1:Results:paragraph2, 1:Results:paragraph7, 1:Results:paragraph14. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C2", "text": "Acute ARID1A degron causes rapid accessibility/EP300 changes but comparatively few early differentially expressed genes; later adaptive transcript changes dominate. EP300 redistribution and multifactor effects prevent accessibility-specific necessity; steady-state RNA and timing affect apparent coupling.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 2 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C3", "text": "dTAG, ATPase inhibition and degradation rapidly alter BAF-dependent accessibility with smaller early PRO-seq changes under nontoxic inhibitor conditions. dTAG clone begins with about50%SMARCA4 and baseline changes; rapid accessibility loss is not a selectively isolated state perturbation or immediate global loss of transcription.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 3 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 0:Results:paragraph0, 0:Results:paragraph1, 0:Results:paragraph5, 0:Results:paragraph6. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C4", "text": "Chemical-genetic time courses show paused RNAPII stabilizes BAF occupancy and ATPase-dependent eviction; TF binding confers locus specificity. Inhibition changes transcription machinery directly;≤2htriptolide viability controls do not extend to4h, and bidirectional synergy is not universal upstream opening.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 4 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Results:paragraph2, 1:Results:paragraph3, 1:Results:paragraph9, 1:Results:paragraph14. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C5", "text": "Fast SWISNF inhibition reduces accessibility/transcription; EP400 restores promoter accessibility and expression during prolonged inhibition, with no toxicity in early windows. Above-control ATAC recovery need not increase transcription above control; factor activity and state remain coupled despite orthogonal inhibitor/degrader/EP400 tests.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3", "SC4" ], "source_ns": [ 5 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:RESULTS:paragraph1, 1:RESULTS:paragraph2, 1:RESULTS:paragraph6, 1:RESULTS:paragraph8, 1:RESULTS:paragraph25, 1:RESULTS:paragraph26. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C6", "text": "Dose-graded BRG1 degradation reveals enhancer-specific accessibility and buffered transcription with promoters/insulators often unaffected. Protein dosage tests multifunctional remodeler, not accessible state alone; nonlinear buffering defeats one-to-one competence inference.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 6 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C7", "text": "p300/CBP catalytic activity controls rapid PIC/RNAPII recruitment and pause release while TF/coactivator recruitment persists. This isolates acetylation-dependent activation, not accessibility-only necessity; original body was not publicly retrieved in this audit.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 7 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C8", "text": "OCT4 loss and BRG1 requirement constrain endogenous mouseESC binding, accessibility and pluripotency transcription. Factor/remodeler functions and cell-state regulation are not independent accessible-state manipulation.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 8 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C9", "text": "Zebrafish regulatory opening precedes transcription and persists under alpha-amanitin except miR430; maternal-factor loss reduces opening. Priming is not sufficient activation; transcription independence in this window is not universal across replication/cell states, and nearest-neighbor enhancer links are inferred.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3", "SC4" ], "source_ns": [ 9 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Results:paragraph2, 1:Results:paragraph4, 1:Results:paragraph7, 1:Results:paragraph12. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C10", "text": "NPS-null zebrafish have lost enhancer opening; locus dCas9 active HAT restores transcription, while catalytic-dead HAT restores opening without transcription at asb11. Clean opening-without-activation discriminates sufficiency but does not prove a universal necessity of measured ATAC; targetedHAT also changes acetylation/cofactor recruitment.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 10 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Results:paragraph1, 1:Results:paragraph7, 1:Results:paragraph8. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C11", "text": "Postreplication transcription restart is required to restore active chromatin accessibility in mouseESCs by repli-ATAC and transcription inhibition. Replication-conditioned restoration is not every locus/state; linked erratum PMID31348880 was identified but its details were not read.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 11 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C12", "text": "Fiber-seq resolves polymerase/nucleosome footprints and pausing-dependent nucleosome destabilization/coupling on individual Drosophila fibers. Single-fiber structure and perturbation address transcription-to-chromatin feedback, not opening as an independent universal competence determinant.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 12 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C13", "text": "Experiments/simulations show OCT4 stabilizes flexible/open nucleosome conformations depending on motif position and histone tails. Structural binding does not establish endogenous transcript necessity or sufficiency.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 13 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C14", "text": "Molecular simulations predict nucleosome breathing/twisting and partial-motif recognition permit OCT4 binding. Computation is original research but no functional causal transcription crossing or direct endogenous measurement.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 14 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C15", "text": "Hormone-induced GR binds both preaccessible and nucleosomal/inaccessible enhancer classes and recruits BRG1 with shifts. GR/BRG1 perturbation and hormone exposure do not isolate accessibility state; nucleosomal and DNase sensitivity are not interchangeable.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 15 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C16", "text": "Androgen time courses support GATA2 binding at inaccessible nucleosome edges before remodeling and downstream regulation. Multifactor binding/state changes do not establish opening-only competence or generalize from LNCaPcells.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 16 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C17", "text": "GATA3 activation-domain deletion retains binding but prevents productive remodeling/MET; some bound loci slide nucleosomes without becoming accessible. Ectopic reprogramming and lost recruitment functions do not establish endogenous accessible-state necessity.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 17 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C18", "text": "HumanESC differentiation profiles show motif/context-dependent TF nucleosome binding, including at accessible loci. Computational occupancy classification and time course do not selectively test necessity or sufficiency.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 18 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C19", "text": "PARP1 cooperates with Sox2 nucleosome binding independently of catalytic activity at selected nativeESC loci. Specific protein cooperation supports pioneer access but does not isolate opening from Sox2/cofactor regulation.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 19 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C20", "text": "Ectopic FOXA1 and HNF4A each bind/open sites and activate genes, without a general sequential pioneer/nonpioneer distinction. Overexpression is capped for endogenous function; demonstrates TF/context dependence rather than opening-alone sufficiency.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 20 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C21", "text": "Esrrb binds silenced enhancers and recruits core factors with demethylation/p300/nucleosome changes during reprogramming. Ectopic reprogramming and LIF/cofactor dependence constrain endogenous generalization; linked erratum PMID30526884 details unexamined.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 21 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C22", "text": "Ectopic deltaNp63 binds inaccessible/unmodified nucleosome edges and induces acetylation/repositioning. Engineered expression and nucleosome assays do not establish endogenous state necessity or universal activation.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 22 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C23", "text": "Induced GATA3 productive/unproductive sites differ in cooperating factors; SWISNF ATPase inhibition removes induced accessibility/binding. EctopicTF, remodeler functions and context dependence prevent an opening-only claim.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 23 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C24", "text": "Live Drosophila transcription dynamics reject tested thermodynamic/MWC accessibility models and fit factor-catalyzed models better. Predictive model fit is not a direct selective measurement or necessity test of the accessible state.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 24 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C25", "text": "Single-fiber footprinting and TF-domain/genetic contrasts show regulated nucleosome distortion across mouse/human differentiation contexts. TF-domain perturbation affects more than accessibility; distorted nucleosomes are not equivalent to bulk nucleosome-free ATAC peaks or direct activation.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 25 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C26", "text": "G4formation persists under initiation/elongation inhibition; compaction removes promoterG4/PolII and G4ligand partly preserves PolII. Compaction/ligand have multiple effects and do not isolate accessibility fromG4/protein recruitment; no universal direction.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 26 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C27", "text": "Polymerase degrons have modest early3D effects but longer PolII loss changes accessibility/cohesin. Time-dependent indirect effects and architecture/transcription/readout differences constrain direction claims.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 27 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C28", "text": "Translation inhibition rapidly changes unstable euchromatin regulators, RNAPII and accessibility inESCs/blastocysts. Global translation/growth stress is not accessibility-specific perturbation and can explain multiple endpoints.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 28 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C29", "text": "Hsf1 nuclear depletion/nascentRNA reveal factor-dependent transcription; heat-shock binding/disassembly differs across nucleosomal contexts. Heat stress and RSC/factor interactions do not isolate accessibility-only necessity; basal and induced contexts differ.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 29 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C30", "text": "Primary human-cancer ATAC and multiomics reveal tissue/subtype-specific regulatory elements and expression links. Bulk cell mixtures and inferred enhancers/links are observational, not competence necessity.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 30 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C31", "text": "Single-cell mouse tissue accessibility atlas maps cell-type regulatory patterns and inferred expression relationships. Atlas co-variation and crossmodal mapping do not selectively test causality.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 31 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C32", "text": "Single-cell ATAC reveals regulatory variability associated with factors and stimulus/cell-cycle perturbations. Accessibility variability is not a direct transcript competence assay; signaling/cell cycle can confound coupling.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 32 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C33", "text": "Human fetal gene-expression/accessibility atlases map cell-type-specific candidate regulatory elements. Atlas integration and motif/heritability enrichment are not selective causal dependency.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 33 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C34", "text": "Joint perturbation-accessibility-transcript profiling identifies differentiation regulators andZNHIT1in pediatric cancer. Gene knockout perturbs multifunctional regulators; shared-cell modalities do not themselves isolate state mediation.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 34 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C35", "text": "Integrated Arabidopsis root nucleusRNA/ATAC maps cell-type marker/accessibility patterns. Species-specific atlas associations support correlation, not causal necessity or sufficiency.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 35 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C36", "text": "METTL3 loss/degron and RNA editing reveal retinal transcription regulation with direct chromatin targets showing weak accessibility-output correlation. RNA stability/m6A are alternative mediators; uncoupling does not prove no locus ever depends on accessibility.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 36 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C37", "text": "ANP32E loss changesH2AZpositioning, accessibility, TFbinding and neighboring expression in fibroblasts. Histone-variant/remodeler functions and broad perturbation do not isolate accessible state from other regulatory inputs.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 37 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C38", "text": "CRISPR-sciATAC perturbations map remodeler-specific accessibility, withEZH2loss/HOXexpression examples. Chronic gene knockouts and state changes are not accessibility-only endogenous necessity tests.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 38 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C39", "text": "Human livercaQTLs identify allele-associated accessibility and aLITAFvariant has allele-specific binding/transcription activity. Small tissue cohort, inferredgene links and alteredTFsequence confound accessibility mediation; not a pure state instrument.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 39 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C40", "text": "HOX13 function is required for distal-limb accessibility and permitsHOXA11target binding in engineered limbs. DevelopmentalTFloss/ectopicHOXA11has multiple regulatory effects; independent accessibility-state necessity remains untested.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 40 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C41", "text": "Engineered SOX9 reactivation opens hair-follicle enhancers and redistributes cofactors away from epidermal programs, inducing fate switching. Sustained ectopic TF and cofactor competition do not prove accessibility-only activation or normal endogenous scope.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 41 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C42", "text": "ETV2 binds nucleosomal DNA and recruits BRG1 during engineered endothelial differentiation/reprogramming. TF/remodeler/acetylation coupled functions and engineered state restrict necessity and generalization.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 42 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C43", "text": "Pax7 DNA-binding domain/motif mutants separate high-affinity pioneering from low-affinity heterochromatin binding. DNA-binding/domain changes do not selectively remove accessibility while preserving activator functions.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 43 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C44", "text": "Endogenous tagging/live imaging shows Zelda/coactivator/RNAPII cluster cascade before transcription and dispersal during elongation. Cluster timing is not direct accessible-state necessity; imaging alone does not prove condensate mechanism.", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 44 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C45", "text": "Near-endogenous-level transcription occurs on condensed multimegabase BAC transgene fibers with modest induced extension. BAC arrays and large-scale compaction are not endogenous local ATAC state; evidence cannot disprove all microscopic access requirements.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 45 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C46", "text": "Mechanical strain upregulates DHFR BAC transgene transcription with direction/actomyosin controls. Reporter and force-mediated nuclear inputs do not establish accessibility-only endogenous sufficiency.", "carries_number": false, "load_bearing_for": [ "SC3", "SC4" ], "source_ns": [ 46 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C47", "text": "An endogenous fission-yeast fbp1 upstream transcription terminator blocks the ncRNA cascade and subsequent chromatin opening/activation. Inserted terminator changes local cis context; locus-specific transcription-to-opening is not every genome's direction.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 47 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C48", "text": "Systematic integrated yeast motifs identify 29 nucleosome-displacing factors with binding-affinity/replication dependence. Synthetic locus/motif context and occupancy endpoint are not endogenous general competence necessity.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 48 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C49", "text": "Defined chromosomal locus/nucleosome positioning shows TF-specific access; some factors invade internal sites and displace nucleosomes. Engineered motifs demonstrate binding specificity, not accessibility-state-only endogenous output causality.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 49 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C50", "text": "Genetic/chemical variant-specific SWI/SNF perturbations map inflammatory versus interferon transcription requirements in macrophages. Signal-dependent factor/complex functions, rather than generic accessible state, carry specificity.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 50 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C51", "text": "PBAF/ARID2 loss impairs REST binding and repression, showing accessibility can support a silencing factor. Multifunctional complex loss does not isolate accessible-state necessity; opening need not imply activation.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 51 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C52", "text": "Single-molecule reconstitution shows Rap1 invades nucleosomes and cooperates with RSC for displacement. Purified chromatin-fiber mechanism is Γ-limited for endogenous transcription necessity.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 52 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C53", "text": "CLOCK/BMAL1 rhythmic binding/nucleosome changes recruit other factors with heterogeneous output. Rhythmic coupling and TF intervention do not isolate accessibility from clock regulation.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 53 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C54", "text": "PU.1 cannot access nucleosomal motifs in vitro but ectopic pioneering depends on activation-domain/SWI/SNF recruitment. Ectopic expression and specific protein functions restrict native-state causality; linked erratum PMID32098963 details unexamined.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 54 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C55", "text": "HMGN1 overexpression increases accessibility/stem-cell activity and cooperates with an AML fusion; HAT inhibition relieves the differentiation block. Overexpression, leukemia mutation and histone effects cannot prove a generic accessible-state driver.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 55 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C56", "text": "GR uses mostly preaccessible FOXA1 sites in resistant prostate cells; FOXA1 silencing increases GR activity through NR3C1 de-repression. Factor-abundance repression and p300 activity explain output; preaccess alone does not dictate receptor transcription.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 56 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C57", "text": "Targeted dCas9-p300 core acetylation activates endogenous promoter/enhancer target genes with specificity. Catalytic acetylation/coactivator recruitment is more than opening; artificial tethering is not accessibility-only sufficiency.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 57 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C58", "text": "Combined VPR/p300 epigenetic/transcriptional effectors enhance endogenous gene activation with off-target characterization. Composite engineered activators cannot isolate accessible-state sufficiency and retain off-target concerns.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 58 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C59", "text": "BRG1 AT-hook/eRNA association and perturbations link stage-specific SWI/SNF recruitment with enhancer/coactivator activation. RNA binding/transcriptional inputs and factor functions remain coupled; this is not universal upstream opening or generic competence.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 59 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C60", "text": "ATAC-STARR reporter testing across about101000 accessible human regions finds30%with activator, silencer or both activity and similar silencer/activator frequencies. Reporter regulatory potential is not native chromosomal competence or proof that the remaining70%cannot regulate under other conditions.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 60 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C61", "text": "Zelda motif-affinity pioneering and genetically validated patterning-factor activation generate two tiers of Drosophila enhancer accessibility. Deep-model predictions require the reported genetic validation; accessibility and activation dependence are context-specific, not a universal pioneer classification.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3", "SC4" ], "source_ns": [ 61 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "CSC1", "text": "Accessibility and transcriptional state correlate extensively across original atlases, cell types and time courses. This existence subclaim is associational, with measurement scale, cell mixtures, motif sequence and transcriptional feedback affecting the correlation. Predictive accuracy does not establish causal direction.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 8, 9, 12, 15, 16, 18, 24, 25, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 44, 53, 60, 61 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-12", "note": "" }, { "id": "CSC2", "text": "Acute endogenous remodeler perturbations and functional nascent-RNA readouts supply important mechanistic support. Yet they also perturb ATPase activity, transcription-factor occupancy, coactivator recruitment and nucleosome states; they do not establish that the accessible state as measured is universally necessary for transcriptional competence independently of those functions. The registered SC2 remains Γ. This does not mean physical DNA access is irrelevant or that remodelers lack endogenous causal effects.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 34, 36, 37, 38, 39, 40, 41, 42, 43, 45, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 61 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-12", "note": "" }, { "id": "CSC3", "text": "Opening alone is insufficient in a directly informative native-locus test: catalytic-dead dCas9-HAT restores asb11 accessibility in NPS-null zebrafish without restoring acetylation or transcription, while active HAT restores both. Promoter ATAC recovery above control also need not increase transcription above control. Positive active-HAT or ectopic-TF activation tests change more than opening. The broad sufficiency subclaim begins with Γ partial support and is downgraded one rung to Β by the specific opening-without-output falsification; Β is not a declaration that all opening is nonfunctional.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 5, 7, 9, 10, 17, 20, 21, 23, 41, 46, 51, 55, 56, 57, 58, 60, 61 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-12", "note": "" }, { "id": "CSC4", "text": "Opening can precede transcription during zebrafish genome activation, but postreplication transcription restart, paused-polymerase/BAF cooperation and local ncRNA transcription can instead generate or stabilize accessibility. The registered general upstream direction therefore cannot be universal. Partial Γ directional support is downgraded one rung to Β for verified direction-reversal contexts, rather than describing them as merely missing evidence.", "carries_number": false, "load_bearing_for": [ "SC4" ], "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, 34, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 56, 57, 59, 61 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-12", "note": "" }, { "id": "CH", "text": "Accessible chromatin predicts regulatory activity, but access alone neither guarantees transcription nor supplies a universal upstream mechanism of competence.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 1, 5, 10, 9, 11, 4 ], "verification": "verified", "verified_against": "Bounded synthesis of examined sources; score is adjudication.", "verified_on": "2026-10-12", "note": "" } ], "citation_ledger": [ { "n": 1, "citation": "Ren G, Ku WL, Ge G et al. 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The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells. eLife. 2017.", "tier": "A", "kind": "primary", "pmid": "28287392", "doi": "10.7554/eLife.22631", "url": "https://pubmed.ncbi.nlm.nih.gov/28287392/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID28287392", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C8", "CSC1", "CSC2", "CSC4" ] }, { "n": 9, "citation": "Pálfy M, Schulze G, Valen E et al. Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation. 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No complete-paper or supplement audit claimed.", "carries_claims": [ "C61", "CSC1", "CSC2", "CSC3", "CSC4" ] } ], "independence_basis": { "required": false, "lines": [ { "label": "Acute remodeler and dosage perturbation", "sources": [ 1, 3, 5, 6 ], "excludes_error": "Reduce chronic adaptation and selected viability alternatives, while shared ATPase/complex functions still confound state mediation." }, { "label": "Developmental factor loss and targeted catalytic rescue", "sources": [ 9, 10, 8 ], "excludes_error": "Constrain sequence-factor/coactivator mechanisms and opening-only sufficiency; developmental settings and artificial targeted constructs retain scope." }, { "label": "Transcription-stage and replication direction tests", "sources": [ 4, 11, 47, 12 ], "excludes_error": "Constrain a universal upstream-opening account using different timing/locus/fiber assays; broad inhibitor and local cis effects remain." }, { "label": "Single-cell/fiber and genetic measurement", "sources": [ 30, 33, 25, 39 ], "excludes_error": "Constrain broad correlations and assay scale, not accessibility-specific necessity or sufficiency." } ], "shared_failure_mode_checked": true, "note": "Assay classes and systematic failure modes are distinguished. Replicate loci, degron/inhibitor versions of one mediator and multiple papers from one factor/cell resource do not by themselves create independent causal lines. Zebrafish NPS reports share factors/developmental system, though the targeted-HAT experiment adds a different discriminator. A preprint and its published/update version count once.61 reports are not59independent mechanisms." }, "consensus_validation": { "completed": true, "status": "completed_original_source_reconciliation", "provider_mode": "Consensus Pro signed-in browser; observed output and citation link mappings", "queries": [ "https://consensus.app/search/chromatin-accessibility-and-transcription/ff6CXBaQQI6HAWL-Q4BnoQ/" ], "query_record_note": "Exact visible question/response retained privately in raw browser receipt.", "primary_comparison_count": 8, "primary_comparisons": [ { "pmid": "37922899", "doi": "10.1016/j.cell.2023.10.006", "source_type": "primary study report", "study_group": "PMID37922899", "access_depth": "full_text_partial", "consensus_aspect": "EP400 compensation: accessibility and expression recovery", "result_comparison": "Provider said this original was unavailable. Actual original Results1/2/6/8/25/26 show early SWI/SNF inhibition loses accessibility and transcription; EP400 restores both at many promoters. Above-control ATAC in clusters3/4 does not yield broadly above-control transcription. 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Hypertranscribed miR430 loses opening, a specific exception. No universal statement that all accessibility requires transcription or that transcription is irrelevant is justified.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/31940339/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\chromatin-accessibility\\examinations\\original-0-12-4500.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\chromatin-accessibility\\body-presentation-receipts\\31940339-s1-p2-4-7-12.json" ] }, { "pmid": "35182480", "doi": "10.1016/j.molcel.2022.01.024", "source_type": "primary study report", "study_group": "ZEBRAFISH_NPS_TARGETED_RESCUE_2022", "access_depth": "full_text_partial", "consensus_aspect": "Catalytic-dead HAT separates opening from activation", "result_comparison": "Provider describes active-HAT bypass but omits the decisive control. 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HAT bypass does not mean opening itself is sufficient or bypassed.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/35182480/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\chromatin-accessibility\\examinations\\original-0-12-4500.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\chromatin-accessibility\\body-presentation-receipts\\35182480-s1-p1-7-8.json" ] }, { "pmid": "38049663", "doi": "10.1038/s41588-023-01603-8", "source_type": "primary study report", "study_group": "BAF_RNAPII_COOPERATION_PUBLISHED", "access_depth": "full_text_partial", "consensus_aspect": "Transcription-stage drugs and viable time windows", "result_comparison": "Original Results2/3/9/14 support paused RNAPII stabilizing BAF and ATPase-dependent nucleosome eviction. Triptolide shows no morphology/viability change up to2hours but defects at4hours, so early controlled evidence cannot license all late samples. PRC2-repressed and H3K9me3 constitutive regions differ.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/38049663/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\chromatin-accessibility\\examinations\\original-0-12-4500.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\chromatin-accessibility\\body-presentation-receipts\\38049663-s1-p2-3-9-14.json" ] }, { "pmid": "38811575", "doi": "10.1038/s41467-024-48911-z", "source_type": "primary study report", "study_group": "PMID38811575", "access_depth": "full_text_partial", "consensus_aspect": "Acute BRG1 interpretation and changed-site denominator", "result_comparison": "Original Results0/2/7/14 confirm endogenous AID baseline controls, nascent versus stable-RNA differences, and cross-cell-state experiments. Provider's96%figure concerns changed DHSs, not every DHS in the genome. Drug-treatment text and figure captions differ between10and12hours; no invented unified time is used.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/38811575/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\chromatin-accessibility\\examinations\\original-0-12-4500.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\chromatin-accessibility\\body-presentation-receipts\\38811575-s1-p0-2-7-14.json" ] }, { "pmid": "33558760", "doi": "10.1038/s41588-021-00777-3", "source_type": "primary study report", "study_group": "PMID33558760", "access_depth": "full_text_partial", "consensus_aspect": "Fast ATAC effects versus early transcription and tag baseline", "result_comparison": "Provider omitted this original. Actual Results0/1/5/6 verify rapid degron/inhibitor effects and nontoxic inhibitor controls, but the dTAG clone starts with approximately50%SMARCA4 and altered baseline. Few strong early PRO-seq changes do not demonstrate immediate global transcription loss or refute later dependency.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/33558760/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\chromatin-accessibility\\examinations\\original-0-12-4500.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\chromatin-accessibility\\body-presentation-receipts\\33558760-s0-p0-1-5-6.json" ] }, { "pmid": "35858748", "doi": "10.1101/gr.276766.122", "source_type": "primary study report", "study_group": "PMID35858748", "access_depth": "abstract_metadata", "consensus_aspect": "Reporter activity within accessible regions", "result_comparison": "Original abstract verifies roughly101000accessible regions and30%containing an activator, silencer or both. Provider numbers are retained only as the reporter assay's result. The remaining70%are not proved incompetent endogenous loci, and accessible silencers need not activate their own genomic transcription.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/35858748/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\chromatin-accessibility\\examinations\\original-59-61-6000.json" ], "body_receipts": [] }, { "pmid": "37557175", "doi": "10.1016/j.devcel.2023.07.007", "source_type": "primary study report", "study_group": "PMID37557175", "access_depth": "abstract_metadata", "consensus_aspect": "Pioneering versus enhancer activation and publication date", "result_comparison": "Original2023published abstract, rather than provider2022label, reports genetically validated Zelda-dependent priming and additional patterning-factor activation. This supports separate tiers; computational fit alone does not prove state causality.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/37557175/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\chromatin-accessibility\\examinations\\original-59-61-6000.json" ], "body_receipts": [] } ], "grade_changed": false, "grade_change_note": "Source-based adjudication; no independent blinded regrade claimed.", "raw_receipts": [ { "path": "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\chromatin-accessibility\\consensus-browser-2026-10-12.json", "sha256": "6f8ec3b86ee1301a941208dda779c788b5f9ff011efca717393f63d6fbc99467" } ], "independent_blinded_audit": false, "cutoff": "2026-10-09", "completed_utc": "2026-10-12T20:10:21.496719+00:00", "conclusion": "Endpoint hierarchy, experimental scope and original-source limits determine the evidence cards; provider wording does not override them." } }