# Consensus checked against original sources: Enhancer–Promoter Looping as Causal

Cutoff: 9 October 2026. Consensus supports discovery and checks of specific source aspects; it is not a primary study, a full-paper audit or a causal probability meter.

## Engineered functional sufficiency, not natural continuous necessity
The original native-globin experiment supports activation by an active LDB1 tether with enhancer-dependent allele controls. Consensus correctly identifies a functional forced-looping result. The target gene is endogenous, but the recruited protein construct is synthetic; this does not prove geometry alone sufficient or contact continuously necessary. [Original PMID22682246](https://pubmed.ncbi.nlm.nih.gov/22682246/). Access: full_text_partial.

## Burst fraction differs from live burst frequency
The original Results confirm increased snapshot burst fraction without increased burst size after forced contacts. The paper explicitly reserves definitive competing-contact dynamics for direct live imaging. Consensus's frequency language must therefore distinguish inferred likelihood from measured initiation frequency. [Original PMID27067601](https://pubmed.ncbi.nlm.nih.gov/27067601/). Access: full_text_partial.

## Sox2 spatial decoupling within measured resolution
The original same-cell imaging finds no contemporaneous or tested lag-window proximity relation to enhancer-dependent bursts. Original labels are offset by kilobases, and reporter delays and finite resolution leave brief or earlier contacts possible. The provider's initial categorical no-contact wording is too broad; its later targeted answer recognizes this limitation. Canonical original publication is 2019, despite provider 2018 labels. [Original PMID31124784](https://pubmed.ncbi.nlm.nih.gov/31124784/). Access: full_text_partial.

## Neural Shh enhancers are not the limb ZRS
The original Results examine brain enhancers during neural differentiation and embryonic neural tissue. Activation increases measured separation, with a synthetic-loop positive imaging control. Consensus initially mislabels this as a limb-enhancer finding and cannot retrieve the exact paper in its targeted answer. The original body corrects the anatomy and preserves the fixed-assay limitation. [Original PMID31494034](https://pubmed.ncbi.nlm.nih.gov/31494034/). Access: full_text_partial.

## Architectural loss retains most enhancer contacts
The original Results show approximately 80% of enhancer-promoter contacts remain unaltered after acute CTCF/cohesin depletion, while short-term gene changes are modest. This is an extrusion-factor maintenance test, not selective elimination of every productive contact. The targeted provider correctly cautions about retained contacts but did not validate this exact paper itself. [Original PMID36471071](https://pubmed.ncbi.nlm.nih.gov/36471071/). Access: full_text_partial.

## Correct original year and loop-competent mutant
The original 2014 paper restores globin looping with LDB1 DD4/5 deletion without restoring transcription or polymerase recruitment. Consensus's exact-paper search failed and relied on 2013-labeled title surrogates. The original result separates looping from downstream activation chemistry; it does not prove all contacts unnecessary. [Original PMID24874989](https://pubmed.ncbi.nlm.nih.gov/24874989/). Access: full_text_partial.

## The 2022 graded landscape is a distinct publication
The original 2022 study uses an ectopic regulatory landscape and largely founder-line contact probabilities to fit nonlinear promoter on-rate behavior. It is distinct from the 2026 live burst-cluster paper. Consensus's conditional conflation of the papers is corrected; neither proves universal continuous native-locus contact necessity. [Original PMID35418676](https://pubmed.ncbi.nlm.nih.gov/35418676/). Access: full_text_partial.

## Conditional macrophage deletion is not acute degradation
The original Methods/Results use conditional Rad21 deletion in quiescent macrophages, with cell-cycle and damage checks. Burst participation is uncoupled despite similar measured enhancer-promoter distances at several loci. Consensus called this acute degradation; the original experiment corrects the intervention identity and retains resolution limitations. [Original PMID35896525](https://pubmed.ncbi.nlm.nih.gov/35896525/). Access: full_text_partial.

## Methods
Consensus was used to identify literature and cross-check specific claims about design, endpoints, scope and research gaps. Those aspects were checked against original primary abstracts/status records and selected original Methods/Results passages. Consensus output was not treated as original full text. Provider search omissions are not evidence that a study does not exist. Source access and examination receipts are retained. Scite use or monthly unavailability is recorded per case; provider citation counts do not change causal grades.