Nature communicationsOct 30, 2026

Changes in 3D DNA contacts predict shifts in gene regulation when cohesin is reduced

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Nov 2, 2026

Abstract

Analysis of 1039 candidate enhancers identified 30 significant enhancer-gene pairs, with 16 showing cohesin-dependent effects.

Cohesin depletion leads to limited changes in gene expression, despite widespread loss of contact domains.
Only distal enhancers (greater than 50 Kb away) were cohesin-dependent, but not all distal enhancers were affected.
Changes in enhancer effects were correlated with alterations in 3D contact frequency between enhancers and promoters.
The impact of cohesin on enhancer function varies based on genomic distance and other specific factors.
Most predicted enhancer-gene interactions do not display significant contact changes when cohesin is depleted.

Simplified

Enhancers are drivers of gene regulation thought to act via 3D interactions with promoters. However, genome-wide cohesin depletion causes only limited changes in gene expression, despite widespread loss of contact domains, raising questions about how 3D contacts and cohesin influence enhancer function. Here, we introduce CRISPRi of regulatory elements upon degron operation (CRUDO), to quantitatively assess how changes in contact frequency affect enhancer-driven gene regulation. We analyzed 1039 candidate enhancers near five cohesin-dependent genes and identified 30 significant enhancer-gene pairs, 16 with cohesin-dependent effects. While all cohesin-dependent enhancers were distal (>50 Kb), not all distal enhancers were sensitive to cohesin. Instead, changes in enhancer effects correlated with changes in enhancer-promoter 3D contact frequency, which appeared to depend on both genomic distance and other locus-specific factors. Across the genome, most predicted enhancer-gene regulatory interactions do not show substantial contact changes upon cohesin depletion, explaining why only a small subset of genes are cohesin-sensitive. Together, our results illuminate how 3D contacts tune enhancer effects on endogenous gene expression.

Full Text

Full text is available at the source.

View Full Text ↗

Changes in 3D DNA contacts predict shifts in gene regulation when cohesin is reduced

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the crispr gene editing brief