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Histone Acetylation Differentially Modulates CTCF-CTCF Loops and Intra-TAD Interactions
Journal article   Open access   Peer reviewed

Histone Acetylation Differentially Modulates CTCF-CTCF Loops and Intra-TAD Interactions

Rebecca G. Smith, Yu Fu, Kathleen L. Schiela, Madison Dautle, Ryan A. Williams, Hannah M. Wilson, Chloe Azadegan, Johnathan R. Whetstine, Job Dekker and Yu Liu
Nature communications, v 17(1), 6676
20 Jul 2026
DOI: https://doi.org/10.1038/s41467-026-75818-8
PMID: 42476989
url
https://doi.org/10.1038/s41467-026-75818-8View
Published, Version of Record (VoR) Open

Abstract

45 45/15 45/23 631/208/177 631/208/726 Article Humanities and Social Sciences multidisciplinary Science Science (multidisciplinary)
The cohesin complex structures the interphase genome of human cells by extruding loops and organizing topologically associating domains (TADs), yet how chromatin state regulates cohesin-chromatin interactions remains unclear. Here, we show that histone hyperacetylation induced by trichostatin A (TSA) selectively disrupts short-range intra-TAD interactions while largely preserving CTCF-anchored loops. These distinct responses define two functional cohesin populations: a TSA-sensitive pool associated with dynamic loop extrusion, and a TSA-resistant pool at CTCF sites maintained by topological entrapment. Using a semi-in vitro system with TEV-cleavable RAD21, we demonstrate that hyperacetylation increases the sensitivity of CTCF-anchored loops to cohesin ring cleavage, supporting a topological basis for their stability. We further identify a TSA-sensitive cohesin fraction at CTCF sites, suggesting transient, non-encircling intermediates. Together, our results reveal that cohesin exists in distinct biochemical states that differentially regulate chromatin loop stability and responsiveness to epigenomic perturbation. Here the authors show that histone hyperacetylation selectively disrupts dynamic chromatin loops while preserving CTCF-anchored loops, revealing distinct cohesin states that balance genome flexibility and structural stability.

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