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Published on: March 31, 2019
Histone Acetylation Differentially Modulates CTCF-CTCF Loops and Intra-TAD Interactions
Rebecca G Smith1,2,3,4, Yu Fu5, Kathleen L Schiela1,2,3,4
1Cancer Epigenetics Institute, Fox Chase Cancer Center, Philadelphia, PA, USA.
Nature Communications
|July 20, 2026
Summary
Histone hyperacetylation disrupts short-range chromatin loops but preserves CTCF-anchored ones, revealing two functional cohesin populations with distinct biochemical states and regulatory roles in genome organization.
Area of Science:
- Genomics
- Epigenetics
- Molecular Biology
Background:
- The cohesin complex organizes the human genome by forming loops and topologically associating domains (TADs).
- The influence of chromatin state on cohesin-chromatin interactions is not fully understood.
Purpose of the Study:
- To investigate how histone hyperacetylation affects cohesin-chromatin interactions and genome structure.
- To differentiate functional cohesin populations based on their response to epigenomic perturbation.
Main Methods:
- Induction of histone hyperacetylation using trichostatin A (TSA).
- Analysis of cohesin-chromatin interactions and loop stability.
- Utilizing a semi-in vitro system with TEV-cleavable RAD21.
Main Results:
- Histone hyperacetylation selectively disrupts short-range intra-TAD interactions, sparing CTCF-anchored loops.
- Two cohesin populations were identified: TSA-sensitive (dynamic loop extrusion) and TSA-resistant (CTCF-site topological entrapment).
- Hyperacetylation increases the sensitivity of CTCF-anchored loops to cohesin ring cleavage, indicating topological stability.
Conclusions:
- Cohesin exists in distinct biochemical states that differentially control chromatin loop stability.
- Epigenomic perturbations, like histone hyperacetylation, reveal functional heterogeneity within cohesin populations.
- These findings provide insights into the dynamic regulation of genome architecture by cohesin.
Related Concept Videos
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:32Histone Modification
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Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
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02:25Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
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Writers
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These groups modify specific amino acids in a protein.
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02:30Histone Variants at the Centromere
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02:38Heterochromatin
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Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
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