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| Status |
Public on Mar 14, 2022 |
| Title |
The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism (Hi-C) |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Cohesin structures the genome through the formation of chromatin loops and by holding together the sister chromatids from S-phase until mitosis. The acetylation of cohesin’s SMC3 subunit is a dynamic process that involves the acetyltransferase ESCO1 and deacetylase HDAC8. Here we show that this cohesin acetylation cycle controls the 3D genome. ESCO1 restricts the length of chromatin loops and architectural stripes, while HDAC8 rather promotes the extension of such loops and stripes. This role in controlling loop length turns out to be distinct from the canonical role of cohesin acetylation that protects against WAPL-mediated DNA release. We reveal that acetylation rather controls cohesin’s interaction with PDS5A to restrict chromatin loop length. Our data supports a model in which this PDS5A-bound state acts as a brake that enables the pausing and restart of loop enlargement. The cohesin acetylation cycle hereby provides punctuation in the process of genome folding.
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| Overall design |
Hi-C was performed in G1 isolated cells from the following genotypes: Wild Type, ∆ESCO1, ∆HDAC8, ∆ESCO1/∆HDAC8, ∆WAPL, ∆WAPL/∆ESCO1, ∆PDS5A, ∆PDS5B and ∆PDS5A/∆HDAC8 cells. Hi-C replicate experiments were performed in all genotypes. Asynchronous Hi-C analysis was performed in Wild Type cells and ∆HDAC8 cells.
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| Contributor(s) |
van Ruiten MS, Cacciatore ÁS, van Gent D, Fauster A, Willems L, Haarhuis JH, Brummelkamp TR, de Wit E, Rowland BD |
| Citation(s) |
35710836 |
| |
| Submission date |
May 14, 2020 |
| Last update date |
Jun 21, 2022 |
| Contact name |
Angela Sedeno Cacciatore |
| E-mail(s) |
[email protected], [email protected]
|
| Organization name |
Netherlands Cancer Institute
|
| Department |
Gene regulation
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| Lab |
Rowland lab
|
| Street address |
Plesmanlaan 121
|
| City |
Amsterdam |
| State/province |
Noord-Holland |
| ZIP/Postal code |
1066 CX |
| Country |
Netherlands |
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| Platforms (2) |
| GPL21697 |
NextSeq 550 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (23)
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| This SubSeries is part of SuperSeries: |
| GSE174628 |
The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism |
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| Relations |
| BioProject |
PRJNA632826 |
| SRA |
SRP261602 |
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