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The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism

Cohesin structures the genome through the formation of chromatin loops and by holding together the sister chromatids. 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 contr...

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Autores principales: van Ruiten, Marjon S., van Gent, Démi, Sedeño Cacciatore, Ángela, Fauster, Astrid, Willems, Laureen, Hekkelman, Maarten L., Hoekman, Liesbeth, Altelaar, Maarten, Haarhuis, Judith H. I., Brummelkamp, Thijn R., de Wit, Elzo, Rowland, Benjamin D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205776/
https://www.ncbi.nlm.nih.gov/pubmed/35710836
http://dx.doi.org/10.1038/s41594-022-00773-z
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author van Ruiten, Marjon S.
van Gent, Démi
Sedeño Cacciatore, Ángela
Fauster, Astrid
Willems, Laureen
Hekkelman, Maarten L.
Hoekman, Liesbeth
Altelaar, Maarten
Haarhuis, Judith H. I.
Brummelkamp, Thijn R.
de Wit, Elzo
Rowland, Benjamin D.
author_facet van Ruiten, Marjon S.
van Gent, Démi
Sedeño Cacciatore, Ángela
Fauster, Astrid
Willems, Laureen
Hekkelman, Maarten L.
Hoekman, Liesbeth
Altelaar, Maarten
Haarhuis, Judith H. I.
Brummelkamp, Thijn R.
de Wit, Elzo
Rowland, Benjamin D.
author_sort van Ruiten, Marjon S.
collection PubMed
description Cohesin structures the genome through the formation of chromatin loops and by holding together the sister chromatids. 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 three-dimensional genome in human cells. ESCO1 restricts the length of chromatin loops, and of architectural stripes emanating from CTCF sites. HDAC8 conversely 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 controls the interaction of cohesin with PDS5A to restrict chromatin loop length. Our data support 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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spelling pubmed-92057762022-06-19 The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism van Ruiten, Marjon S. van Gent, Démi Sedeño Cacciatore, Ángela Fauster, Astrid Willems, Laureen Hekkelman, Maarten L. Hoekman, Liesbeth Altelaar, Maarten Haarhuis, Judith H. I. Brummelkamp, Thijn R. de Wit, Elzo Rowland, Benjamin D. Nat Struct Mol Biol Article Cohesin structures the genome through the formation of chromatin loops and by holding together the sister chromatids. 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 three-dimensional genome in human cells. ESCO1 restricts the length of chromatin loops, and of architectural stripes emanating from CTCF sites. HDAC8 conversely 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 controls the interaction of cohesin with PDS5A to restrict chromatin loop length. Our data support 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. Nature Publishing Group US 2022-06-16 2022 /pmc/articles/PMC9205776/ /pubmed/35710836 http://dx.doi.org/10.1038/s41594-022-00773-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
van Ruiten, Marjon S.
van Gent, Démi
Sedeño Cacciatore, Ángela
Fauster, Astrid
Willems, Laureen
Hekkelman, Maarten L.
Hoekman, Liesbeth
Altelaar, Maarten
Haarhuis, Judith H. I.
Brummelkamp, Thijn R.
de Wit, Elzo
Rowland, Benjamin D.
The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism
title The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism
title_full The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism
title_fullStr The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism
title_full_unstemmed The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism
title_short The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism
title_sort cohesin acetylation cycle controls chromatin loop length through a pds5a brake mechanism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205776/
https://www.ncbi.nlm.nih.gov/pubmed/35710836
http://dx.doi.org/10.1038/s41594-022-00773-z
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