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Brca2, Pds5 and Wapl differentially control cohesin chromosome association and function
The cohesin complex topologically encircles chromosomes and mediates sister chromatid cohesion to ensure accurate chromosome segregation upon cell division. Cohesin also participates in DNA repair and gene transcription. The Nipped-B–Mau2 protein complex loads cohesin onto chromosomes and the Pds5—W...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831647/ https://www.ncbi.nlm.nih.gov/pubmed/29447171 http://dx.doi.org/10.1371/journal.pgen.1007225 |
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author | Misulovin, Ziva Pherson, Michelle Gause, Maria Dorsett, Dale |
author_facet | Misulovin, Ziva Pherson, Michelle Gause, Maria Dorsett, Dale |
author_sort | Misulovin, Ziva |
collection | PubMed |
description | The cohesin complex topologically encircles chromosomes and mediates sister chromatid cohesion to ensure accurate chromosome segregation upon cell division. Cohesin also participates in DNA repair and gene transcription. The Nipped-B–Mau2 protein complex loads cohesin onto chromosomes and the Pds5—Wapl complex removes cohesin. Pds5 is also essential for sister chromatid cohesion, indicating that it has functions beyond cohesin removal. The Brca2 DNA repair protein interacts with Pds5, but the roles of this complex beyond DNA repair are unknown. Here we show that Brca2 opposes Pds5 function in sister chromatid cohesion by assaying precocious sister chromatid separation in metaphase spreads of cultured cells depleted for these proteins. By genome-wide chromatin immunoprecipitation we find that Pds5 facilitates SA cohesin subunit association with DNA replication origins and that Brca2 inhibits SA binding, mirroring their effects on sister chromatid cohesion. Cohesin binding is maximal at replication origins and extends outward to occupy active genes and regulatory sequences. Pds5 and Wapl, but not Brca2, limit the distance that cohesin extends from origins, thereby determining which active genes, enhancers and silencers bind cohesin. Using RNA-seq we find that Brca2, Pds5 and Wapl influence the expression of most genes sensitive to Nipped-B and cohesin, largely in the same direction. These findings demonstrate that Brca2 regulates sister chromatid cohesion and gene expression in addition to its canonical role in DNA repair and expand the known functions of accessory proteins in cohesin’s diverse functions. |
format | Online Article Text |
id | pubmed-5831647 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58316472018-03-15 Brca2, Pds5 and Wapl differentially control cohesin chromosome association and function Misulovin, Ziva Pherson, Michelle Gause, Maria Dorsett, Dale PLoS Genet Research Article The cohesin complex topologically encircles chromosomes and mediates sister chromatid cohesion to ensure accurate chromosome segregation upon cell division. Cohesin also participates in DNA repair and gene transcription. The Nipped-B–Mau2 protein complex loads cohesin onto chromosomes and the Pds5—Wapl complex removes cohesin. Pds5 is also essential for sister chromatid cohesion, indicating that it has functions beyond cohesin removal. The Brca2 DNA repair protein interacts with Pds5, but the roles of this complex beyond DNA repair are unknown. Here we show that Brca2 opposes Pds5 function in sister chromatid cohesion by assaying precocious sister chromatid separation in metaphase spreads of cultured cells depleted for these proteins. By genome-wide chromatin immunoprecipitation we find that Pds5 facilitates SA cohesin subunit association with DNA replication origins and that Brca2 inhibits SA binding, mirroring their effects on sister chromatid cohesion. Cohesin binding is maximal at replication origins and extends outward to occupy active genes and regulatory sequences. Pds5 and Wapl, but not Brca2, limit the distance that cohesin extends from origins, thereby determining which active genes, enhancers and silencers bind cohesin. Using RNA-seq we find that Brca2, Pds5 and Wapl influence the expression of most genes sensitive to Nipped-B and cohesin, largely in the same direction. These findings demonstrate that Brca2 regulates sister chromatid cohesion and gene expression in addition to its canonical role in DNA repair and expand the known functions of accessory proteins in cohesin’s diverse functions. Public Library of Science 2018-02-15 /pmc/articles/PMC5831647/ /pubmed/29447171 http://dx.doi.org/10.1371/journal.pgen.1007225 Text en © 2018 Misulovin et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Misulovin, Ziva Pherson, Michelle Gause, Maria Dorsett, Dale Brca2, Pds5 and Wapl differentially control cohesin chromosome association and function |
title | Brca2, Pds5 and Wapl differentially control cohesin chromosome association and function |
title_full | Brca2, Pds5 and Wapl differentially control cohesin chromosome association and function |
title_fullStr | Brca2, Pds5 and Wapl differentially control cohesin chromosome association and function |
title_full_unstemmed | Brca2, Pds5 and Wapl differentially control cohesin chromosome association and function |
title_short | Brca2, Pds5 and Wapl differentially control cohesin chromosome association and function |
title_sort | brca2, pds5 and wapl differentially control cohesin chromosome association and function |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831647/ https://www.ncbi.nlm.nih.gov/pubmed/29447171 http://dx.doi.org/10.1371/journal.pgen.1007225 |
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