Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin.

BACKGROUND The cohesin complex organizes the genome-forming dynamic chromatin loops that impact on all DNA-mediated processes. There are two different cohesin complexes in vertebrate somatic cells, carrying the STAG1 or STAG2 subunit, and two versions of the regulatory subunit PDS5, PDS5A and PDS5B....

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Autores: Cuadrado, Ana, Giménez-Llorente, Daniel, De Koninck, Magali, Ruiz-Torres, Miguel, Kojic, Aleksandar, Rodríguez-Corsino, Miriam, Losada, Ana
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17655
Acceso en línea:http://hdl.handle.net/20.500.12105/17655
Access Level:acceso abierto
Palabra clave:Chromosomal Proteins, Non-Histone
Cell Cycle Proteins
Mice
Animals
Chromatin
Genome
Carrier Proteins
Mammals
Cohesins
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spelling Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin.Cuadrado, AnaGiménez-Llorente, DanielDe Koninck, MagaliRuiz-Torres, MiguelKojic, AleksandarRodríguez-Corsino, MiriamLosada, AnaChromosomal Proteins, Non-HistoneCell Cycle ProteinsMiceAnimalsChromatinGenomeCarrier ProteinsMammalsCohesinsBACKGROUND The cohesin complex organizes the genome-forming dynamic chromatin loops that impact on all DNA-mediated processes. There are two different cohesin complexes in vertebrate somatic cells, carrying the STAG1 or STAG2 subunit, and two versions of the regulatory subunit PDS5, PDS5A and PDS5B. Mice deficient for any of the variant subunits are embryonic lethal, which indicates that they are not functionally redundant. However, their specific behavior at the molecular level is not fully understood. RESULTS The genome-wide distribution of cohesin provides important information with functional consequences. Here, we have characterized the distribution of cohesin subunits and regulators in mouse embryo fibroblasts (MEFs) either wild type or deficient for cohesin subunits and regulators by chromatin immunoprecipitation and deep sequencing. We identify non-CTCF cohesin-binding sites in addition to the commonly detected CTCF cohesin sites and show that cohesin-STAG2 is the preferred variant at these positions. Moreover, this complex has a more dynamic association with chromatin as judged by fluorescence recovery after photobleaching (FRAP), associates preferentially with WAPL and is more easily extracted from chromatin with salt than cohesin-STAG1. We observe that both PDS5A and PDS5B are exclusively located at cohesin-CTCF positions and that ablation of a single paralog has no noticeable consequences for cohesin distribution while double knocked out cells show decreased accumulation of cohesin at all its binding sites. With the exception of a fraction of cohesin positions in which we find binding of all regulators, including CTCF and WAPL, the presence of NIPBL and PDS5 is mutually exclusive, consistent with our immunoprecipitation analyses in mammalian cell extracts and previous results in yeast. CONCLUSION Our findings support the idea that non-CTCF cohesin-binding sites represent sites of cohesin loading or pausing and are preferentially occupied by the more dynamic cohesin-STAG2. PDS5 proteins redundantly contribute to arrest cohesin at CTCF sites, possibly by preventing binding of NIPBL, but are not essential for this arrest. These results add important insights towards understanding how cohesin regulates genome folding and the specific contributions of the different variants that coexist in the cell.BioMed Central (BMC)European Union (EU)Ministerio de Ciencia y Competitividad (España)20242024-02-0820222022-11-2420222022-11-24journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/17655reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/176552026-06-12T12:43:37Z
dc.title.none.fl_str_mv Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin.
title Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin.
spellingShingle Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin.
Cuadrado, Ana
Chromosomal Proteins, Non-Histone
Cell Cycle Proteins
Mice
Animals
Chromatin
Genome
Carrier Proteins
Mammals
Cohesins
title_short Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin.
title_full Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin.
title_fullStr Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin.
title_full_unstemmed Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin.
title_sort Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin.
dc.creator.none.fl_str_mv Cuadrado, Ana
Giménez-Llorente, Daniel
De Koninck, Magali
Ruiz-Torres, Miguel
Kojic, Aleksandar
Rodríguez-Corsino, Miriam
Losada, Ana
author Cuadrado, Ana
author_facet Cuadrado, Ana
Giménez-Llorente, Daniel
De Koninck, Magali
Ruiz-Torres, Miguel
Kojic, Aleksandar
Rodríguez-Corsino, Miriam
Losada, Ana
author_role author
author2 Giménez-Llorente, Daniel
De Koninck, Magali
Ruiz-Torres, Miguel
Kojic, Aleksandar
Rodríguez-Corsino, Miriam
Losada, Ana
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Union (EU)
Ministerio de Ciencia y Competitividad (España)
dc.subject.none.fl_str_mv Chromosomal Proteins, Non-Histone
Cell Cycle Proteins
Mice
Animals
Chromatin
Genome
Carrier Proteins
Mammals
Cohesins
topic Chromosomal Proteins, Non-Histone
Cell Cycle Proteins
Mice
Animals
Chromatin
Genome
Carrier Proteins
Mammals
Cohesins
description BACKGROUND The cohesin complex organizes the genome-forming dynamic chromatin loops that impact on all DNA-mediated processes. There are two different cohesin complexes in vertebrate somatic cells, carrying the STAG1 or STAG2 subunit, and two versions of the regulatory subunit PDS5, PDS5A and PDS5B. Mice deficient for any of the variant subunits are embryonic lethal, which indicates that they are not functionally redundant. However, their specific behavior at the molecular level is not fully understood. RESULTS The genome-wide distribution of cohesin provides important information with functional consequences. Here, we have characterized the distribution of cohesin subunits and regulators in mouse embryo fibroblasts (MEFs) either wild type or deficient for cohesin subunits and regulators by chromatin immunoprecipitation and deep sequencing. We identify non-CTCF cohesin-binding sites in addition to the commonly detected CTCF cohesin sites and show that cohesin-STAG2 is the preferred variant at these positions. Moreover, this complex has a more dynamic association with chromatin as judged by fluorescence recovery after photobleaching (FRAP), associates preferentially with WAPL and is more easily extracted from chromatin with salt than cohesin-STAG1. We observe that both PDS5A and PDS5B are exclusively located at cohesin-CTCF positions and that ablation of a single paralog has no noticeable consequences for cohesin distribution while double knocked out cells show decreased accumulation of cohesin at all its binding sites. With the exception of a fraction of cohesin positions in which we find binding of all regulators, including CTCF and WAPL, the presence of NIPBL and PDS5 is mutually exclusive, consistent with our immunoprecipitation analyses in mammalian cell extracts and previous results in yeast. CONCLUSION Our findings support the idea that non-CTCF cohesin-binding sites represent sites of cohesin loading or pausing and are preferentially occupied by the more dynamic cohesin-STAG2. PDS5 proteins redundantly contribute to arrest cohesin at CTCF sites, possibly by preventing binding of NIPBL, but are not essential for this arrest. These results add important insights towards understanding how cohesin regulates genome folding and the specific contributions of the different variants that coexist in the cell.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-11-24
2022
2022-11-24
2024
2024-02-08
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/17655
url http://hdl.handle.net/20.500.12105/17655
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central (BMC)
publisher.none.fl_str_mv BioMed Central (BMC)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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