Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation

A hallmark of chromosome organization is the partition into transcriptionally active A and repressed B compartments, and into topologically associating domains (TADs). Both structures were regarded to be absent from the inactive mouse X chromosome, but to be re-established with transcriptional react...

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Autores: Bauer, Moritz, 1987-, Vidal, Enrique, Zorita, Eduard, Üresin, Nil, Pinter, Stefan F., Filion, Guillaume, Payer, Bernhard
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/49045
Acceso en línea:http://hdl.handle.net/10230/49045
http://dx.doi.org/10.1038/s41467-021-23610-1
Access Level:acceso abierto
Palabra clave:Chromatin structure
Dosage compensation
Epigenetics
Epigenomics
Reprogramming
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spelling Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivationBauer, Moritz, 1987-Vidal, EnriqueZorita, EduardÜresin, NilPinter, Stefan F.Filion, GuillaumePayer, BernhardChromatin structureDosage compensationEpigeneticsEpigenomicsReprogrammingA hallmark of chromosome organization is the partition into transcriptionally active A and repressed B compartments, and into topologically associating domains (TADs). Both structures were regarded to be absent from the inactive mouse X chromosome, but to be re-established with transcriptional reactivation and chromatin opening during X-reactivation. Here, we combine a tailor-made mouse iPSC reprogramming system and high-resolution Hi-C to produce a time course combining gene reactivation, chromatin opening and chromosome topology during X-reactivation. Contrary to previous observations, we observe A/B-like compartments on the inactive X harbouring multiple subcompartments. While partial X-reactivation initiates within a compartment rich in X-inactivation escapees, it then occurs rapidly along the chromosome, concomitant with downregulation of Xist. Importantly, we find that TAD formation precedes transcription and initiates from Xist-poor compartments. Here, we show that TAD formation and transcriptional reactivation are causally independent during X-reactivation while establishing Xist as a common denominator.This work was supported by the European Research Council under the 7th Framework Programme FP7/2007-2013 (ERC Synergy Grant 4D-Genome, grant agreement 609989 to G.J.F.), by the Spanish Ministry of Science, Innovation and Universities (BFU2014-55275-P, BFU2017-88407-P to B.P. and PGC2018-099807-B-I00 to G.J.F.), the Agencia Estatal de Investigación (AEI) (EUR2019-103817 to B.P.), the AXA Research Fund (to B.P.) and the Agencia de Gestio d’Ajuts Universitaris i de Recerca (AGAUR, 2017 SGR 346 to B.P.) and by the NIH grant R35GM124926 to S.F.P. We would like to thank the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership and to the “Centro de Excelencia Severo Ochoa”. We also acknowledge support of the CERCA Programme of the Generalitat de Catalunya. M.B. was supported by a La Caixa International PhD Fellowship.Nature Research202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/49045http://dx.doi.org/10.1038/s41467-021-23610-1reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésNat Commun. 2021;12(1):3499info:eu-repo/grantAgreement/EC/FP7/609989info:eu-repo/grantAgreement/ES/1PE/BFU2014-55275-Pinfo:eu-repo/grantAgreement/ES/2PE/BFU2017-88407-Pinfo:eu-repo/grantAgreement/ES/2PE/PGC2018-099807-B-I00© The Author(s) 2021. 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/.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/490452026-06-12T07:21:37Z
dc.title.none.fl_str_mv Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation
title Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation
spellingShingle Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation
Bauer, Moritz, 1987-
Chromatin structure
Dosage compensation
Epigenetics
Epigenomics
Reprogramming
title_short Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation
title_full Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation
title_fullStr Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation
title_full_unstemmed Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation
title_sort Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation
dc.creator.none.fl_str_mv Bauer, Moritz, 1987-
Vidal, Enrique
Zorita, Eduard
Üresin, Nil
Pinter, Stefan F.
Filion, Guillaume
Payer, Bernhard
author Bauer, Moritz, 1987-
author_facet Bauer, Moritz, 1987-
Vidal, Enrique
Zorita, Eduard
Üresin, Nil
Pinter, Stefan F.
Filion, Guillaume
Payer, Bernhard
author_role author
author2 Vidal, Enrique
Zorita, Eduard
Üresin, Nil
Pinter, Stefan F.
Filion, Guillaume
Payer, Bernhard
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Chromatin structure
Dosage compensation
Epigenetics
Epigenomics
Reprogramming
topic Chromatin structure
Dosage compensation
Epigenetics
Epigenomics
Reprogramming
description A hallmark of chromosome organization is the partition into transcriptionally active A and repressed B compartments, and into topologically associating domains (TADs). Both structures were regarded to be absent from the inactive mouse X chromosome, but to be re-established with transcriptional reactivation and chromatin opening during X-reactivation. Here, we combine a tailor-made mouse iPSC reprogramming system and high-resolution Hi-C to produce a time course combining gene reactivation, chromatin opening and chromosome topology during X-reactivation. Contrary to previous observations, we observe A/B-like compartments on the inactive X harbouring multiple subcompartments. While partial X-reactivation initiates within a compartment rich in X-inactivation escapees, it then occurs rapidly along the chromosome, concomitant with downregulation of Xist. Importantly, we find that TAD formation precedes transcription and initiates from Xist-poor compartments. Here, we show that TAD formation and transcriptional reactivation are causally independent during X-reactivation while establishing Xist as a common denominator.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/49045
http://dx.doi.org/10.1038/s41467-021-23610-1
url http://hdl.handle.net/10230/49045
http://dx.doi.org/10.1038/s41467-021-23610-1
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nat Commun. 2021;12(1):3499
info:eu-repo/grantAgreement/EC/FP7/609989
info:eu-repo/grantAgreement/ES/1PE/BFU2014-55275-P
info:eu-repo/grantAgreement/ES/2PE/BFU2017-88407-P
info:eu-repo/grantAgreement/ES/2PE/PGC2018-099807-B-I00
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
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repository.mail.fl_str_mv
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