Coordinated changes in gene expression, H1 variant distribution and genome 3D conformation in response to H1 depletion

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  • dc.contributor.author Serna Pujol, Núria
  • dc.contributor.author Salinas, Mònica
  • dc.contributor.author Mugianesi, Francesca
  • dc.contributor.author Le Dily, François
  • dc.contributor.author Marti-Renom, Marc A.
  • dc.contributor.author Jordan Vallès, Albert
  • dc.date.accessioned 2022-05-31T09:59:58Z
  • dc.date.available 2022-05-31T09:59:58Z
  • dc.date.issued 2022
  • dc.description.abstract Up to seven members of the histone H1 family may contribute to chromatin compaction and its regulation in human somatic cells. In breast cancer cells, knock-down of multiple H1 variants deregulates many genes, promotes the appearance of genome-wide accessibility sites and triggers an interferon response via activation of heterochromatic repeats. However, how these changes in the expression profile relate to the re-distribution of H1 variants as well as to genome conformational changes have not been yet studied. Here, we combined ChIP-seq of five endogenous H1 variants with Chromosome Conformation Capture analysis in wild-type and H1.2/H1.4 knock-down T47D cells. The results indicate that H1 variants coexist in the genome in two large groups depending on the local GC content and that their distribution is robust with respect to H1 depletion. Despite the small changes in H1 variants distribution, knock-down of H1 translated into more isolated but de-compacted chromatin structures at the scale of topologically associating domains (TADs). Such changes in TAD structure correlated with a coordinated gene expression response of their resident genes. This is the first report describing simultaneous profiling of five endogenous H1 variants and giving functional evidence of genome topology alterations upon H1 depletion in human cancer cells.
  • dc.description.sponsorship Funding: Spanish Ministry of Science and Innovation [BFU2017-82805-C2-1-P and PID2020-112783GB-C21 to A.J., BFU2017-85926-P and PID2020-115696RB-I00 to M.A.M.-R. (AEI/FEDER, EU)]; European Union's Seventh Framework Programme the ERC [609989 to M.A.M.-R., in part]; European Union's Horizon 2020 research and innovation programme [676556 to M.A.M.-R.]; Generalitat de Catalunya Suport Grups de Recerca [AGAUR 2017-SGR-597 to A.J. and 2017-SGR-468 to M.A.M.-R.]; C.R.G. acknowledges support from ‘Centro de Excelencia Severo Ochoa 2013–2017’; SEV-2012-0208; CERCA Programme/Generalitat de Catalunya as well as support of the Spanish Ministry of Science and Innovation through the Instituto de Salud Carlos III; Generalitat de Catalunya through Departament de Salut and Departament d’Empresa i Coneixement; Spanish Ministry of Science and Innovation with funds from the European Regional Development Fund (ERDF) corresponding to the 2014–2020 Smart Growth Operating Program. Funding for open access charge: Spanish Ministry of Science and Innovation
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Serna-Pujol N, Salinas-Pena M, Mugianesi F, Le Dily F, Marti-Renom MA, Jordan A. Coordinated changes in gene expression, H1 variant distribution and genome 3D conformation in response to H1 depletion. Nucleic Acids Res. 2022 Apr 22;50(7):3892-3910. DOI:10.1093/nar/gkac226
  • dc.identifier.doi http://dx.doi.org/10.1093/nar/gkac226
  • dc.identifier.issn 0305-1048
  • dc.identifier.uri http://hdl.handle.net/10230/53329
  • dc.language.iso eng
  • dc.publisher Oxford University Press
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/676556
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-85926-P
  • dc.rights © Núria Serna-Pujol et al. 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Genètica
  • dc.subject.other Genòmica
  • dc.subject.other Càncer
  • dc.title Coordinated changes in gene expression, H1 variant distribution and genome 3D conformation in response to H1 depletion
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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