Distinct structural transitions of chromatin topological domains correlate with coordinated hormone-induced gene regulation

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• dc.contributor.author Le Dily, François
• dc.contributor.author Baù, Davide
• dc.contributor.author Pohl, Andy, 1979-
• dc.contributor.author Vicent, Guillermo Pablo
• dc.contributor.author Serra, François
• dc.contributor.author Soronellas, Daniel
• dc.contributor.author Castellano, Giancarlo
• dc.contributor.author Wright, Roni H.G.
• dc.contributor.author Ballare, Cecilia Julia
• dc.contributor.author Filion, Guillaume
• dc.contributor.author Marti-Renom, Marc A.
• dc.contributor.author Beato, Miguel
• dc.date.accessioned 2024-02-20T07:17:36Z
• dc.date.available 2024-02-20T07:17:36Z
• dc.date.issued 2014
• dc.description Includes supplementary materials for the online appendix.
• dc.description.abstract The human genome is segmented into topologically associating domains (TADs), but the role of this conserved organization during transient changes in gene expression is not known. Here we describe the distribution of progestin-induced chromatin modifications and changes in transcriptional activity over TADs in T47D breast cancer cells. Using ChIP-seq (chromatin immunoprecipitation combined with high-throughput sequencing), Hi-C (chromosome capture followed by high-throughput sequencing), and three-dimensional (3D) modeling techniques, we found that the borders of the ∼ 2000 TADs in these cells are largely maintained after hormone treatment and that up to 20% of the TADs could be considered as discrete regulatory units where the majority of the genes are either transcriptionally activated or repressed in a coordinated fashion. The epigenetic signatures of the TADs are homogeneously modified by hormones in correlation with the transcriptional changes. Hormone-induced changes in gene activity and chromatin remodeling are accompanied by differential structural changes for activated and repressed TADs, as reflected by specific and opposite changes in the strength of intra-TAD interactions within responsive TADs. Indeed, 3D modeling of the Hi-C data suggested that the structure of TADs was modified upon treatment. The differential responses of TADs to progestins and estrogens suggest that TADs could function as "regulons" to enable spatially proximal genes to be coordinately transcribed in response to hormones.
• dc.description.sponsorship We acknowledge financial support from the Spanish Ministry of Economy and Competitiveness (MINECO) (BFU2010-19310/BMC) and the Human Frontiers Science Program (RGP0044/2011) (to M.A.M.-R.). This work was also supported by grants from the Spanish government (BMC 2003-02902, BMC 2010-15313, and CSD2006-00049) and the Catalan government (Agència de Gestió d’Ajuts Universitaris i de Recerca [AGAUR]) (to M.B.). We acknowledge support of the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017,’ SEV-2012-0208. F.L.D., G.F., M.A.M-R., and M.B. designed the studies. F.L.D. performed Hi-C, FISH, and RNA-seq experiments. G.V., R.H.G.W, and C.B. performed ChIP-seq experiments. F.L.D. carried out the data analysis with contributions from A.P., D.S., G.C., and G.F., and F.S., D.B., and M.A.M-R. carried out the 3D modelling and analysis. F.S. and G.F. designed the TAD boundary algorithm. All of the authors discussed the results, and F.L.D., M.A.M-R., and M.B. wrote the manuscript.
• dc.format.mimetype application/pdf
• dc.identifier.citation Le F, Baù D, Pohl A, Vicent GP, Serra F, Soronellas D, et al. Distinct structural transitions of chromatin topological domains correlate with coordinated hormone-induced gene regulation. Genes Dev. 2014 Oct 1;28(19):2151-62. DOI: 10.1101/gad.241422.114
• dc.identifier.doi http://dx.doi.org/10.1101/gad.241422.114
• dc.identifier.issn 0890-9369
• dc.identifier.uri http://hdl.handle.net/10230/59157
• dc.language.iso eng
• dc.publisher Cold Spring Harbor Laboratory Press (CSHL Press)
• dc.relation.ispartof Genes & Development. 2014 Oct 1;28(19):2151-62
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2010-19310
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/CSD2006-00049
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SEV2012-0208
• dc.rights © 2014 Le Dily et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.keyword Hi-C
• dc.subject.keyword TADs
• dc.subject.keyword Epigenetic landscape
• dc.subject.keyword Gene expression
• dc.subject.keyword Progesterone receptor
• dc.subject.keyword Three-dimensional structure of the genome
• dc.subject.keyword Transcriptional regulation
• dc.title Distinct structural transitions of chromatin topological domains correlate with coordinated hormone-induced gene regulation
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion