Hormone-control regions mediate steroid receptor-dependent genome organization

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  • dc.contributor.author Le Dily, François
  • dc.contributor.author Vidal, Enrique
  • dc.contributor.author Cuartero, Yasmina
  • dc.contributor.author Quilez Oliete, Javier
  • dc.contributor.author Nacht, A. Silvina
  • dc.contributor.author Vicent, Guillermo Pablo
  • dc.contributor.author Carbonell-Caballero, Jose
  • dc.contributor.author Sharma, Priyanka
  • dc.contributor.author Villanueva Cañas, José Luis, 1984-
  • dc.contributor.author Ferrari, Roberto
  • dc.contributor.author De Llobet, Lara Isabel
  • dc.contributor.author Verde, Gaetano
  • dc.contributor.author Wright, Roni H.G.
  • dc.contributor.author Beato, Miguel
  • dc.date.accessioned 2019-07-04T07:00:53Z
  • dc.date.available 2019-07-04T07:00:53Z
  • dc.date.issued 2019
  • dc.description.abstract In breast cancer cells, some topologically associating domains (TADs) behave as hormonal gene regulation units, within which gene transcription is coordinately regulated in response to steroid hormones. Here we further describe that responsive TADs contain 20- to 100-kb-long clusters of intermingled estrogen receptor (ESR1) and progesterone receptor (PGR) binding sites, hereafter called hormone-control regions (HCRs). In T47D cells, we identified more than 200 HCRs, which are frequently bound by unliganded ESR1 and PGR. These HCRs establish steady long-distance inter-TAD interactions between them and organize characteristic looping structures with promoters in their TADs even in the absence of hormones in ESR1+-PGR+ cells. This organization is dependent on the expression of the receptors and is further dynamically modulated in response to steroid hormones. HCRs function as platforms that integrate different signals, resulting in some cases in opposite transcriptional responses to estrogens or progestins. Altogether, these results suggest that steroid hormone receptors act not only as hormone-regulated sequence-specific transcription factors but also as local and global genome organizers.
  • dc.description.sponsorship We received funding from the European Research Council under the European Union's Seventh Framework Program (FP7/2007–2013)/ERC Synergy grant agreement 609989 (4DGenome). The content of this manuscript reflects only the author's views and the Union is not liable for any use that may be made of the information contained therein. We acknowledge support of the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013–2017’ and Plan Nacional (SAF2016-75006-P), as well as support of the CERCA Programme/Generalitat de Catalunya.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Le Dily F, Vidal E, Cuartero Y, Quilez J, Nacht AS, Vicent GP, Carbonell-Caballero J, Sharma P, Villanueva-Cañas JL, Ferrari R, De Llobet LI, Verde G, Wright RHG, Beato M. Hormone-control regions mediate steroid receptor-dependent genome organization. Genome Res. 2019; 29(1):29-39. DOI 10.1101/gr.243824.118
  • dc.identifier.doi http://dx.doi.org/10.1101/gr.243824.118
  • dc.identifier.issn 1088-9051
  • dc.identifier.uri http://hdl.handle.net/10230/41930
  • dc.language.iso eng
  • dc.publisher Cold Spring Harbor Laboratory Press (CSHL Press)
  • dc.relation.ispartof Genome Res. 2019; 29(1):29-39
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-75006-P
  • dc.rights © 2019 Le Dily et al. Published originally by Cold Spring Harbor Laboratory Press at http://dx.doi.org/10.1101/gr.243824.118. Beginning six months from the full-issue publication date, articles are distributed under the Creative Commons Attribution-Non-Commercial 4.0 International License (CC-BY-NC), as described at http://creativecommons.org/licenses/by-nc/4.0/. This license permits non-commercial use, including reproduction, adaptation, and distribution of the article provided the original author and source are credited.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.title Hormone-control regions mediate steroid receptor-dependent genome organization
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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