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A set of accessible enhancers enables the initial response of breast cancer cells to physiological progestin concentrations

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dc.contributor.author Zaurín Quer, Roser
dc.contributor.author Ferrari, Roberto
dc.contributor.author Nacht, A. Silvina
dc.contributor.author Carbonell-Caballero, Jose
dc.contributor.author Le Dily, François
dc.contributor.author Font Mateu, Jofre, 1977-
dc.contributor.author De Llobet, Lara Isabel
dc.contributor.author Vidal Ocabo, Enrique
dc.contributor.author Lioutas, Antonio, 1980-
dc.contributor.author Beato, Miguel
dc.contributor.author Vincent, Guillermo P.
dc.date.accessioned 2022-04-01T09:19:33Z
dc.date.available 2022-04-01T09:19:33Z
dc.date.issued 2021
dc.identifier.citation Zaurin R, Ferrari R, Nacht AS, Carbonell J, Le Dily F, Font-Mateu J et al. A set of accessible enhancers enables the initial response of breast cancer cells to physiological progestin concentrations. Nucleic Acids Res. 2021 Dec 16;49(22):12716-31. DOI: 10.1093/nar/gkab1125
dc.identifier.issn 0305-1048
dc.identifier.uri http://hdl.handle.net/10230/52813
dc.description.abstract Here, we report that in T47D breast cancer cells 50 pM progestin is sufficient to activate cell cycle entry and the progesterone gene expression program. At this concentration, equivalent to the progesterone blood levels found around the menopause, progesterone receptor (PR) binds only to 2800 genomic sites, which are accessible to ATAC cleavage prior to hormone exposure. These highly accessible sites (HAs) are surrounded by well-organized nucleosomes and exhibit breast enhancer features, including estrogen receptor alpha (ERα), higher FOXA1 and BRD4 (bromodomain containing 4) occupancy. Although HAs are enriched in RAD21 and CTCF, PR binding is the driving force for the most robust interactions with hormone-regulated genes. HAs show higher frequency of 3D contacts among themselves than with other PR binding sites, indicating colocalization in similar compartments. Gene regulation via HAs is independent of classical coregulators and ATP-activated remodelers, relying mainly on MAP kinase activation that enables PR nuclear engagement. HAs are also preferentially occupied by PR and ERα in breast cancer xenografts derived from MCF-7 cells as well as from patients, indicating their potential usefulness as targets for therapeutic intervention.
dc.description.sponsorship Funding: Ministerio de Ciencia e Innovación [PID2019-105173RB-I00 and PID2019-110384GB-C21]; Spanish Ministry of Economy and Competitiveness [SAF2016-75006-P and G62426937]; Consejo Superior de Investigaciones Científicas [201820I131]; Centro de Excelencia Severo Ochoa [SEV-2012-2018]; European Research Council [609989]. Funding for open access charge: Ministerio de Ciencia e Innovación
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Oxford University Press
dc.rights © Roser Zaurin et al. 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-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.subject.other Genètica
dc.subject.other Mama -- Càncer
dc.title A set of accessible enhancers enables the initial response of breast cancer cells to physiological progestin concentrations
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1093/nar/gkab1125
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-75006-P
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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