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Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells

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dc.contributor.author La Greca, Alejandro
dc.contributor.author Bellora Pereyra, Nicolás
dc.contributor.author Le Dily, François
dc.contributor.author Jara, Rodrigo
dc.contributor.author Nacht, A. Silvina
dc.contributor.author Quilez Oliete, Javier
dc.contributor.author Villanueva Cañas, José Luis, 1984-
dc.contributor.author Vidal, Enric
dc.contributor.author Merino, Gabriela
dc.contributor.author Fresno, Cristóbal
dc.contributor.author Reischle, Inti Tarifa
dc.contributor.author Vallejo, Griselda
dc.contributor.author Vicent, Guillermo Pablo
dc.contributor.author Fernández, Elmer
dc.contributor.author Beato, Miguel
dc.contributor.author Saragüeta, Patricia
dc.date.accessioned 2022-04-05T10:07:39Z
dc.date.available 2022-04-05T10:07:39Z
dc.date.issued 2022
dc.identifier.citation La Greca A, Bellora N, Le Dily F, Jara R, Nacht AS, Quilez Oliete J et al. Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells. Elife. 2022 Jan 12;11:e66034. DOI: 10.7554/eLife.66034
dc.identifier.issn 2050-084X
dc.identifier.uri http://hdl.handle.net/10230/52830
dc.description.abstract Estrogen (E2) and Progesterone (Pg), via their specific receptors (ERalpha and PR), are major determinants in the development and progression of endometrial carcinomas, However, their precise mechanism of action and the role of other transcription factors involved are not entirely clear. Using Ishikawa endometrial cancer cells, we report that E2 treatment exposes a set of progestin-dependent PR binding sites which include both E2 and progestin target genes. ChIP-seq results from hormone-treated cells revealed a non-random distribution of PAX2 binding in the vicinity of these estrogen-promoted PR sites. Altered expression of hormone regulated genes in PAX2 knockdown cells suggests a role for PAX2 in fine-tuning ERalpha and PR interplay in transcriptional regulation. Analysis of long-range interactions by Hi-C coupled with ATAC-seq data showed that these regions, that we call 'progestin control regions' (PgCRs), exhibited an open chromatin state even before hormone exposure and were non-randomly associated with regulated genes. Nearly 20% of genes potentially influenced by PgCRs were found to be altered during progression of endometrial cancer. Our findings suggest that endometrial response to progestins in differentiated endometrial tumor cells results in part from binding of PR together with PAX2 to accessible chromatin regions. What maintains these regions open remains to be studied.
dc.description.sponsorship Funding: Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 2015-682), Fondo para la Investigación Científica y Tecnológica (PICT 2015-3426) and H2020 European Research Council (FP7/2007-2013 grant agreement 609989)
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher eLife Sciences Publications
dc.rights © 2022, La Greca et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited
dc.subject.other Genètica
dc.subject.other Càncer
dc.subject.other Estrògens
dc.subject.other Progesterona
dc.title Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.7554/eLife.66034
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
dc.relation.projectID https://creativecommons.org/licenses/by/4.0/
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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