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 Barba, 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.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.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.doi http://dx.doi.org/10.7554/eLife.66034
• dc.identifier.issn 2050-084X
• dc.identifier.uri http://hdl.handle.net/10230/52830
• dc.language.iso eng
• dc.publisher eLife Sciences Publications
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
• dc.relation.projectID https://creativecommons.org/licenses/by/4.0/
• 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.rights.accessRights info:eu-repo/semantics/openAccess
• 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.type.version info:eu-repo/semantics/publishedVersion