dc.contributor.author |
Nacht, A. Silvina |
dc.contributor.author |
Ferrari, Roberto |
dc.contributor.author |
Zaurín Quer, Roser |
dc.contributor.author |
Scabia, Valentina |
dc.contributor.author |
Carbonell-Caballero, Jose |
dc.contributor.author |
Le Dily, François |
dc.contributor.author |
Quilez Oliete, Javier |
dc.contributor.author |
Leopoldi, Alexandra |
dc.contributor.author |
Brisken, Cathrin |
dc.contributor.author |
Beato, Miguel |
dc.contributor.author |
Vicent, Guillermo Pablo |
dc.date.accessioned |
2020-02-10T12:00:46Z |
dc.date.available |
2020-02-10T12:00:46Z |
dc.date.issued |
2019 |
dc.identifier.citation |
Nacht, A S, Ferrari R, Zaurin R, Sacabia V, Carbonell-Caballero J, Le Dily F et al. C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells. EMBO J. 2019;38(18):e101426. DOI: 10.15252/embj.2018101426 |
dc.identifier.issn |
0261-4189 |
dc.identifier.uri |
http://hdl.handle.net/10230/43543 |
dc.description.abstract |
Steroid hormones are key gene regulators in breast cancer cells. While estrogens stimulate cell proliferation, progestins activate a single cell cycle followed by proliferation arrest. Here, we use biochemical and genome-wide approaches to show that progestins achieve this effect via a functional crosstalk with C/EBPα. Using ChIP-seq, we identify around 1,000 sites where C/EBPα binding precedes and helps binding of progesterone receptor (PR) in response to hormone. These regions exhibit epigenetic marks of active enhancers, and C/EBPα maintains an open chromatin conformation that facilitates loading of ligand-activated PR. Prior to hormone exposure, C/EBPα favors promoter-enhancer contacts that assure hormonal regulation of key genes involved in cell proliferation by facilitating binding of RAD21, YY1, and the Mediator complex. Knockdown of C/EBPα disrupts enhancer-promoter contacts and decreases the presence of these architectural proteins, highlighting its key role in 3D chromatin looping. Thus, C/EBPα fulfills a previously unknown function as a potential growth modulator in hormone-dependent breast cancer. |
dc.description.sponsorship |
The experimental work was supported by grants from the Departament d’Innovació, Universitat i Empresa (DIUiE), and the Spanish Ministry of Economy and Competitiveness (SAF2016-75006P), “Centro de Excelencia Severo Ochoa 2013-2017”, SEV-2012-0208 and ERC Synergy Grant “4DGenome” nr: 609989 |
dc.format.mimetype |
application/pdf |
dc.language.iso |
eng |
dc.publisher |
EMBO Press |
dc.relation.ispartof |
EMBO Journal. 2019;38(18):e101426 |
dc.relation.isreferencedby |
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE132649 |
dc.subject.other |
Mama -- Càncer |
dc.subject.other |
Progesterona |
dc.subject.other |
Proteïnes |
dc.title |
C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells |
dc.type |
info:eu-repo/semantics/article |
dc.identifier.doi |
http://dx.doi.org/10.15252/embj.2018101426 |
dc.relation.projectID |
info:eu-repo/grantAgreement/ES/1PE/SAF2016-75006P |
dc.relation.projectID |
info:eu-repo/grantAgreement/EC/FP7/609989 |
dc.rights.accessRights |
info:eu-repo/semantics/openAccess |
dc.type.version |
info:eu-repo/semantics/acceptedVersion |