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Title

C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells

AuthorsNacht, A. Silvina; Ferrari, Roberto; Zaurin, Roser; Scabia, Valentina; Carbonell‐Caballero, José; Le Dily, Francois; Quilez, Javier CSIC ORCID; Leopoldi, Alexandra; Brisken, Cathrin; Beato, Miguel; Vicent, Guillermo P. CSIC ORCID
Issue Date16-Sep-2019
PublisherEMBO Press
CitationEMBO Journal 38(18): e101426 (2019)
AbstractSteroid 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.
Publisher version (URL)http://dx.doi.org/10.15252/embj.2018101426
URIhttp://hdl.handle.net/10261/201382
DOI10.15252/embj.2018101426
ISSN0261-4189
E-ISSN1460-2075
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