dc.contributor.author | Nacht, AS | |
dc.contributor.author | Ferrari, R | |
dc.contributor.author | Zaurin, R | |
dc.contributor.author | Scabia, V | |
dc.contributor.author | Carbonell-Caballero, J | |
dc.contributor.author | Le Dily, F | |
dc.contributor.author | Quilez, J | |
dc.contributor.author | Leopoldi, A | |
dc.contributor.author | Brisken, C | |
dc.contributor.author | Beato, M | |
dc.contributor.author | Vicent, GP | |
dc.date.accessioned | 2021-11-19T09:16:42Z | |
dc.date.available | 2021-11-19T09:16:42Z | |
dc.date.issued | 2019-09-16 | |
dc.identifier.citation | The EMBO journal, 2019, 38 (18), pp. e101426 - ? | |
dc.identifier.issn | 0261-4189 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4884 | |
dc.identifier.eissn | 1460-2075 | |
dc.identifier.doi | 10.15252/embj.2018101426 | |
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.format | Print-Electronic | |
dc.format.extent | e101426 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | WILEY | |
dc.subject | Cell Line, Tumor | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Breast Neoplasms | |
dc.subject | Cell Cycle Proteins | |
dc.subject | DNA-Binding Proteins | |
dc.subject | CCAAT-Enhancer-Binding Proteins | |
dc.subject | Receptors, Progesterone | |
dc.subject | Progestins | |
dc.subject | Xenograft Model Antitumor Assays | |
dc.subject | Neoplasm Transplantation | |
dc.subject | Epigenesis, Genetic | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Female | |
dc.subject | YY1 Transcription Factor | |
dc.subject | Enhancer Elements, Genetic | |
dc.subject | Promoter Regions, Genetic | |
dc.subject | Gene Knockdown Techniques | |
dc.subject | MCF-7 Cells | |
dc.title | C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-06-24 | |
rioxxterms.versionofrecord | 10.15252/embj.2018101426 | |
rioxxterms.licenseref.startdate | 2019-09 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | The EMBO journal | |
pubs.issue | 18 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrine control mechanisms | |
pubs.publication-status | Published | |
pubs.volume | 38 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Endocrine control mechanisms | |
dc.contributor.icrauthor | Brisken, Cathrin | |