C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells.
EMBO J
; 38(18): e101426, 2019 09 16.
Article
in En
| MEDLINE
| ID: mdl-31373033
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Receptors, Progesterone
/
CCAAT-Enhancer-Binding Proteins
Type of study:
Prognostic_studies
Language:
En
Journal:
EMBO J
Year:
2019
Type:
Article
Affiliation country:
Spain