2024-03-28T20:19:36Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1236572021-06-07T06:56:52Zcom_10261_134com_10261_1col_10261_387
Ceballos-Chávez, María
Subtil-Rodríguez, Alicia
Giannopoulou, Eugenia G.
Soronellas, Daniel
Vázquez-Chávez, Elena
Vicent, Guillermo P.
Elemento, Olivier
Beato, Miguel
Reyes, José C.
2015-10-21T09:29:14Z
2015-10-21T09:29:14Z
2015-04-20
PLoS Genetics 11(4): e1005174 (2015)
http://hdl.handle.net/10261/123657
10.1371/journal.pgen.1005174
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/100008054
http://dx.doi.org/10.13039/501100002809
http://dx.doi.org/10.13039/501100003339
http://dx.doi.org/10.13039/501100011011
25894978
While the importance of gene enhancers in transcriptional regulation is well established, the mechanisms and the protein factors that determine enhancers activity have only recently begun to be unravelled. Recent studies have shown that progesterone receptor (PR) binds regions that display typical features of gene enhancers. Here, we show by ChIP-seq experiments that the chromatin remodeler CHD8 mostly binds promoters under proliferation conditions. However, upon progestin stimulation, CHD8 re-localizes to PR enhancers also enriched in p300 and H3K4me1. Consistently, CHD8 depletion severely impairs progestin-dependent gene regulation. CHD8 binding is PR-dependent but independent of the pioneering factor FOXA1. The SWI/SNF chromatin-remodelling complex is required for PR-dependent gene activation. Interestingly, we show that CHD8 interacts with the SWI/SNF complex and that depletion of BRG1 and BRM, the ATPases of SWI/SNF complex, impairs CHD8 recruitment. We also show that CHD8 is not required for H3K27 acetylation, but contributes to increase accessibility of the enhancer to DNaseI. Furthermore, CHD8 was required for RNAPII recruiting to the enhancers and for transcription of enhancer-derived RNAs (eRNAs). Taken together our data demonstrate that CHD8 is involved in late stages of PR enhancers activation.
eng
http://creativecommons.org/licenses/by/4.0/
openAccess
The Chromatin Remodeler CHD8 Is Required for Activation of Progesterone Receptor-Dependent Enhancers
artículo