Title | The chromatin Remodeler CHD8 is required for activation of progesterone receptor-dependent enhancers. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Ceballos-Chávez M, Subtil-Rodríguez A, Giannopoulou EG, Soronellas D, Vázquez-Chávez E, Vicent GP, Elemento O, Beato M, Reyes JC |
Journal | PLoS Genet |
Volume | 11 |
Issue | 4 |
Pagination | e1005174 |
Date Published | 2015 Apr |
ISSN | 1553-7404 |
Keywords | Acetylation, Chromatin, Chromatin Assembly and Disassembly, Chromosomal Proteins, Non-Histone, DNA Helicases, DNA-Binding Proteins, Enhancer Elements, Genetic, Gene Expression Regulation, Hepatocyte Nuclear Factor 3-alpha, Humans, Promoter Regions, Genetic, Protein Binding, Receptors, Progesterone, RNA Polymerase II, Transcription Factors, Transcription, Genetic |
Abstract | 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. |
DOI | 10.1371/journal.pgen.1005174 |
Alternate Journal | PLoS Genet. |
PubMed ID | 25894978 |
PubMed Central ID | PMC4403880 |