The chromatin Remodeler CHD8 is required for activation of progesterone receptor-dependent enhancers. Academic Article uri icon

Overview

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.

publication date

  • April 20, 2015

Research

keywords

  • DNA-Binding Proteins
  • Enhancer Elements, Genetic
  • Receptors, Progesterone
  • Transcription Factors
  • Transcription, Genetic

Identity

PubMed Central ID

  • PMC4403880

Scopus Document Identifier

  • 84930319247

Digital Object Identifier (DOI)

  • 10.1038/nprot.2008.211

PubMed ID

  • 25894978

Additional Document Info

volume

  • 11

issue

  • 4