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Elife. 2018 May 24;7. pii: e35073. doi: 10.7554/eLife.35073.

BRG1 governs glucocorticoid receptor interactions with chromatin and pioneer factors across the genome.

Author information

1
Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina, United States.
2
Integrative Bioinformatics, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina, United States.
#
Contributed equally

Abstract

The Glucocorticoid Receptor (GR) alters transcriptional activity in response to hormones by interacting with chromatin at GR binding sites (GBSs) throughout the genome. Our work in human breast cancer cells identifies three classes of GBSs with distinct epigenetic characteristics and reveals that BRG1 interacts with GBSs prior to hormone exposure. The GBSs pre-occupied by BRG1 are more accessible and transcriptionally active than other GBSs. BRG1 is required for a proper and robust transcriptional hormone response and knockdown of BRG1 blocks recruitment of the pioneer factors FOXA1 and GATA3 to GBSs. Finally, GR interaction with FOXA1 and GATA3 binding sites was restricted to sites pre-bound by BRG1. These findings demonstrate that BRG1 establishes specialized chromatin environments that define multiple classes of GBS. This in turn predicts that GR and other transcriptional activators function via multiple distinct chromatin-based mechanisms to modulate the transcriptional response.

KEYWORDS:

brg1; chromatin; chromosomes; gene expression; glucocorticoid receptor; histone modifications; human; pioneer factors; transcription factors

PMID:
29792595
PMCID:
PMC5967868
DOI:
10.7554/eLife.35073
[Indexed for MEDLINE]
Free PMC Article

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