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Hormone‐induced repression of genes requires BRG 1‐mediated H1.2 deposition at target promoters
Author(s) -
Nacht Ana Silvina,
Pohl Andy,
Zaurin Roser,
Soronellas Daniel,
Quilez Javier,
Sharma Priyanka,
Wright Roni H,
Beato Miguel,
Vicent Guillermo P
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201593260
Subject(s) - biology
Eukaryotic gene regulation is associated with changes in chromatin compaction that modulate access to DNA regulatory sequences relevant for transcriptional activation or repression. Although much is known about the mechanism of chromatin remodeling in hormonal gene activation, how repression is accomplished is much less understood. Here we report that in breast cancer cells, ligand‐activated progesterone receptor ( PR ) is directly recruited to transcriptionally repressed genes involved in cell proliferation along with the kinases ERK 1/2 and MSK 1. PR recruits BRG 1 associated with the HP 1γ‐LSD1 complex repressor complex, which is further anchored via binding of HP 1γ to the H3K9me3 signal deposited by SUV 39H2. In contrast to what is observed during gene activation, only BRG 1 and not the BAF complex is recruited to repressed promoters, likely due to local enrichment of the pioneer factor FOXA 1. BRG 1 participates in gene repression by interacting with H1.2, facilitating its deposition and stabilizing nucleosome positioning around the transcription start site. Our results uncover a mechanism of hormone‐dependent transcriptional repression and a novel role for BRG 1 in progestin regulation of breast cancer cell growth.