Hormone-induced repression of genes requires BRG1-mediated H1.2 deposition at target promoters.
Ana Silvina NachtAndy PohlRoser ZaurinDaniel SoronellasJavier QuilezPriyanka SharmaRoni H WrightMiguel BeatoGuillermo P VicentPublished in: The EMBO journal (2016)
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 ERK1/2 and MSK1. PR recruits BRG1 associated with the HP1γ-LSD1 complex repressor complex, which is further anchored via binding of HP1γ to the H3K9me3 signal deposited by SUV39H2. In contrast to what is observed during gene activation, only BRG1 and not the BAF complex is recruited to repressed promoters, likely due to local enrichment of the pioneer factor FOXA1. BRG1 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 BRG1 in progestin regulation of breast cancer cell growth.
Keyphrases
- transcription factor
- genome wide
- genome wide identification
- cell proliferation
- gene expression
- copy number
- dna methylation
- dna binding
- breast cancer cells
- dna damage
- magnetic resonance imaging
- magnetic resonance
- signaling pathway
- pi k akt
- type diabetes
- genome wide analysis
- cell cycle
- high glucose
- young adults
- endothelial cells
- oxidative stress
- insulin resistance
- adipose tissue
- diabetic rats
- drug induced
- estrogen receptor
- binding protein
- skeletal muscle