Hormone-induced repression of genes requires BRG1-mediated H1.2 deposition at target promoters
Author
Nacht, Ana Silvina
Pohl, Andy
Zaurín Quer, Roser
Soronellas, Daniel
Quilez Oliete, Javier
SHARMA, PRIYANKA
Wright, Roni
Beato, Miguel
Vincent, Guillermo P.
Publication date
2016ISSN
0261-4189
Abstract
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.
Document Type
Article
Document version
Preliminary Edition
Language
English
Subject (CDU)
57 - Biological sciences in general
Keywords
ADN
Expressió gènica
Histones
Hormones
ADN
Expresión génica
Histonas
Hormonas
DNA
Gene expression
Histones
Hormones
Pages
22
Publisher
EMBO Press
Collection
35;
Is part of
The EMBO Journal
Citation
Nacht, A. Silvina; Pohl, Andy; Zaurín Quer, Roser [et al.]. Hormone-induced repression of genes requires BRG1-mediated H1.2 deposition at target promoters. EMBO J., 2016, 35(16), 1822-1843. Disponible en: <https://www.embopress.org/doi/full/10.15252/embj.201593260>. Fecha de acceso: 26 ene. 2022. DOI: 10.15252/embj.201593260
Grant agreement number
info:eu-repo/grantAgreement/ES/1PE/SAF2013-42497-P
info:eu-repo/grantAgreement/EC/FP7/609989
This item appears in the following Collection(s)
- Ciències Bàsiques [65]
Rights
© 2016, A. Silvina Nacht et al.