title: Hormone-induced repression of genes requires BRG1-mediated H1.2 deposition at target promoters.
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.
authors.affiliation: Centre de Regulació Genòmica (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Ana Silvina
authors.initials: AS
authors.lastname: Nacht
authors.affiliation: Centre de Regulació Genòmica (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Andy
authors.initials: A
authors.lastname: Pohl
authors.affiliation: Centre de Regulació Genòmica (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Zaurin
authors.affiliation: Centre de Regulació Genòmica (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Soronellas
authors.affiliation: Centre de Regulació Genòmica (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Quilez
authors.affiliation: Centre de Regulació Genòmica (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Centre de Regulació Genòmica (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Roni H
authors.initials: RH
authors.lastname: Wright
authors.affiliation: Centre de Regulació Genòmica (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain miguel.beato@crg.eu guillermo.vicent@crg.eu.
authors.forename: Miguel
authors.initials: M
authors.lastname: Beato
authors.affiliation: Centre de Regulació Genòmica (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain miguel.beato@crg.eu guillermo.vicent@crg.eu.
authors.forename: Guillermo P
authors.identifier: 0000-0002-0554-2226
authors.initials: GP
authors.lastname: Vicent
mesh_terms: D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D006657:Histones; D006728:Hormones; D009687:Nuclear Proteins; D014157:Transcription Factors; D004247:DNA; C084108:SMARCA4 protein, human; D004265:DNA Helicases
keywords: BRG1; H1.2; chromatin remodeling; hormone‐dependent gene repression