title: Steroid hormone receptors silence genes by a chromatin-targeted mechanism similar to those used for gene activation.
abstract: How genes are repressed by steroid hormones remains a matter of debate, and several indirect mechanisms have been proposed. We found that the ligand-activated progesterone receptor recruits to the promoter of downregulated genes a repressor complex composed of HP1γ, the lysine demethylase LSD1, histone deacetylases, coREST, the RNA SRA, and the ATPase BRG1. BRG1 is needed for chromatin remodeling and facilitates the deposition of linker histone variant H1.2, which compacts chromatin and hinders RNA polymerase loading and transcription. Thus, steroid hormone receptors can repress genes in ways reminiscent of those used for gene induction, namely by directly targeting factors that remodel chromatin. But while PR-dependent gene induction in T47D cells is mainly achieved by potentiating enhancer activity, repression acts at the level of gene promoters.
authors.affiliation: a Centre de Regulació Genòmica (CRG) , The Barcelona Institute for Science and Technology (BIST) , Barcelona , Spain.|b Gene Regulation , Stem Cells and Cancer Program, Universitat Pompeu Fabra (UPF) , Barcelona , Spain.
authors.forename: A Silvina
authors.initials: AS
authors.lastname: Nacht
authors.affiliation: a Centre de Regulació Genòmica (CRG) , The Barcelona Institute for Science and Technology (BIST) , Barcelona , Spain.|b Gene Regulation , Stem Cells and Cancer Program, Universitat Pompeu Fabra (UPF) , Barcelona , Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Beato
authors.affiliation: a Centre de Regulació Genòmica (CRG) , The Barcelona Institute for Science and Technology (BIST) , Barcelona , Spain.|b Gene Regulation , Stem Cells and Cancer Program, Universitat Pompeu Fabra (UPF) , Barcelona , Spain.
authors.forename: Guillermo P
authors.initials: GP
authors.lastname: Vicent
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly; D053263:Gene Regulatory Networks; D020868:Gene Silencing; D006801:Humans; D011401:Promoter Regions, Genetic; D011987:Receptors, Steroid / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D011987:Receptors, Steroid
keywords: Progesterone receptor; breast cancer; chromatin remodelling; gene repression; histone H1