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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.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Funding
The experimental work was supported by grants from the Departament d’Innovació Universitat i Empresa (DIUiE). We acknowledge support of the Spanish Ministry of Economy and Competitiveness (SAF2013-42497-P), “Centro de Excelencia Severo Ochoa 2013–2017,” SEV-2012-0208, and ERC Synergy Grant “4DGenome” nr 609989.