1. ERRα induces H3K9 demethylation by LSD1 to promote cell invasion
- Author
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Christelle Forcet, Violaine Tribollet, Jason S. Carroll, Julie Carnesecchi, Jean-Marc Vanacker, Catherine Cerutti, Rafik Boudra, Bruno Barenton, Ling Zhang, Isabelle M. L. Billas, Aurélien A. Sérandour, Claude Beaudoin, Centre for Advanced Macromolecular Design (CAMD), University of New South Wales [Sydney] (UNSW), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Agressions vasculaires et réponses tissulaires, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Cancer Research UK [Cambridge, UK] (Cambridge Institute), University of Cambridge [UK] (CAM), Genotypes et Phenotypes Tumoraux, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,animal structures ,MMP1 ,cell migration ,LSD1 ,Methylation ,Histones ,03 medical and health sciences ,Histone H3 ,0302 clinical medicine ,Cell Movement ,Humans ,transcriptional regulation ,Receptor ,Promoter Regions, Genetic ,Gene ,Demethylation ,Histone Demethylases ,Multidisciplinary ,biology ,histone demethylation ,Chemistry ,Lysine ,Biological Sciences ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,Cell biology ,030104 developmental biology ,Histone ,HEK293 Cells ,Nuclear receptor ,Gene Expression Regulation ,Receptors, Estrogen ,ERR alpha ,030220 oncology & carcinogenesis ,biology.protein ,Demethylase ,Matrix Metalloproteinase 1 ,Transcription Initiation Site - Abstract
International audience; Lysine Specific Demethylase 1 (LSD1) removes mono-and dimethyl groups from lysine 4 of histone H3 (H3K4) or H3K9, resulting in repressive or activating (respectively) transcriptional histone marks. The mechanisms that control the balance between these two antagonist activities are not understood. We here show that LSD1 and the orphan nuclear receptor estrogen-related receptor a (ERR alpha) display commonly activated genes. Transcriptional activation by LSD1 and ERR alpha involves H3K9 demethylation at the transcriptional start site (TSS). Strikingly, ERR alpha is sufficient to induce LSD1 to demethylate H3K9 in vitro. The relevance of this mechanism is highlighted by functional data. LSD1 and ERR alpha coregulate several target genes involved in cell migration, including the MMP1 matrix metallo-protease, also activated through H3K9 demethylation at the TSS. Depletion of LSD1 or ERR alpha reduces the cellular capacity to invade the extracellular matrix, a phenomenon that is rescued by MMP1 reexpression. Altogether our results identify a regulatory network involving a direct switch in the biochemical activities of a histone demethylase, leading to increased cell invasion.
- Published
- 2017
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