title: LSD1 Controls Timely MyoD Expression via MyoD Core Enhancer Transcription.
abstract: MyoD is a master regulator of myogenesis. Chromatin modifications required to trigger MyoD expression are still poorly described. Here, we demonstrate that the histone demethylase LSD1/KDM1a is recruited on the MyoD core enhancer upon muscle differentiation. Depletion of Lsd1 in myoblasts precludes the removal of H3K9 methylation and the recruitment of RNA polymerase II on the core enhancer, thereby preventing transcription of the non-coding enhancer RNA required for MyoD expression (CEeRNA). Consistently, Lsd1 conditional inactivation in muscle progenitor cells during embryogenesis prevented transcription of the CEeRNA and delayed MyoD expression. Our results demonstrate that LSD1 is required for the timely expression of MyoD in limb buds and identify a new biological function for LSD1 by showing that it can activate RNA polymerase II-dependent transcription of enhancers.
authors.affiliation: Institut NeuroMyoGene, CNRS UMR5310, INSERM U1217, Université Lyon1, 46 Allée d'Italie, 69007 Lyon, France; Laboratory of Molecular Biology of the Cell, CNRS UMR5239, Université Lyon 1, ENS Lyon, 46 Allée d'Italie, 69007 Lyon, France.
authors.forename: Isabella
authors.initials: I
authors.lastname: Scionti
authors.affiliation: Biology of the Neuromuscular System, INSERM IMRB-E10 U955, Université Paris-Est, 8 rue du Général Sarrail, 94010 Créteil Cedex, France; Department of Cellular and Molecular Medicine, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Institut NeuroMyoGene, CNRS UMR5310, INSERM U1217, Université Lyon1, 46 Allée d'Italie, 69007 Lyon, France; Laboratory of Molecular Biology of the Cell, CNRS UMR5239, Université Lyon 1, ENS Lyon, 46 Allée d'Italie, 69007 Lyon, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Mouradian
authors.affiliation: Institut NeuroMyoGene, CNRS UMR5310, INSERM U1217, Université Lyon1, 46 Allée d'Italie, 69007 Lyon, France; Laboratory of Molecular Biology of the Cell, CNRS UMR5239, Université Lyon 1, ENS Lyon, 46 Allée d'Italie, 69007 Lyon, France; Hospices Civils de Lyon, Faculté de Medicine Lyon Est, 3 Quai des Célestins, 69002 Lyon, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Girard
authors.affiliation: Biology of the Neuromuscular System, INSERM IMRB-E10 U955, Université Paris-Est, 8 rue du Général Sarrail, 94010 Créteil Cedex, France.
authors.forename: Joana
authors.initials: J
authors.lastname: Esteves de Lima
authors.affiliation: Institut NeuroMyoGene, CNRS UMR5310, INSERM U1217, Université Lyon1, 46 Allée d'Italie, 69007 Lyon, France; Laboratory of Molecular Biology of the Cell, CNRS UMR5239, Université Lyon 1, ENS Lyon, 46 Allée d'Italie, 69007 Lyon, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Morel
authors.affiliation: Institut NeuroMyoGene, CNRS UMR5310, INSERM U1217, Université Lyon1, 46 Allée d'Italie, 69007 Lyon, France; Laboratory of Molecular Biology of the Cell, CNRS UMR5239, Université Lyon 1, ENS Lyon, 46 Allée d'Italie, 69007 Lyon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Simonet
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, Sorbonne Paris Cité, 22 rue Mechain, 75014 Paris, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Wurmser
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, Sorbonne Paris Cité, 22 rue Mechain, 75014 Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Maire
authors.affiliation: Institut NeuroMyoGene, CNRS UMR5310, INSERM U1217, Université Lyon1, 46 Allée d'Italie, 69007 Lyon, France.
authors.forename: Katia
authors.initials: K
authors.lastname: Ancelin
authors.affiliation: Klinik für Urologie und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany; Deutsches Konsortium für Translationale Krebsforschung, Standort Freiburg, 79106 Freiburg, Germany; BIOSS Centre of Biological Signalling Studies, Albert Ludwigs University Freiburg, 79106 Freiburg, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Metzger
authors.affiliation: Klinik für Urologie und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany; Deutsches Konsortium für Translationale Krebsforschung, Standort Freiburg, 79106 Freiburg, Germany; BIOSS Centre of Biological Signalling Studies, Albert Ludwigs University Freiburg, 79106 Freiburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Schüle
authors.affiliation: Institut NeuroMyoGene, CNRS UMR5310, INSERM U1217, Université Lyon1, 46 Allée d'Italie, 69007 Lyon, France; Laboratory of Molecular Biology of the Cell, CNRS UMR5239, Université Lyon 1, ENS Lyon, 46 Allée d'Italie, 69007 Lyon, France. Electronic address: evelyne.goillot@ens-lyon.fr.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Goillot
authors.affiliation: Biology of the Neuromuscular System, INSERM IMRB-E10 U955, Université Paris-Est, 8 rue du Général Sarrail, 94010 Créteil Cedex, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Relaix
authors.affiliation: Institut NeuroMyoGene, CNRS UMR5310, INSERM U1217, Université Lyon1, 46 Allée d'Italie, 69007 Lyon, France; Laboratory of Molecular Biology of the Cell, CNRS UMR5239, Université Lyon 1, ENS Lyon, 46 Allée d'Italie, 69007 Lyon, France; Hospices Civils de Lyon, Faculté de Medicine Lyon Est, 3 Quai des Célestins, 69002 Lyon, France. Electronic address: laurent.schaeffer@univ-lyon1.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Schaeffer
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D056466:Histone Demethylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D018878:Limb Buds / Q000378:metabolism; D051379:Mice; D024510:Muscle Development / Q000502:physiology; D017570:MyoD Protein / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism / Q000502:physiology; D012319:RNA Polymerase II / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D006657:Histones; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D056466:Histone Demethylases; C504076:KDM1a protein, mouse; D012319:RNA Polymerase II
keywords: LSD1; MyoD; chromatin-modifying enzyme; enhancer RNA; muscle