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Cell Rep. 2017 Feb 21;18(8):1996-2006. doi: 10.1016/j.celrep.2017.01.078.

LSD1 Controls Timely MyoD Expression via MyoD Core Enhancer Transcription.

Author information

1
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.
2
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.
3
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.
4
Biology of the Neuromuscular System, INSERM IMRB-E10 U955, Université Paris-Est, 8 rue du Général Sarrail, 94010 Créteil Cedex, France.
5
Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, Sorbonne Paris Cité, 22 rue Mechain, 75014 Paris, France.
6
Institut NeuroMyoGene, CNRS UMR5310, INSERM U1217, Université Lyon1, 46 Allée d'Italie, 69007 Lyon, France.
7
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.
8
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.
9
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.

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.

KEYWORDS:

LSD1; MyoD; chromatin-modifying enzyme; enhancer RNA; muscle

PMID:
28228264
DOI:
10.1016/j.celrep.2017.01.078
[Indexed for MEDLINE]
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