Scionti Isabella, Hayashi Shinichiro, Mouradian Sandrine, Girard Emmanuelle, Esteves de Lima Joana, Morel Véronique, Simonet Thomas, Wurmser Maud, Maire Pascal, Ancelin Katia, Metzger Eric, Schüle Roland, Goillot Evelyne, Relaix Frederic, Schaeffer Laurent
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.
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.
Cell Rep. 2017 Feb 21;18(8):1996-2006. doi: 10.1016/j.celrep.2017.01.078.
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.
肌分化决定因子（MyoD）是成肌作用的主要调节因子。触发MyoD表达所需的染色质修饰仍鲜有描述。在此，我们证明，在肌肉分化过程中，组蛋白去甲基化酶赖氨酸特异性去甲基化酶1（LSD1）/赖氨酸特异性组蛋白去甲基化酶1A（KDM1a）被招募至MyoD核心增强子上。成肌细胞中Lsd1的缺失会阻止H3K9甲基化的去除以及RNA聚合酶II在核心增强子上的募集，从而阻碍MyoD表达所需的非编码增强子RNA（CEeRNA）的转录。同样，胚胎发育过程中肌肉祖细胞中Lsd1的条件性失活会阻止CEeRNA的转录并延迟MyoD的表达。我们的结果表明，LSD1是肢体芽中MyoD及时表达所必需的，并通过证明其可激活增强子的RNA聚合酶II依赖性转录，确定了LSD1的一种新生物学功能。
