LSD1 Controls Timely MyoD Expression via MyoD Core Enhancer Transcription

• Published in: Cell reports (Cambridge) Vol. 18; no. 8; pp. 1996 - 2006
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21-02-2017; Elsevier
• Subjects: Animals; Biochemistry, Molecular Biology; Cell Differentiation - physiology; Cells, Cultured; chromatin-modifying enzyme; enhancer RNA; Gene Expression Regulation, Developmental - physiology; Genomics; Histone Demethylases - metabolism; Histones - metabolism; Life Sciences; Limb Buds - metabolism; LSD1; Mice; muscle; Muscle Development - physiology; Myoblasts - metabolism; Myoblasts - physiology; MyoD; MyoD Protein - metabolism; Regulatory Sequences, Nucleic Acid - physiology; RNA Polymerase II - metabolism; Transcription, Genetic - physiology; enhancer RNA; MyoD; LSD1; muscle; chromatin-modifying enzyme
• ISSN: 2211-1247; 2211-1247
• 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.
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•LSD1 participates in enhancer function by promoting eRNA transcription•LSD1 contributes to activate MyoD during commitment of muscle cells•LSD1 is recruited on the MyoD core enhancer (CE) during muscle differentiation•LSD1 activates the transcription of the MyoD core enhancer eRNA
Scionti et al. show that LSD1 is recruited on the MyoD core enhancer, where it promotes the transcription of an enhancer RNA that controls the timing of MyoD expression during myoblast commitment. This provides the first evidence that LSD1 is required for the transcription of enhancer RNAs from a pro-differentiation enhancer.