LSD1 Controls Timely MyoD Expression via MyoD Core Enhancer Transcription

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.

Keywords: LSD1; MyoD; chromatin-modifying enzyme; enhancer RNA; muscle.

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Gene Expression Regulation, Developmental / physiology
  • Histone Demethylases / metabolism*
  • Histones / metabolism
  • Limb Buds / metabolism
  • Mice
  • Muscle Development / physiology
  • MyoD Protein / metabolism*
  • Myoblasts / metabolism
  • Myoblasts / physiology
  • RNA Polymerase II / metabolism
  • Regulatory Sequences, Nucleic Acid / physiology
  • Transcription, Genetic / physiology*


  • Histones
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Histone Demethylases
  • KDM1a protein, mouse
  • RNA Polymerase II