Myod1 and GR coordinate myofiber-specific transcriptional enhancers

Nucleic Acids Res. 2021 May 7;49(8):4472-4492. doi: 10.1093/nar/gkab226.


Skeletal muscle is a dynamic tissue the size of which can be remodeled through the concerted actions of various cues. Here, we investigated the skeletal muscle transcriptional program and identified key tissue-specific regulatory genetic elements. Our results show that Myod1 is bound to numerous skeletal muscle enhancers in collaboration with the glucocorticoid receptor (GR) to control gene expression. Remarkably, transcriptional activation controlled by these factors occurs through direct contacts with the promoter region of target genes, via the CpG-bound transcription factor Nrf1, and the formation of Ctcf-anchored chromatin loops, in a myofiber-specific manner. Moreover, we demonstrate that GR negatively controls muscle mass and strength in mice by down-regulating anabolic pathways. Taken together, our data establish Myod1, GR and Nrf1 as key players of muscle-specific enhancer-promoter communication that orchestrate myofiber size regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation Sequencing
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation / genetics
  • Histones / genetics
  • Histones / metabolism
  • Male
  • Metabolic Networks and Pathways / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Strength / genetics
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / physiology
  • MyoD Protein / genetics
  • MyoD Protein / metabolism*
  • Myoblasts / metabolism
  • Nuclear Respiratory Factor 1 / genetics
  • Nuclear Respiratory Factor 1 / metabolism*
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism*
  • Recombinant Proteins


  • Chromatin
  • Histones
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Nrf1 protein, mouse
  • Nuclear Respiratory Factor 1
  • Receptors, Glucocorticoid
  • Recombinant Proteins
  • histone H3 trimethyl Lys4