Dissecting myogenin-mediated retinoid X receptor signaling in myogenic differentiation

Commun Biol. 2020 Jun 18;3(1):315. doi: 10.1038/s42003-020-1043-9.

Abstract

Deciphering the molecular mechanisms underpinning myoblast differentiation is a critical step in developing the best strategy to promote muscle regeneration in patients suffering from muscle-related diseases. We have previously established that a rexinoid x receptor (RXR)-selective agonist, bexarotene, enhances the differentiation and fusion of myoblasts through a direct regulation of MyoD expression, coupled with an augmentation of myogenin protein. Here, we found that RXR signaling associates with the distribution of myogenin at poised enhancers and a distinct E-box motif. We also found an association of myogenin with rexinoid-responsive gene expression and identified an epigenetic signature related to histone acetyltransferase p300. Moreover, RXR signaling augments residue-specific histone acetylation at enhancers co-occupied by p300 and myogenin. Thus, genomic distribution of transcriptional regulators is an important designate for identifying novel targets as well as developing therapeutics that modulate epigenetic landscape in a selective manner to promote muscle regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Bexarotene / pharmacology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Line
  • Chromatin Immunoprecipitation
  • E1A-Associated p300 Protein / metabolism
  • Enhancer Elements, Genetic
  • Epigenesis, Genetic
  • Histones / metabolism
  • Mice
  • Myoblasts / cytology*
  • Myogenin / genetics
  • Myogenin / metabolism*
  • Retinoid X Receptors / genetics
  • Retinoid X Receptors / metabolism*
  • Signal Transduction

Substances

  • Histones
  • Myog protein, mouse
  • Myogenin
  • Retinoid X Receptors
  • Bexarotene
  • E1A-Associated p300 Protein