The myogenic basic helix-loop-helix family of transcription factors shows similar requirements for SWI/SNF chromatin remodeling enzymes during muscle differentiation in culture

J Biol Chem. 2002 Sep 13;277(37):33818-24. doi: 10.1074/jbc.M205159200. Epub 2002 Jul 8.

Abstract

The myogenic basic helix-loop-helix family of transcription factors, MyoD, Myf5, myogenin, and MRF4, can each activate the muscle differentiation program when ectopically expressed in non-muscle cells. SWI/SNF complexes are ATP-dependent chromatin remodeling enzymes. We demonstrated previously that SWI/SNF enzymes promote MyoD-mediated muscle differentiation. To ascertain the requirement for SWI/SNF enzymes in muscle differentiation mediated by different MyoD family members, we examined MyoD, Myf5, MRF4, and myogenin-mediated induction of muscle differentiation in cells expressing dominant negative versions of BRG1 or BRM-based SWI/SNF enzymes. We demonstrated that expression of dominant negative BRG1 or BRM inhibited the induction of muscle-specific gene expression by Myf5 and MRF4; however, myogenin failed to induce measurable quantities of muscle-specific mRNAs, even in cells not expressing dominant negative SWI/SNF. In contrast, all four myogenic regulators induced expression of the cell cycle regulators p21, Rb, and cyclin D3 and promoted cell cycle arrest independently of the SWI/SNF enzymes. We proposed that SWI/SNF enzymes are required for the induction of all muscle-specific gene expression by MyoD, Myf5, and MRF4, whereas induction of the cell cycle regulators, p21, Rb, and cyclin D3 occurred independently of SWI/SNF function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Cycle
  • Cell Differentiation
  • Chromatin / metabolism*
  • Chromosomal Proteins, Non-Histone / physiology*
  • Cyclin D3
  • Cyclins / analysis
  • DNA-Binding Proteins*
  • Gene Expression Regulation, Developmental
  • Helix-Loop-Helix Motifs
  • Humans
  • Mice
  • Muscle Proteins / physiology*
  • Muscle, Skeletal / embryology*
  • MyoD Protein / physiology*
  • Myogenic Regulatory Factor 5
  • Myogenic Regulatory Factors / physiology*
  • Myogenin / physiology
  • Trans-Activators*
  • Transcription Factors / physiology*

Substances

  • CCND3 protein, human
  • Ccnd3 protein, mouse
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Cyclin D3
  • Cyclins
  • DNA-Binding Proteins
  • MYF5 protein, human
  • MYOG protein, human
  • Muscle Proteins
  • Myf5 protein, mouse
  • MyoD Protein
  • Myog protein, mouse
  • Myogenic Regulatory Factor 5
  • Myogenic Regulatory Factors
  • Myogenin
  • SWI-SNF-B chromatin-remodeling complex
  • Trans-Activators
  • Transcription Factors
  • myogenic factor 6