MyoD targets TAF3/TRF3 to activate myogenin transcription

Mol Cell. 2008 Oct 10;32(1):96-105. doi: 10.1016/j.molcel.2008.09.009.

Abstract

Skeletal muscle differentiation requires a cascade of transcriptional events to control the spatial and temporal expression of muscle-specific genes. Until recently, muscle-specific transcription was primarily attributed to prototypic enhancer-binding factors, while the role of core promoter recognition complexes in directing myogenesis remained unknown. Here, we report the development of a purified reconstituted system to analyze the properties of a TAF3/TRF3 complex in directing transcription initiation at the Myogenin promoter. Importantly, this new complex is required to replace the canonical TFIID to recapitulate MyoD-dependent activation of Myogenin. In vitro and cell-based assays identify a domain of TAF3 that mediates coactivator functions targeted by MyoD. Our findings also suggest changes to CRSP/Mediator in terminally differentiated myotubes. This switching of the core promoter recognition complex during myogenesis allows a more balanced division of labor between activators and TAF coactivators, thus providing another strategy to accommodate cell-specific regulation during metazoan development.

MeSH terms

  • Animals
  • Cell Line
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / metabolism*
  • In Vitro Techniques
  • Mice
  • Multiprotein Complexes
  • Muscle Fibers, Skeletal / metabolism
  • MyoD Protein / metabolism*
  • Myogenin / genetics*
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Protein Subunits
  • Recombinant Proteins / metabolism
  • TATA Box Binding Protein-Like Proteins / metabolism*
  • TATA-Binding Protein Associated Factors
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism
  • Transcription Factor TFIID / metabolism
  • Transcription Initiation Site
  • Transcriptional Activation

Substances

  • Homeodomain Proteins
  • Multiprotein Complexes
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Myog protein, mouse
  • Myogenin
  • Protein Subunits
  • Recombinant Proteins
  • TATA Box Binding Protein-Like Proteins
  • TATA-Binding Protein Associated Factors
  • TRF3 protein, mouse
  • Taf3 protein, mouse
  • Trans-Activators
  • Transcription Factor TFIID