MyoD acetylation influences temporal patterns of skeletal muscle gene expression

J Biol Chem. 2007 Dec 28;282(52):37650-9. doi: 10.1074/jbc.M707309200. Epub 2007 Oct 27.

Abstract

MyoD is sufficient to initiate the skeletal muscle gene expression program. Transcription of certain MyoD target genes occurs in the early phases, whereas that of others is induced only at later stages, although MyoD is present throughout the differentiation process. MyoD acetylation regulates transcriptional competency, yet whether this post-translational modification is equally relevant for activation of all the MyoD targets is unknown. Moreover, the molecular mechanisms through which acetylation ensures that MyoD achieves its optimal activity remain unexplored. To address these two outstanding issues, we have coupled genome-wide expression profiling and chromatin immunoprecipitation in a model system in which MyoD or its nonacetylatable version was inducibly activated in mouse embryonic fibroblasts derived from MyoD(-/-)/Myf5(-/-) mice. Our results reveal that MyoD acetylation influences transcription of selected genes expressed at defined stages of the muscle program by regulating chromatin access of MyoD, histone acetylation, and RNA polymerase II recruitment.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Lineage
  • Chromatin / metabolism
  • Fibroblasts / metabolism
  • Gene Expression Regulation, Developmental*
  • Genome
  • Mice
  • Mice, Transgenic
  • Models, Genetic
  • Muscle, Skeletal / metabolism*
  • MyoD Protein / metabolism*
  • MyoD Protein / physiology*
  • Protein Processing, Post-Translational
  • RNA Polymerase II / metabolism
  • Time Factors
  • Transcription, Genetic

Substances

  • Chromatin
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • RNA Polymerase II