Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin

Mol Cell Biol. 2005 Jan;25(1):364-76. doi: 10.1128/MCB.25.1.364-376.2005.

Abstract

Differentiation of smooth muscle cells is accompanied by the transcriptional activation of an array of muscle-specific genes controlled by serum response factor (SRF). Myocardin is a cardiac and smooth muscle-specific expressed transcriptional coactivator of SRF and is sufficient and necessary for smooth muscle gene expression. Here, we show that myocardin induces the acetylation of nucleosomal histones surrounding SRF-binding sites in the control regions of smooth muscle genes. The promyogenic activity of myocardin is enhanced by p300, a histone acetyltransferase that associates with the transcription activation domain of myocardin. Conversely, class II histone deacetylases interact with a domain of myocardin distinct from the p300-binding domain and suppress smooth muscle gene activation by myocardin. These findings point to myocardin as a nexus for positive and negative regulation of smooth muscle gene expression by changes in chromatin acetylation.

Publication types

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

MeSH terms

  • Acetylation
  • Acetyltransferases / metabolism*
  • Animals
  • COS Cells
  • Cardiovascular System / cytology
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation
  • Cell Line
  • Chromatin / metabolism
  • Gene Expression Regulation*
  • Glutathione Transferase / metabolism
  • Histone Acetyltransferases
  • Histone Deacetylases / metabolism*
  • Histones / metabolism
  • Immunoprecipitation
  • Lac Operon
  • Luciferases / metabolism
  • Mice
  • Models, Genetic
  • Muscle, Smooth / metabolism*
  • Myocytes, Smooth Muscle / cytology
  • Nuclear Proteins / metabolism*
  • Nucleosomes / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Trans-Activators / metabolism*
  • Transcription Factors
  • Transcription, Genetic
  • Transcriptional Activation
  • Transfection
  • p300-CBP Transcription Factors

Substances

  • Cell Cycle Proteins
  • Chromatin
  • Histones
  • Nuclear Proteins
  • Nucleosomes
  • Trans-Activators
  • Transcription Factors
  • myocardin
  • Luciferases
  • Acetyltransferases
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Glutathione Transferase
  • Histone Deacetylases