Cabin1 represses MEF2 transcriptional activity by association with a methyltransferase, SUV39H1

J Biol Chem. 2007 Apr 13;282(15):11172-9. doi: 10.1074/jbc.M611199200. Epub 2006 Dec 17.

Abstract

Myocyte enhancer factor 2 (MEF2) plays pivotal roles in various biological processes, and its transcriptional activity is regulated by histone acetylation/deacetylation enzymes in a calcium-dependent fashion. A calcineurin-binding protein 1 (Cabin1) has been shown to participate in repression of MEF2 by recruiting mSin3 and its associated histone deacetylases. Here, we report that histone methylation also takes a part in Cabin1-mediated repression of MEF2. Immunoprecipitate of Cabin1 complex can methylate histone H3 by association with SUV39H1. SUV39H1 increased Cabin1-mediated repression of MEF2 transcriptional activity in MEF2-targeting promoters. The SUV39H1 was revealed to bind to the 501-900-amino acid region of Cabin1, which was distinct from its histone deacetylase-recruiting domain. In addition, the Gal4-Cabin1-(501-900) alone repressed a constitutively active Gal4-tk-promoter, indicating that Cabin1 recruits SUV39H1 and represses transcriptional activity. Finally, both SUV39H1 and Cabin1 were shown to bind on the MEF2 target promoter in a calcium-dependent manner. Thus, Cabin1 recruits chromatin-modifying enzymes, both histone deacetylases and a histone methyltransferase, to repress MEF2 transcriptional activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / genetics
  • Amino Acids / metabolism
  • Calcium / metabolism
  • Cell Line
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Humans
  • MEF2 Transcription Factors
  • Myogenic Regulatory Factors / genetics*
  • Myogenic Regulatory Factors / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Protein Methyltransferases
  • Transcription, Genetic / genetics*

Substances

  • Amino Acids
  • MEF2 Transcription Factors
  • Myogenic Regulatory Factors
  • Phosphoproteins
  • Histone Methyltransferases
  • Protein Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Calcium