Gene silencing by methyl-CpG-binding proteins

Novartis Found Symp. 1998;214:6-16; discussion 16-21, 46-50. doi: 10.1002/9780470515501.ch2.

Abstract

An important consequence of CpG methylation is the local silencing of gene expression. In part this can be mediated by direct interference of methylation with the binding of transcription factors. The major component of silencing, however, appears to be the binding of repressors that have an affinity for methyl-CpG. We have studied two proteins that bind to methylated DNA, methyl-CpG-binding protein 1 (MeCP1) and MeCP2. MeCP2 is a relatively abundant chromosomal protein whose localization in the nucleus is primarily dependent on CpG methylation. We find that MeCP2 is a potent transcriptional repressor with a genome-wide distribution. MeCP1 requires multiple methylated CpGs for binding and has previously been implicated as a methyl-CpG-dependent transcriptional repressor. Recent cloning of a candidate gene for a component of MeCP1 may provide clues to its mechanism of action.

Publication types

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

MeSH terms

  • Animals
  • Chromosomal Proteins, Non-Histone*
  • Cloning, Molecular
  • CpG Islands*
  • DNA Methylation*
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Developmental*
  • Histone Deacetylases*
  • Humans
  • Methyl-CpG-Binding Protein 2
  • Repressor Proteins / metabolism*

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • MECP2 protein, human
  • MeCP1 histone deacetylase complex, human
  • Methyl-CpG-Binding Protein 2
  • Repressor Proteins
  • Histone Deacetylases