Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly

Science. 2001 Apr 6;292(5514):110-3. doi: 10.1126/science.1060118. Epub 2001 Mar 15.

Abstract

The assembly of higher order chromatin structures has been linked to the covalent modifications of histone tails. We provide in vivo evidence that lysine 9 of histone H3 (H3 Lys9) is preferentially methylated by the Clr4 protein at heterochromatin-associated regions in fission yeast. Both the conserved chromo- and SET domains of Clr4 are required for H3 Lys9 methylation in vivo. Localization of Swi6, a homolog of Drosophila HP1, to heterochomatic regions is dependent on H3 Lys9 methylation. Moreover, an H3-specific deacetylase Clr3 and a beta-propeller domain protein Rik1 are required for H3 Lys9 methylation by Clr4 and Swi6 localization. These data define a conserved pathway wherein sequential histone modifications establish a "histone code" essential for the epigenetic inheritance of heterochromatin assembly.

Publication types

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

MeSH terms

  • Acetylation
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Centromere / metabolism
  • Chromosomes, Fungal / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Silencing
  • Genes, Fungal
  • Heterochromatin / metabolism*
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase*
  • Histones / chemistry*
  • Histones / metabolism*
  • Lysine / metabolism*
  • Methylation
  • Methyltransferases / chemistry
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Mutation
  • Protein Methyltransferases
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins*
  • Transcription Factors / metabolism

Substances

  • Cell Cycle Proteins
  • Clr3 protein, S pombe
  • Fungal Proteins
  • Heterochromatin
  • Histones
  • Recombinant Proteins
  • SWI6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins
  • Transcription Factors
  • Histone Methyltransferases
  • Methyltransferases
  • Protein Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • clr4 protein, S pombe
  • Histone Deacetylases
  • Lysine