Disordered region of H3K9 methyltransferase Clr4 binds the nucleosome and contributes to its activity

Nucleic Acids Res. 2019 Jul 26;47(13):6726-6736. doi: 10.1093/nar/gkz480.


Heterochromatin is a distinctive chromatin structure that is essential for chromosome segregation, genome stability and regulation of gene expression. H3K9 methylation (H3K9me), a hallmark of heterochromatin, is deposited by the Su(var)3-9 family of proteins; however, the mechanism by which H3K9 methyltransferases bind and methylate the nucleosome is poorly understood. In this work we determined the interaction of Clr4, the fission yeast H3K9 methyltransferase, with nucleosomes using nuclear magnetic resonance, biochemical and genetic assays. Our study shows that the Clr4 chromodomain binds the H3K9me3 tail and that both, the chromodomain and the disordered region connecting the chromodomain and the SET domain, bind the nucleosome core. We show that interaction of the disordered region with the nucleosome core is independent of H3K9me and contributes to H3K9me in vitro and in vivo. Moreover, we show that those interactions with the nucleosome core are contributing to de novo deposition of H3K9me and to establishment of heterochromatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • DNA, Fungal / metabolism*
  • Gene Deletion
  • Heterochromatin / metabolism*
  • Heterochromatin / ultrastructure
  • Histone Code*
  • Histone-Lysine N-Methyltransferase / chemistry
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Methyltransferases / chemistry
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Models, Molecular
  • Mutagenesis, Insertional
  • Mutation, Missense
  • Nucleic Acid Conformation
  • Nucleosomes / metabolism*
  • Protein Binding
  • Protein Conformation
  • Protein Domains
  • Protein Interaction Mapping
  • RNA, Fungal / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / growth & development
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*


  • Cell Cycle Proteins
  • DNA, Fungal
  • Heterochromatin
  • Nucleosomes
  • RNA, Fungal
  • Recombinant Fusion Proteins
  • Schizosaccharomyces pombe Proteins
  • Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • clr4 protein, S pombe