Differential phosphorylation of Clr4SUV39H by Cdk1 accompanies a histone H3 methylation switch that is essential for gametogenesis

EMBO Rep. 2023 Jan 9;24(1):e55928. doi: 10.15252/embr.202255928. Epub 2022 Nov 21.


Methylation of histone H3 at lysine 9 (H3K9) is a hallmark of heterochromatin that plays crucial roles in gene silencing, genome stability, and chromosome segregation. In Schizosaccharomyces pombe, Clr4 mediates both di- and tri-methylation of H3K9. Although H3K9 methylation has been intensely studied in mitotic cells, its role during sexual differentiation remains unclear. Here, we map H3K9 methylation genome-wide during meiosis and show that constitutive heterochromatin temporarily loses H3K9me2 and becomes H3K9me3 when cells commit to meiosis. Cells lacking the ability to tri-methylate H3K9 exhibit meiotic chromosome segregation defects. Finally, the H3K9 methylation switch is accompanied by differential phosphorylation of Clr4 by the cyclin-dependent kinase Cdk1. Our results suggest that a conserved master regulator of the cell cycle controls the specificity of an H3K9 methyltransferase to prevent ectopic H3K9 methylation and to ensure faithful gametogenesis.

Keywords: chromosome segregation; fission yeast; histone methylation; meiosis; phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Gametogenesis / genetics
  • Heterochromatin / metabolism
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / genetics
  • Histones / metabolism
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Phosphorylation
  • Schizosaccharomyces pombe Proteins* / genetics
  • Schizosaccharomyces pombe Proteins* / metabolism
  • Schizosaccharomyces* / genetics
  • Schizosaccharomyces* / metabolism


  • Histones
  • Schizosaccharomyces pombe Proteins
  • Heterochromatin
  • Histone-Lysine N-Methyltransferase
  • Cell Cycle Proteins
  • Methyltransferases
  • clr4 protein, S pombe