Progressive methylation of ageing histones by Dot1 functions as a timer

EMBO Rep. 2011 Sep 1;12(9):956-62. doi: 10.1038/embor.2011.131.


Post-translational modifications of histone proteins have a crucial role in regulating gene expression. If efficiently re-established after chromosome duplication, histone modifications could help propagate gene expression patterns in dividing cells by epigenetic mechanisms. We used an integrated approach to investigate the dynamics of the conserved methylation of histone H3 Lys 79 (H3K79) by Dot1. Our results show that methylation of H3K79 progressively changes after histone deposition, which is incompatible with a rapid copy mechanism. Instead, methylation accumulates on ageing histones, providing the cell with a timer mechanism to directly couple cell-cycle length to changes in chromatin modification on the nucleosome core.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Cell Cycle
  • Chromatin / metabolism
  • Gene Expression Regulation, Fungal
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / metabolism*
  • Methylation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nucleosomes
  • Protein Processing, Post-Translational
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*


  • Chromatin
  • Histones
  • Nuclear Proteins
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • Dot1 protein, S cerevisiae
  • Histone-Lysine N-Methyltransferase