Histone lysine methylation dynamics: establishment, regulation, and biological impact

Mol Cell. 2012 Nov 30;48(4):491-507. doi: 10.1016/j.molcel.2012.11.006.


Histone lysine methylation has emerged as a critical player in the regulation of gene expression, cell cycle, genome stability, and nuclear architecture. Over the past decade, a tremendous amount of progress has led to the characterization of methyl modifications and the lysine methyltransferases (KMTs) and lysine demethylases (KDMs) that regulate them. Here, we review the discovery and characterization of the KMTs and KDMs and the methyl modifications they regulate. We discuss the localization of the KMTs and KDMs as well as the distribution of lysine methylation throughout the genome. We highlight how these data have shaped our view of lysine methylation as a key determinant of complex chromatin states. Finally, we discuss the regulation of KMTs and KDMs by proteasomal degradation, posttranscriptional mechanisms, and metabolic status. We propose key questions for the field and highlight areas that we predict will yield exciting discoveries in the years to come.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Histone Demethylases / metabolism
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / chemistry
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Lysine / chemistry
  • Lysine / genetics
  • Lysine / metabolism*
  • Methylation


  • Histones
  • Histone Demethylases
  • Histone-Lysine N-Methyltransferase
  • Lysine