Allosteric regulation of histone lysine methyltransferases: from context-specific regulation to selective drugs

Biochem Soc Trans. 2021 Apr 30;49(2):591-607. doi: 10.1042/BST20200238.


Histone lysine methyltransferases (HKMTs) are key regulators of many cellular processes. By definition, HKMTs catalyse the methylation of lysine residues in histone proteins. The enzymatic activities of HKMTs are under precise control, with their allosteric regulation emerging as a prevalent paradigm. We review the molecular mechanisms of allosteric regulation of HKMTs using well-studied histone H3 (K4, K9, K27 and K36) methyltransferases as examples. We discuss the current advances and future potential in targeting allosteric sites of HKMTs for drug development.

Keywords: allosteric regulation; histone lysine methyltransferases; set domain.

Publication types

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

MeSH terms

  • Allosteric Regulation / drug effects*
  • Drug Development / methods
  • Histone-Lysine N-Methyltransferase / chemistry
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / chemistry
  • Histones / metabolism*
  • Humans
  • Lysine / chemistry
  • Lysine / metabolism*
  • Methylation / drug effects
  • Pharmaceutical Preparations / administration & dosage*
  • Protein Binding / drug effects
  • Protein Conformation / drug effects
  • Protein Subunits / chemistry
  • Protein Subunits / genetics
  • Protein Subunits / metabolism


  • Histones
  • Pharmaceutical Preparations
  • Protein Subunits
  • Histone-Lysine N-Methyltransferase
  • Lysine