Mechanistic and structural studies of KDM-catalysed demethylation of histone 1 isotype 4 at lysine 26

FEBS Lett. 2018 Oct;592(19):3264-3273. doi: 10.1002/1873-3468.13231. Epub 2018 Sep 14.


N-Methylation of lysyl residues is widely observed on histone proteins. Using isolated enzymes, we report mechanistic and structural studies on histone lysine demethylase (KDM)-catalysed demethylation of Nε -methylated lysine 26 on histone 1 isotype 4 (H1.4). The results reveal that methylated H1.4K26 is a substrate for all members of the KDM4 subfamily and that KDM4A-catalysed demethylation of H1.4K26me3 peptide is similarly efficient to that of H3K9me3. Crystallographic studies of an H1.4K26me3:KDM4A complex reveal a conserved binding geometry to that of H3K9me3. In the light of the high activity of the KDM4s on this mark, our results suggest JmjC KDM-catalysed demethylation of H1.4K26 may be as prevalent as demethylation on the H3 tail and warrants further investigation in cells.

Keywords: 2-oxoglutarate oxygenases; JmjC demethylases; demethylases; epigenetics; histones; lysine N-methylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biocatalysis
  • Crystallography, X-Ray
  • Demethylation*
  • Histones / chemistry
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / chemistry
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Kinetics
  • Lysine / chemistry
  • Lysine / genetics
  • Lysine / metabolism*
  • Protein Binding
  • Protein Conformation
  • Sequence Homology, Amino Acid


  • Histones
  • Jumonji Domain-Containing Histone Demethylases
  • KDM4A protein, human
  • Lysine