The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules

Nat Struct Mol Biol. 2008 Mar;15(3):245-50. doi: 10.1038/nsmb.1384. Epub 2008 Feb 10.

Abstract

Histone modifications have important roles in transcriptional control, mitosis and heterochromatin formation. G9a and G9a-like protein (GLP) are euchromatin-associated methyltransferases that repress transcription by mono- and dimethylating histone H3 at Lys9 (H3K9). Here we demonstrate that the ankyrin repeat domains of G9a and GLP bind with strong preference to N-terminal H3 peptides containing mono- or dimethyl K9. X-ray crystallography revealed the basis for recognition of the methylated lysine by a partial hydrophobic cage with three tryptophans and one acidic residue. Substitution of key residues in the cage eliminated the H3 tail interaction. Hence, G9a and GLP contain a new type of methyllysine binding module (the ankyrin repeat domains) and are the first examples of protein (histone) methyltransferases harboring in a single polypeptide the activities that generate and read the same epigenetic mark.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Ankyrin Repeat*
  • COS Cells
  • Chlorocebus aethiops
  • Histone-Lysine N-Methyltransferase / chemistry*
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / metabolism
  • Humans
  • Lysine / metabolism*
  • Methylation
  • Methyltransferases / chemistry*
  • Methyltransferases / metabolism
  • Mice
  • Mutant Proteins / chemistry
  • Mutant Proteins / metabolism
  • Mutation / genetics
  • Peptides / metabolism
  • Protein Binding

Substances

  • Histones
  • Mutant Proteins
  • Peptides
  • EHMT1 protein, human
  • Methyltransferases
  • G9a protein, mouse
  • Histone-Lysine N-Methyltransferase
  • Lysine

Associated data

  • PDB/3B7B
  • PDB/3B95