SET domains and histone methylation

Curr Opin Struct Biol. 2003 Dec;13(6):699-705. doi: 10.1016/


The realisation that SET domains, which are found in numerous proteins involved in chromatin regulation, catalyse the methylation of lysine residues has led to intense interest in their cellular, biochemical and structural properties. The structures of five SET domain proteins have been reported over the past year. SET domains possess a novel fold, and use adjacent domains for both structural stabilisation and the completion of their active sites. The cofactor S-adenosyl-L-methionine and peptide substrates bind on opposite faces of the SET domain. Remarkably, the sidechain of the target lysine approaches the transferred methyl group through a narrow channel that passes through the middle of the domain.

Publication types

  • Review

MeSH terms

  • Binding Sites
  • Catalysis
  • Chromosomal Proteins, Non-Histone
  • DNA / chemistry*
  • DNA / metabolism
  • DNA Methylation
  • Enzyme Activation
  • Histones / chemistry*
  • Methylation
  • Models, Molecular*
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / metabolism
  • Substrate Specificity
  • Transcription Factors


  • Chromosomal Proteins, Non-Histone
  • Histones
  • Proteins
  • Transcription Factors
  • DNA