Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27

Genes Dev. 2003 Aug 1;17(15):1823-8. doi: 10.1101/gad.269603.

Abstract

The chromodomain of Drosophila Polycomb protein is essential for maintaining the silencing state of homeotic genes during development. Recent studies suggest that Polycomb mediates the assembly of repressive higher-order chromatin structures in conjunction with the methylation of Lys 27 of histone H3 by a Polycomb group repressor complex. A similar mechanism in heterochromatin assembly is mediated by HP1, a chromodomain protein that binds to histone H3 methylated at Lys 9. To understand the molecular mechanism of the methyl-Lys 27 histone code recognition, we have determined a 1.4-A-resolution structure of the chromodomain of Polycomb in complex with a histone H3 peptide trimethylated at Lys 27. The structure reveals a conserved mode of methyl-lysine binding and identifies Polycomb-specific interactions with histone H3. The structure also reveals a dPC dimer in the crystal lattice that is mediated by residues specifically conserved in the Polycomb family of chromodomains. The dimerization of dPC can effectively account for the histone-binding specificity and provides new mechanistic insights into the function of Polycomb. We propose that self-association is functionally important for Polycomb.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromatin / metabolism
  • Crystallography, X-Ray
  • Drosophila
  • Drosophila Proteins / metabolism*
  • Glutathione Transferase / metabolism
  • Heterochromatin / metabolism*
  • Histones / metabolism*
  • Lysine / chemistry
  • Lysine / metabolism
  • Methylation*
  • Models, Molecular
  • Molecular Sequence Data
  • Polycomb Repressive Complex 1
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid

Substances

  • Chromatin
  • Drosophila Proteins
  • Heterochromatin
  • Histones
  • Pc protein, Drosophila
  • Recombinant Fusion Proteins
  • Polycomb Repressive Complex 1
  • Glutathione Transferase
  • Lysine

Associated data

  • PDB/1PFB