title: Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27.
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.
authors.affiliation: W.M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Min
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rui-Ming
authors.initials: RM
authors.lastname: Xu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D018360:Crystallography, X-Ray; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D008745:Methylation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D063150:Polycomb Repressive Complex 1; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; D006570:Heterochromatin; D006657:Histones; C066770:Pc protein, Drosophila; D011993:Recombinant Fusion Proteins; D063150:Polycomb Repressive Complex 1; D005982:Glutathione Transferase; D008239:Lysine