Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27.
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.
Min
Jinrong
J
W.M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Zhang
Yi
Y
Xu
Rui-Ming
RM
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
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