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.
