Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains

摘要: On the histone H3 tail, Lys 9 and 27 are both methylation sites associated with epigenetic repression, reside within a highly related sequence motif ARKS. Here we show that chromodomain proteins Polycomb (Pc) HP1 (heterochromatin protein 1) discriminatory for binding to these in vivo vitro. In Drosophila S2 cells, on polytene chromosomes, methyl-Lys Pc excluded from areas enriched HP1. Swapping of regions is sufficient switching nuclear localization patterns factors, indicating role their chromodomains target site discrimination. To better understand molecular basis selection methyl-lysine sites, solved 1.8 A structure complex peptide bearing trimethyl-Lys 27, compared it our previously determined 9. The distinguishes its tail via an extended recognition groove binds five additional residues preceding ARKS motif.