Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins

Distinct modifications of histone amino termini, such as acetylation, phosphorylation and methylation, have been proposed to underlie a chromatin-based regulatory mechanism 1 , 2 that modulates the accessibility of genetic information. In addition to histone modifications that facilitate gene activity, it is of similar importance to restrict inappropriate gene expression 3 , 4 if cellular and developmental programmes are to proceed unperturbed. Here we show that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases) 5 generate a binding site for HP1 proteins—a family of heterochromatic adaptor molecules 6 , 7 implicated in both gene silencing and supra-nucleosomal chromatin structure. High-affinity in vitro recognition of a methylated histone H3 peptide by HP1 requires a functional chromo domain; thus, the HP1 chromo domain is a specific interaction motif for the methyl epitope on lysine 9 of histone H3. In vivo , heterochromatin association of HP1 proteins is lost in Suv39h double-null primary mouse fibroblasts but is restored after the re-introduction of a catalytically active SUV39H1 HMTase. Our data define a molecular mechanism through which the SUV39H–HP1 methylation system can contribute to the propagation of heterochromatic subdomains in native chromatin.