Heterochromatin protein-1 (HP1) is a methyl-lysine binding protein localized at heterochromatin sites, where it mediates gene silencing. It has been shown that mammalian methyltransferases that selectively methylate histone H3 on lysine-9 generate a binding site for HP1 proteins, a family of heterochromatic adaptor molecules implicated in both gene silencing and supranucleosomal chromatin structure. High-affinity in vitro recognition of a methylated histone H3 peptide by HP1 requires a functional chromodomain. Thus, the HP1 chromodomain 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 reintroduction of a catalytically active SUV39H1 HMTase.
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