The HP1 chromo shadow domain binds a consensus peptide pentamer

Heterochromatin-associated protein 1 (HP1) [1] is thought to affect chromat in structure through interactions with other proteins in heterochromatin [2 ], Chrome domains located near the amino (amino chrome) and carboxy (chromo shadow) termini of HP1 may mediate such interactions, as suggested by doma in swapping, in vitro binding and 3D structural studies [3-8], Several HP1- associated proteins have been reported, providing candidates that might spe cifically complex with the chrome domains of HP1, However, such association studies provide little mechanistic insight and explore only a limited set of potential interactions in a largely non-competitive setting. To determin e how chrome domains can selectively interact with other proteins, we probe d random peptide phage display libraries using chrome domains from HP1, Our results demonstrate that a consensus pentapeptide is sufficient for specif ic interaction with the HP1 chrome shadow domain. The pentapeptide is found in the amino acid sequence of reported HP1-associated proteins, including the shadow domain itself, Peptides that bind the shadow domain also disrupt shadow domain dimers, Our results suggest that HP1 dimerization, which is thought to mediate heterochromatin compaction and cohesion, occurs via pent apeptide binding. In general, chrome domains may function by avidly binding short peptides at the surface of chromatin-associated proteins.