FUNCTIONAL-ANALYSIS OF THE CHROMO DOMAIN OF HP1

Heterochromatin protein 1 (HP1) is a non-histone chromosomal protein i n Drosophila with dosage-dependent effects on heterochromatin-mediated gene silencing, An evolutionarily conserved amino acid sequence in th e N-terminal half of HP1 (the 'chromo domain') shares >60% sequence id entity with a motif found in the Polycomb protein, a silencer of homeo tic genes. We report here that point mutations in the HP1 chrome domai n abolish the ability of HP1 to promote gene silencing, We show that t he HP1 chrome domain, like the Polycomb chrome domain, has chromosome binding activity, but to distinct chromosomal sites. We constructed a chimeric HP1-Polycomb protein, consisting of the chrome domain of Poly comb in the context of HP1, and show that it binds to both heterochrom atin and Polycomb binding sites in polytene chromosomes, In flies expr essing chimeric HP1-Polycomb protein, endogenous HP1 is mislocalized t o Polycomb binding sites, and endogenous Polycomb is misdirected to th e heterochromatic chromocenter, suggesting that both proteins are recr uited to their distinct chromosomal binding sites through protein-prot ein contacts, Chimeric HP1-Polycomb protein expression in transgenic f lies promotes heterochromatin-mediated gene silencing, supporting the view that the chrome domain homology reflects a common mechanistic bas is for homeotic and heterochromatic silencing.