The genomic silencing of position-effect variegation in Drosophila melanogaster: interaction between the heterochromatin-associated proteins Su(var)3-7 and HP1

Position-effect variegation results from mosaic silencing by chromosomal re arrangements juxtaposing euchromatin genes next to pericentric heterochroma tin. An increase in the amounts of the heterochromatin-associated Su(var)3- 7 and HPI proteins augments silencing. Using the yeast two-hybrid protein i nteraction trap system, we have isolated HP1 using Su(var)3-7 as a bait, We have then delimited three binding sites on Su(var)3-7 for HP1, On HP1, the C-terminal moiety, including the chrome shadow domain, is required for int eraction. In vivo, both proteins co-localise not only in heterochromatin, b ut also in a limited set of sites in euchromatin and at telomeres. When del ocalised to the sites bound by the protein Polycomb in euchromatin, HP1 rec ruits Su(var)3-7. Finally, and in contrast with euchromatin genes, a decrea se in the amounts of both proteins enhances variegation of the light gene, one of the few genetic loci mapped within pericentric heterochromatin. This body of data supports a direct link between Su(var)3-7 and HPI in the geno mic silencing of position-effect variegation.