Targeting of the yeast Ty5 retrotransposon to silent chromatin is mediatedby interactions between integrase and Sir4p

The Ty5 retrotransposons of Saccharomyces cerevisiae integrate preferential ly into regions of silent chromatin at the telomeres and silent mating loci (HAIR and HAIL). We define a Ty5-encoded targeting domain that spans 6 ami no acid residues near the C terminus of integrase (LXSSXP). The targeting d omain establishes silent chromatin when it is tethered to a weakened HAIR-E silencer, and it disrupts telomeric silencing when it is overexpressed. As determined by both yeast two-hybrid and in vitro binding assays, the targe ting domain interacts with the C terminus of Sir4p, a structural component of silent chromatin. This interaction is abrogated by mutations in the targ eting domain that disrupt integration into silent chromatin, suggesting tha t recognition of Sir4p by the targeting domain is the primary determinant i n Ty5 target specificity.