Targeting of SIR1 protein establishes transcriptional silencing at HM loci and telomeres in yeast.

Previous studies suggest that the yeast SIR1 protein is involved in the establishment of transcriptional silencing at the HM mating-type loci. Here we show that a GAL4 DNA-binding domain-SIR1 hybrid protein (GBD-SIR1), when targeted to an HMR locus containing GAL4-binding sites (UASG), can establish silencing and bypass the requirement for the silencer element HMR-E. Silencing mediated by GBD-SIR1 requires the trans-acting factors that normally participate in repression, namely, SIR2, SIR3, SIR4, and histone H4. However, GBD hybrids with SIR2, SIR3, or SIR4 cannot establish silencing. Telomeric silencing, which does not require SIR1 and is normally unstable, is greatly improved by tethering GBD-SIR1 to the telomere. These experiments support a model in which native SIR1 protein is brought to the HM loci by proteins bound to the silencers. Telomeres appear to lack the ability to recruit SIR1, and that is why telomeric silencing is unstable.