Conversion of a gene-specific repressor to a regional silencer

In Saccharomyces cerevisiae, gene silencing at the HMR and HML loci is norm ally dependent on Sir2p, Sir3p, and Sir4p, which are structural components of silenced chromatin. Sir2p is a NAD+-dependent histone deacetylase requir ed for silencing. Silencing can be restored in cells lacking Sir proteins b y a dominant mutation in SUM1, which normally acts as a mitotic repressor o f meiotic genes. This study found that mutant Sum1-1p, but not wild-type Su m1p, associated directly with HM loci. The origin recognition complex (ORC) was required for Sum1-1p-mediated silencing, and mutations in ORC genes re duced association of Sum1-1p with the Hdl loci. Sum1-1p-mediated silencing also depended on HST1, a paralog of SIR2. Both Sum1-1p and wild-type Sum1p interacted with Hst1p in coimmunoprecipitation experiments. Therefore, the SUM1-1 mutation did not change the affinity of Sum1p for Hst1p, but rather relocalized Sum1p to the HM loci. Sum1-1-Hst1p action led to hypoacetylatio n of the nucleosomes at HM loci. Thus, Sum1-1p and Hst1p could substitute f or Sir proteins to achieve silencing through formation of a compositionally distinct type of heterochromatin.