Conversion of a gene-specific repressor to a regional silencer.
In Saccharomyces cerevisiae, gene silencing at the HMR and HML loci is normally dependent on Sir2p, Sir3p, and Sir4p, which are structural components of silenced chromatin. Sir2p is a NAD+-dependent histone deacetylase required for silencing. Silencing can be restored in cells lacking Sir proteins by a dominant mutation in SUM1, which normally acts as a mitotic repressor of meiotic genes. This study found that mutant Sum1-1p, but not wild-type Sum1p, associated directly with HM loci. The origin recognition complex (ORC) was required for Sum1-1p-mediated silencing, and mutations in ORC genes reduced association of Sum1-1p with the HM 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 hypoacetylation of the nucleosomes at HM loci. Thus, Sum1-1p and Hst1p could substitute for Sir proteins to achieve silencing through formation of a compositionally distinct type of heterochromatin.
Rusché
L N
LN
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
Rine
J
J
D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics; D000939:Epitopes; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D005799:Genes, Dominant; D005838:Genotype; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D051738:Origin Recognition Complex; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D000939:Epitopes; D005656:Fungal Proteins; D006570:Heterochromatin; D006657:Histones; D009687:Nuclear Proteins; D051738:Origin Recognition Complex; D012097:Repressor Proteins; C100925:SUM1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D015534:Trans-Activators; D012313:RNA; C103934:HST1 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases