title: Conserved locus-specific silencing functions of Schizosaccharomyces pombe sir2+.
abstract: In Schizosaccharomyces pombe, three genes, sir2(+), hst2(+), and hst4(+), encode members of the Sir2 family of conserved NAD(+)-dependent protein deacetylases. The S. pombe sir2(+) gene encodes a nuclear protein that is not essential for viability or for resistance to treatment with UV or a microtubule-destabilizing agent. However, sir2(+) is essential for full transcriptional silencing of centromeres, telomeres, and the cryptic mating-type loci. Chromatin immunoprecipitation results suggest that the Sir2 protein acts directly at these chromosomal regions. Enrichment of Sir2p at silenced regions does not require the HP1 homolog Swi6p; instead, Swi6-GFP localization to telomeres depends in part on Sir2p. The phenotype of sir2 swi6 double mutants supports a model whereby Sir2p functions prior to Swi6p at telomeres and the silent mating-type loci. However, Sir2p does not appear to be essential for the localization of Swi6p to centromeric foci. Cross-complementation experiments showed that the Saccharomyces cerevisiae SIR2 gene can function in place of S. pombe sir2(+), suggesting overlapping deacetylation substrates in both species. These results also suggest that, despite differences in most of the other molecules required, the two distantly related yeast species share a mechanism for targeting Sir2p homologs to silent chromatin.
authors.affiliation: Division of Biological Sciences, Section of Molecular Biology and UCSD Center for Cancer Research, University of California, San Diego, 92093-0347, USA. lpillus@biomail.ucsd.edu
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Freeman-Cook
authors.forename: Eliana B
authors.initials: EB
authors.lastname: Gómez
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Spedale
authors.forename: John
authors.initials: J
authors.lastname: Marlett
authors.forename: Susan L
authors.initials: SL
authors.lastname: Forsburg
authors.forename: Lorraine
authors.initials: L
authors.lastname: Pillus
authors.forename: Patricia
authors.initials: P
authors.lastname: Laurenson
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002843:Chromatin / Q000235:genetics; D017124:Conserved Sequence; D017931:DNA Primers; D005091:Exons; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D005800:Genes, Fungal; D049770:Genes, Mating Type, Fungal; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D037761:Sirtuins / Q000235:genetics*; D014162:Transfection
chemical_list: D002843:Chromatin; D017931:DNA Primers; D029702:Schizosaccharomyces pombe Proteins; D049452:Green Fluorescent Proteins; D037761:Sirtuins