title: Elaboration, diversification and regulation of the Sir1 family of silencing proteins in Saccharomyces.
abstract: Heterochromatin renders domains of chromosomes transcriptionally silent and, due to clonal variation in its formation, can generate heritably distinct populations of genetically identical cells. Saccharomyces cerevisiae's Sir1 functions primarily in the establishment, but not the maintenance, of heterochromatic silencing at the HMR and HML loci. In several Saccharomyces species, we discovered multiple paralogs of Sir1, called Kos1-Kos4 (Kin of Sir1). The Kos and Sir1 proteins contributed partially overlapping functions to silencing of both cryptic mating loci in S. bayanus. Mutants of these paralogs reduced silencing at HML more than at HMR. Most genes of the SIR1 family were located near telomeres, and at least one paralog was regulated by telomere position effect. In S. cerevisiae, Sir1 is recruited to the silencers at HML and HMR via its ORC interacting region (OIR), which binds the bromo adjacent homology (BAH) domain of Orc1. Zygosaccharomyces rouxii, which diverged from Saccharomyces after the appearance of the silent mating cassettes, but before the whole-genome duplication, contained an ortholog of Kos3 that was apparently the archetypal member of the family, with only one OIR. In contrast, a duplication of this domain was present in all orthologs of Sir1, Kos1, Kos2, and Kos4. We propose that the functional specialization of Sir3, itself a paralog of Orc1, as a silencing protein was facilitated by the tandem duplication of the OIR domain in the Sir1 family, allowing distinct Sir1-Sir3 and Sir1-Orc1 interactions through OIR-BAH domain interactions.
authors.affiliation: Department of Molecular and Cell Biology, California Institute of Quantitative Biosciences, University of California, Berkeley, CA 94720-3220, USA.
authors.forename: Jennifer E G
authors.initials: JE
authors.lastname: Gallagher
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Babiarz
authors.forename: Leonid
authors.initials: L
authors.lastname: Teytelman
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Wolfe
authors.forename: Jasper
authors.initials: J
authors.lastname: Rine
mesh_terms: D000595:Amino Acid Sequence; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D005816:Genetic Complementation Test; D014644:Genetic Variation / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D051738:Origin Recognition Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: C497214:ORC1 protein, S cerevisiae; D051738:Origin Recognition Complex; C084121:SIR1 protein, S cerevisiae; C084122:SIR3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae