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Genetics. 1997 Apr; 145(4): 923–934.
PMCID: PMC1207897

The Role of Sas2, an Acetyltransferase Homologue of Saccharomyces Cerevisiae, in Silencing and Orc Function

Abstract

Silencing at the cryptic mating-type loci HML and HMR of Saccharomyces cerevisiae requires regulatory sites called silencers. Mutations in the Rap1 and Abf1 binding sites of the HMR-E silencer (HMRa-e**) cause the silencer to be nonfunctional, and hence, cause derepression of HMR. Here, we have isolated and characterized mutations in SAS2 as second-site suppressors of the silencing defect of HMRa-e**. Silencing conferred by the removal of SAS2 (sas2Δ) depended upon the integrity of the ARS consensus sequence of the HMR-E silencer, thus arguing for an involvement of the origin recognition complex (ORC). Restoration of silencing by sas2Δ required ORC2 and ORC5, but not SIR1 or RAP1. Furthermore, sas2Δ suppressed the temperature sensitivity, but not the silencing defect of orc2-1 and orc5-1. Moreover, sas2Δ had opposing effects on silencing of HML and HMR. The putative Sas2 protein bears similarities to known protein acetyltransferases. Several models for the role of Sas2 in silencing are discussed.

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Selected References

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  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. [PubMed]
  • Axelrod A, Rine J. A role for CDC7 in repression of transcription at the silent mating-type locus HMR in Saccharomyces cerevisiae. Mol Cell Biol. 1991 Feb;11(2):1080–1091. [PMC free article] [PubMed]
  • Ayyagari R, Impellizzeri KJ, Yoder BL, Gary SL, Burgers PM. A mutational analysis of the yeast proliferating cell nuclear antigen indicates distinct roles in DNA replication and DNA repair. Mol Cell Biol. 1995 Aug;15(8):4420–4429. [PMC free article] [PubMed]
  • Bell SP, Kobayashi R, Stillman B. Yeast origin recognition complex functions in transcription silencing and DNA replication. Science. 1993 Dec 17;262(5141):1844–1849. [PubMed]
  • Blackburn EH. Telomeres: no end in sight. Cell. 1994 Jun 3;77(5):621–623. [PubMed]
  • Brand AH, Micklem G, Nasmyth K. A yeast silencer contains sequences that can promote autonomous plasmid replication and transcriptional activation. Cell. 1987 Dec 4;51(5):709–719. [PubMed]
  • Braunstein M, Rose AB, Holmes SG, Allis CD, Broach JR. Transcriptional silencing in yeast is associated with reduced nucleosome acetylation. Genes Dev. 1993 Apr;7(4):592–604. [PubMed]
  • Brownell JE, Zhou J, Ranalli T, Kobayashi R, Edmondson DG, Roth SY, Allis CD. Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell. 1996 Mar 22;84(6):843–851. [PubMed]
  • Cullmann G, Fien K, Kobayashi R, Stillman B. Characterization of the five replication factor C genes of Saccharomyces cerevisiae. Mol Cell Biol. 1995 Sep;15(9):4661–4671. [PMC free article] [PubMed]
  • Foss M, McNally FJ, Laurenson P, Rine J. Origin recognition complex (ORC) in transcriptional silencing and DNA replication in S. cerevisiae. Science. 1993 Dec 17;262(5141):1838–1844. [PubMed]
  • Hearn MG, Hedrick A, Grigliatti TA, Wakimoto BT. The effect of modifiers of position-effect variegation on the variegation of heterochromatic genes of Drosophila melanogaster. Genetics. 1991 Aug;128(4):785–797. [PMC free article] [PubMed]
  • Jeppesen P, Turner BM. The inactive X chromosome in female mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic marker for gene expression. Cell. 1993 Jul 30;74(2):281–289. [PubMed]
  • Klar AJ, Kakar SN, Ivy JM, Hicks JB, Livi GP, Miglio LM. SUM1, an apparent positive regulator of the cryptic mating-type loci in Saccharomyces cerevisiae. Genetics. 1985 Dec;111(4):745–758. [PMC free article] [PubMed]
  • Klebe RJ, Harriss JV, Sharp ZD, Douglas MG. A general method for polyethylene-glycol-induced genetic transformation of bacteria and yeast. Gene. 1983 Nov;25(2-3):333–341. [PubMed]
  • Kleff S, Andrulis ED, Anderson CW, Sternglanz R. Identification of a gene encoding a yeast histone H4 acetyltransferase. J Biol Chem. 1995 Oct 20;270(42):24674–24677. [PubMed]
  • Laurenson P, Rine J. SUM1-1: a suppressor of silencing defects in Saccharomyces cerevisiae. Genetics. 1991 Nov;129(3):685–696. [PMC free article] [PubMed]
  • Le MH, Duricka D, Karpen GH. Islands of complex DNA are widespread in Drosophila centric heterochromatin. Genetics. 1995 Sep;141(1):283–303. [PMC free article] [PubMed]
  • Loo S, Rine J. Silencing and heritable domains of gene expression. Annu Rev Cell Dev Biol. 1995;11:519–548. [PubMed]
  • Loo S, Laurenson P, Foss M, Dillin A, Rine J. Roles of ABF1, NPL3, and YCL54 in silencing in Saccharomyces cerevisiae. Genetics. 1995 Nov;141(3):889–902. [PMC free article] [PubMed]
  • McNally FJ, Rine J. A synthetic silencer mediates SIR-dependent functions in Saccharomyces cerevisiae. Mol Cell Biol. 1991 Nov;11(11):5648–5659. [PMC free article] [PubMed]
  • Megee PC, Morgan BA, Mittman BA, Smith MM. Genetic analysis of histone H4: essential role of lysines subject to reversible acetylation. Science. 1990 Feb 16;247(4944):841–845. [PubMed]
  • Meijers JC, Chung DW. Organization of the gene coding for human protein C inhibitor (plasminogen activator inhibitor-3). Assignment of the gene to chromosome 14. J Biol Chem. 1991 Aug 15;266(23):15028–15034. [PubMed]
  • Mullen JR, Kayne PS, Moerschell RP, Tsunasawa S, Gribskov M, Colavito-Shepanski M, Grunstein M, Sherman F, Sternglanz R. Identification and characterization of genes and mutants for an N-terminal acetyltransferase from yeast. EMBO J. 1989 Jul;8(7):2067–2075. [PMC free article] [PubMed]
  • Müller J. Transcriptional silencing by the Polycomb protein in Drosophila embryos. EMBO J. 1995 Mar 15;14(6):1209–1220. [PMC free article] [PubMed]
  • Park EC, Szostak JW. Point mutations in the yeast histone H4 gene prevent silencing of the silent mating type locus HML. Mol Cell Biol. 1990 Sep;10(9):4932–4934. [PMC free article] [PubMed]
  • Patterson M, Sclafani RA, Fangman WL, Rosamond J. Molecular characterization of cell cycle gene CDC7 from Saccharomyces cerevisiae. Mol Cell Biol. 1986 May;6(5):1590–1598. [PMC free article] [PubMed]
  • Rastan S. X chromosome inactivation and the Xist gene. Curr Opin Genet Dev. 1994 Apr;4(2):292–297. [PubMed]
  • Reifsnyder C, Lowell J, Clarke A, Pillus L. Yeast SAS silencing genes and human genes associated with AML and HIV-1 Tat interactions are homologous with acetyltransferases. Nat Genet. 1996 Sep;14(1):42–49. [PubMed]
  • Reuter G, Dorn R, Hoffmann HJ. Butyrate sensitive suppressor of position-effect variegation mutations in Drosophila melanogaster. Mol Gen Genet. 1982;188(3):480–485. [PubMed]
  • Rose MD, Novick P, Thomas JH, Botstein D, Fink GR. A Saccharomyces cerevisiae genomic plasmid bank based on a centromere-containing shuttle vector. Gene. 1987;60(2-3):237–243. [PubMed]
  • Shaw WV, Leslie AG. Chloramphenicol acetyltransferase. Annu Rev Biophys Biophys Chem. 1991;20:363–386. [PubMed]
  • Sherman F. Getting started with yeast. Methods Enzymol. 1991;194:3–21. [PubMed]
  • Sikorski RS, Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. [PMC free article] [PubMed]
  • Spencer F, Gerring SL, Connelly C, Hieter P. Mitotic chromosome transmission fidelity mutants in Saccharomyces cerevisiae. Genetics. 1990 Feb;124(2):237–249. [PMC free article] [PubMed]
  • Sussel L, Vannier D, Shore D. Epigenetic switching of transcriptional states: cis- and trans-acting factors affecting establishment of silencing at the HMR locus in Saccharomyces cerevisiae. Mol Cell Biol. 1993 Jul;13(7):3919–3928. [PMC free article] [PubMed]
  • Taunton J, Hassig CA, Schreiber SL. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science. 1996 Apr 19;272(5260):408–411. [PubMed]
  • Tercero JC, Riles LE, Wickner RB. Localized mutagenesis and evidence for post-transcriptional regulation of MAK3. A putative N-acetyltransferase required for double-stranded RNA virus propagation in Saccharomyces cerevisiae. J Biol Chem. 1992 Oct 5;267(28):20270–20276. [PubMed]
  • Thomas BJ, Rothstein R. Elevated recombination rates in transcriptionally active DNA. Cell. 1989 Feb 24;56(4):619–630. [PubMed]
  • Thompson JS, Ling X, Grunstein M. Histone H3 amino terminus is required for telomeric and silent mating locus repression in yeast. Nature. 1994 May 19;369(6477):245–247. [PubMed]
  • Triolo T, Sternglanz R. Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing. Nature. 1996 May 16;381(6579):251–253. [PubMed]
  • Weiler KS, Wakimoto BT. Heterochromatin and gene expression in Drosophila. Annu Rev Genet. 1995;29:577–605. [PubMed]
  • Yoshikawa A, Isono S, Sheback A, Isono K. Cloning and nucleotide sequencing of the genes rimI and rimJ which encode enzymes acetylating ribosomal proteins S18 and S5 of Escherichia coli K12. Mol Gen Genet. 1987 Oct;209(3):481–488. [PubMed]

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