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PMID: 15545655 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Conserved locus-specific silencing functions of Schizosaccharomyces pombe sir2+.

Genetics ·Vol. 169 ·No. 3 ·2005-03-00 ·Pages 1243-60

Freeman-Cook LL, Gómez EB, Spedale EJ, Marlett J, Forsburg SL, Pillus L, Laurenson P

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.

MeSH Terms
Alternative Splicing Amino Acid Sequence Base Sequence Chromatin/genetics Conserved Sequence DNA Primers Exons Gene Expression Regulation, Fungal Gene Silencing Genes, Fungal Genes, Mating Type, Fungal Genes, Reporter Green Fluorescent Proteins/genetics Molecular Sequence Data Polymerase Chain Reaction Schizosaccharomyces/genetics Schizosaccharomyces pombe Proteins/genetics Sequence Alignment Sequence Homology, Amino Acid Sirtuins/genetics Transfection
Chemicals
Chromatin DNA Primers Schizosaccharomyces pombe Proteins Green Fluorescent Proteins Sirtuins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Freeman-Cook Lisa L
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
Gómez Eliana B
Spedale Erik J
Marlett John
Forsburg Susan L
Pillus Lorraine
Laurenson Patricia
References (94)
94 references, click to expand
  1. Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state.
    Mol Cell. 2003 Jul;12(1):51-62 PMID: 12887892
  2. The chromodomain protein Swi6: a key component at fission yeast centromeres.
    Science. 1995 Sep 8;269(5229):1429-31 PMID: 7660126
  3. Pcp1p, an Spc110p-related calmodulin target at the centrosome of the fission yeast Schizosaccharomyces pombe.
    Cell Growth Differ. 2002 Feb;13(2):47-58 PMID: 11864908
  4. Determining centromere identity: cyclical stories and forking paths.
    Nat Rev Genet. 2001 Aug;2(8):584-96 PMID: 11483983
  5. Drosophila Sir2 is required for heterochromatic silencing and by euchromatic Hairy/E(Spl) bHLH repressors in segmentation and sex determination.
    Cell. 2002 May 17;109(4):447-58 PMID: 12086602
  6. Mutations in Saccharomyces cerevisiae gene SIR2 can have differential effects on in vivo silencing phenotypes and in vitro histone deacetylation activity.
    Mol Biol Cell. 2002 Apr;13(4):1427-38 PMID: 11950950
  7. Localization of Sir2p: the nucleolus as a compartment for silent information regulators.
    EMBO J. 1997 Jun 2;16(11):3243-55 PMID: 9214640
  8. Stable inheritance of telomere chromatin structure and function in the absence of telomeric repeats.
    Genes Dev. 2003 Sep 15;17(18):2271-82 PMID: 12952894
  9. Analysis of Sir2p domains required for rDNA and telomeric silencing in Saccharomyces cerevisiae.
    Genetics. 2000 Mar;154(3):1069-83 PMID: 10757754
  10. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase.
    Science. 2004 Mar 26;303(5666):2011-5 PMID: 14976264
  11. Locus specificity determinants in the multifunctional yeast silencing protein Sir2.
    EMBO J. 2000 Jun 1;19(11):2641-51 PMID: 10835361
  12. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly.
    Science. 2001 Apr 6;292(5514):110-3 PMID: 11283354
  13. A Drosophila homologue of Sir2 modifies position-effect variegation but does not affect life span.
    Genetics. 2002 Dec;162(4):1675-85 PMID: 12524341
  14. HP1: facts, open questions, and speculation.
    J Struct Biol. 2002 Oct-Dec;140(1-3):10-6 PMID: 12490149
  15. The Schizosaccharomyces pombe hst4(+) gene is a SIR2 homologue with silencing and centromeric functions.
    Mol Biol Cell. 1999 Oct;10(10):3171-86 PMID: 10512858
  16. Mutations in rik1, clr2, clr3 and clr4 genes asymmetrically derepress the silent mating-type loci in fission yeast.
    Genetics. 1994 Jan;136(1):53-64 PMID: 8138176
  17. spRap1 and spRif1, recruited to telomeres by Taz1, are essential for telomere function in fission yeast.
    Curr Biol. 2001 Oct 16;11(20):1624-30 PMID: 11676925
  18. Modifiers of position effect are shared between telomeric and silent mating-type loci in S. cerevisiae.
    Cell. 1991 Sep 20;66(6):1279-87 PMID: 1913809
  19. Sum1 and Hst1 repress middle sporulation-specific gene expression during mitosis in Saccharomyces cerevisiae.
    EMBO J. 1999 Nov 15;18(22):6448-54 PMID: 10562556
  20. Mammalian SIRT1 represses forkhead transcription factors.
    Cell. 2004 Feb 20;116(4):551-63 PMID: 14980222
  21. Cell cycle-dependent specific positioning and clustering of centromeres and telomeres in fission yeast.
    J Cell Biol. 1993 Jun;121(5):961-76 PMID: 8388878
  22. RNAi extends its reach.
    Science. 2003 Aug 22;301(5636):1060-1 PMID: 12934001
  23. HP1 and the dynamics of heterochromatin maintenance.
    Nat Rev Mol Cell Biol. 2004 Apr;5(4):296-304 PMID: 15071554
  24. RNAi hushes heterochromatin.
    Genome Biol. 2002;3(12):REVIEWS1035 PMID: 12537580
  25. Transcriptional silencing in fission yeast.
    J Cell Physiol. 2000 Sep;184(3):311-8 PMID: 10911361
  26. The RITS complex-A direct link between small RNA and heterochromatin.
    Mol Cell. 2004 Feb 13;13(3):304-5 PMID: 14967138
  27. Pch2 links chromatin silencing to meiotic checkpoint control.
    Cell. 1999 Apr 30;97(3):313-24 PMID: 10319812
  28. The interaction of Alba, a conserved archaeal chromatin protein, with Sir2 and its regulation by acetylation.
    Science. 2002 Apr 5;296(5565):148-51 PMID: 11935028
  29. A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNA.
    Cell. 1989 Mar 10;56(5):771-6 PMID: 2647300
  30. Negative control of p53 by Sir2alpha promotes cell survival under stress.
    Cell. 2001 Oct 19;107(2):137-48 PMID: 11672522
  31. Establishment and maintenance of a heterochromatin domain.
    Science. 2002 Sep 27;297(5590):2232-7 PMID: 12215653
  32. Genetics and the specificity of the aging process.
    Science. 2003 Feb 28;299(5611):1351-4 PMID: 12610295
  33. Regulation of chromatin structure by site-specific histone H3 methyltransferases.
    Nature. 2000 Aug 10;406(6796):593-9 PMID: 10949293
  34. Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast.
    Nat Cell Biol. 2002 Jan;4(1):89-93 PMID: 11780129
  35. Centromere domain organization and histone modifications.
    Braz J Med Biol Res. 2002 May;35(5):499-507 PMID: 12011934
  36. Telomere-associated chromosome breakage in fission yeast results in variegated expression of adjacent genes.
    EMBO J. 1994 Aug 15;13(16):3801-11 PMID: 8070408
  37. Telomeric and rDNA silencing in Saccharomyces cerevisiae are dependent on a nuclear NAD(+) salvage pathway.
    Genetics. 2002 Mar;160(3):877-89 PMID: 11901108
  38. Requirement of heterochromatin for cohesion at centromeres.
    Science. 2001 Dec 21;294(5551):2539-42 PMID: 11598266
  39. Genetic and epigenetic regulation of the FLO gene family generates cell-surface variation in yeast.
    Cell. 2004 Feb 6;116(3):405-15 PMID: 15016375
  40. Single-molecule analysis reveals clustering and epigenetic regulation of replication origins at the yeast rDNA locus.
    Genes Dev. 2002 Oct 1;16(19):2479-84 PMID: 12368258
  41. Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae.
    Genetics. 1987 May;116(1):9-22 PMID: 3297920
  42. Longevity regulation in Saccharomyces cerevisiae: linking metabolism, genome stability, and heterochromatin.
    Microbiol Mol Biol Rev. 2003 Sep;67(3):376-99, table of contents PMID: 12966141
  43. Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe.
    Yeast. 1998 Jul;14(10):943-51 PMID: 9717240
  44. Binary switches and modification cassettes in histone biology and beyond.
    Nature. 2003 Oct 2;425(6957):475-9 PMID: 14523437
  45. Fission yeast Rap1 homolog is a telomere-specific silencing factor and interacts with Taz1p.
    Mol Cells. 2002 Apr 30;13(2):327-33 PMID: 12018857
  46. Centromere silencing and function in fission yeast is governed by the amino terminus of histone H3.
    Curr Biol. 2003 Oct 14;13(20):1748-57 PMID: 14561399
  47. Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence.
    EMBO J. 2002 May 15;21(10):2383-96 PMID: 12006491
  48. NAD+-dependent deacetylase Hst1p controls biosynthesis and cellular NAD+ levels in Saccharomyces cerevisiae.
    Mol Cell Biol. 2003 Oct;23(19):7044-54 PMID: 12972620
  49. Gene silencing: two faces of SIR2.
    Curr Biol. 2000 Oct 5;10(19):R708-11 PMID: 11050406
  50. Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine.
    Science. 2002 Dec 20;298(5602):2390-2 PMID: 12493915
  51. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase.
    Cell. 2001 Oct 19;107(2):149-59 PMID: 11672523
  52. nmt1 of fission yeast. A highly transcribed gene completely repressed by thiamine.
    J Biol Chem. 1990 Jul 5;265(19):10857-64 PMID: 2358444
  53. Heterochromatin and epigenetic control of gene expression.
    Science. 2003 Aug 8;301(5634):798-802 PMID: 12907790
  54. Four mating-type genes control sexual differentiation in the fission yeast.
    EMBO J. 1988 May;7(5):1537-47 PMID: 2900761
  55. HST1, a new member of the SIR2 family of genes.
    Yeast. 1996 Jun 15;12(7):631-40 PMID: 8810037
  56. Histone deacetylase homologs regulate epigenetic inheritance of transcriptional silencing and chromosome segregation in fission yeast.
    Genetics. 1998 Oct;150(2):563-76 PMID: 9755190
  57. Diversity in the Sir2 family of protein deacetylases.
    J Leukoc Biol. 2004 Jun;75(6):939-50 PMID: 14742637
  58. Transcriptional silencing in Saccharomyces cerevisiae and Schizosaccharomyces pombe.
    Nucleic Acids Res. 2002 Apr 1;30(7):1465-82 PMID: 11917007
  59. Telomere binding of the Rap1 protein is required for meiosis in fission yeast.
    Curr Biol. 2001 Oct 16;11(20):1618-23 PMID: 11676924
  60. Linking chromatin function with metabolic networks: Sir2 family of NAD(+)-dependent deacetylases.
    Trends Biochem Sci. 2003 Jan;28(1):41-8 PMID: 12517451
  61. Defective meiosis in telomere-silencing mutants of Schizosaccharomyces pombe.
    Nature. 1998 Apr 23;392(6678):825-8 PMID: 9572142
  62. Sir2 links chromatin silencing, metabolism, and aging.
    Genes Dev. 2000 May 1;14(9):1021-6 PMID: 10809662
  63. Mutations in the fission yeast silencing factors clr4+ and rik1+ disrupt the localisation of the chromo domain protein Swi6p and impair centromere function.
    J Cell Sci. 1996 Nov;109 ( Pt 11):2637-48 PMID: 8937982
  64. The Sir2 protein family: A novel deacetylase for gene silencing and more.
    Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14030-2 PMID: 11114164
  65. Tethering of HP1 proteins to chromatin is relieved by phosphoacetylation of histone H3.
    EMBO Rep. 2004 May;5(5):490-6 PMID: 15105826
  66. A cytosolic NAD-dependent deacetylase, Hst2p, can modulate nucleolar and telomeric silencing in yeast.
    EMBO J. 2001 Jan 15;20(1-2):197-209 PMID: 11226170
  67. The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stability.
    Genes Dev. 1995 Dec 1;9(23):2888-902 PMID: 7498786
  68. Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast.
    Genes Dev. 1997 Jan 15;11(2):255-69 PMID: 9009207
  69. Distinct protein interaction domains and protein spreading in a complex centromere.
    Genes Dev. 2000 Apr 1;14(7):783-91 PMID: 10766735
  70. Position effect variegation at fission yeast centromeres.
    Cell. 1994 Jan 14;76(1):157-69 PMID: 8287474
  71. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases.
    Proc Natl Acad Sci U S A. 2000 May 23;97(11):5807-11 PMID: 10811920
  72. A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family.
    Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6658-63 PMID: 10841563
  73. Heterochromatin: new possibilities for the inheritance of structure.
    Curr Opin Genet Dev. 2002 Apr;12(2):178-87 PMID: 11893491
  74. Different phenotypes in vivo are associated with ATPase motif mutations in Schizosaccharomyces pombe minichromosome maintenance proteins.
    Genetics. 2002 Apr;160(4):1305-18 PMID: 11973289
  75. Hyperactivation of the silencing proteins, Sir2p and Sir3p, causes chromosome loss.
    Genetics. 1997 Mar;145(3):605-14 PMID: 9055071
  76. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase.
    Mol Cell. 2003 Feb;11(2):437-44 PMID: 12620231
  77. In vivo dynamics of Swi6 in yeast: evidence for a stochastic model of heterochromatin.
    Mol Cell Biol. 2004 Apr;24(8):3157-67 PMID: 15060140
  78. The genome sequence of Schizosaccharomyces pombe.
    Nature. 2002 Feb 21;415(6874):871-80 PMID: 11859360
  79. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe.
    Methods Enzymol. 1991;194:795-823 PMID: 2005825
  80. The Drosophila melanogaster sir2+ gene is nonessential and has only minor effects on position-effect variegation.
    Genetics. 2003 Mar;163(3):931-7 PMID: 12663533
  81. A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance.
    Mol Gen Genet. 1984;197(2):345-6 PMID: 6394957
  82. Regulation of telomere length and function by a Myb-domain protein in fission yeast.
    Nature. 1997 Feb 20;385(6618):744-7 PMID: 9034194
  83. The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae.
    Annu Rev Biochem. 2003;72:481-516 PMID: 12676793
  84. Acetylation of TAF(I)68, a subunit of TIF-IB/SL1, activates RNA polymerase I transcription.
    EMBO J. 2001 Mar 15;20(6):1353-62 PMID: 11250901
  85. MAR1-a Regulator of the HMa and HMalpha Loci in SACCHAROMYCES CEREVISIAE.
    Genetics. 1979 Sep;93(1):37-50 PMID: 17248968
  86. A unique class of conditional sir2 mutants displays distinct silencing defects in Saccharomyces cerevisiae.
    Genetics. 2002 Oct;162(2):721-36 PMID: 12399383
  87. Sir2 regulates histone H3 lysine 9 methylation and heterochromatin assembly in fission yeast.
    Curr Biol. 2003 Jul 15;13(14):1240-6 PMID: 12867036
  88. Mutations derepressing silent centromeric domains in fission yeast disrupt chromosome segregation.
    Genes Dev. 1995 Jan 15;9(2):218-33 PMID: 7851795
  89. Three additional linkage groups that repress transcription and meiotic recombination in the mating-type region of Schizosaccharomyces pombe.
    Genetics. 1994 Sep;138(1):29-38 PMID: 8001791
  90. RNAi-mediated targeting of heterochromatin by the RITS complex.
    Science. 2004 Jan 30;303(5658):672-6 PMID: 14704433
  91. An unusual form of transcriptional silencing in yeast ribosomal DNA.
    Genes Dev. 1997 Jan 15;11(2):241-54 PMID: 9009206
  92. Histone gene deficiencies and position--effect variegation in Drosophila.
    Nature. 1979 Nov 15;282(5736):312-4 PMID: 116133
  93. The clr1 locus regulates the expression of the cryptic mating-type loci of fission yeast.
    Genetics. 1992 Jun;131(2):287-96 PMID: 1644273
  94. High efficiency transformation of intact yeast cells using single stranded nucleic acids as a carrier.
    Curr Genet. 1989 Dec;16(5-6):339-46 PMID: 2692852
Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
Published
2005-03-00
Epub
2004-00-15
Pages
1243-60
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1449530
Subset
IM
Grants
NIGMS NIH HHS · R01 GM059321-05A1 · United States
NIGMS NIH HHS · R01 GM059321 · United States
NIGMS NIH HHS · R01 GM054778 · United States
NIGMS NIH HHS · GM54778 · United States
NIGMS NIH HHS · GM59321 · United States
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