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Yeast SAS silencing genes and human genes associated with AML and HIV–1 Tat interactions are homologous with acetyltransferases

Nature Genetics volume 14, pages 42–49 (1996)Cite this article

An Erratum to this article was published on 01 May 1997

Abstract

Silencing is an epigenetic form of transcriptional regulation whereby genes are heritably, but not necessarily permanently, inactivated. We have identified the Saccharomyces cerevisiae genes SAS2 and SAS3 through a screen for enhancers of sir1 epigenetic silencing defects. SAS2, SAS3 and a Schizosaccharomyces pombe homologue are closely related to several human genes, including one associated with acute myeloid leukaemia arising from the recurrent translocation t(8;16)(p11;p13) and one implicated in HIV–1 Tat interactions. All of these genes encode proteins with an atypical zinc finger and well–conserved similarities to acetyltransferases. Sequence similarities and yeast mutant phenotypes suggest that SAS–like genes function in transcriptional regulation and cell–cycle exit and reveal novel connections between transcriptional silencing and human disease.

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References

  1. Bird, A.P. Gene number, noise reduction and biological complexity. Trends. Genet. 11, 94–100 (1995).

    Article  CAS  PubMed  Google Scholar 

  2. Loo, S. & Rine, J. Silencing and heritable domains of gene expression. Annu. Rev. Cell. Biol. Dev 11, 519–548 (1995).

    Article  CAS  Google Scholar 

  3. Hebbes, T.R., Thome, A.W. & Crane-Robinson, C. A direct link between core histone acetylation and transcriptionally active chromatin. EMBO. J. 7, 1395–1402 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lee, D., Hayes, J., Pruss, D. & Wolffe, A. A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell 72, 73–84 (1993).

    Article  CAS  PubMed  Google Scholar 

  5. Pillus, L. & Grunstein, M., Structure and Epigenetic Regulation in Yeast. in Chromatin Structure and Gene Expression (ed. Elgin, S.C.R.) (IRL Press, Oxford University Press, 1995).

    Google Scholar 

  6. Braunstein, M., Rose, A.B., Holmes, S.G., Allis, C.D. & Broach, J.R. Transcriptional silencing in yeast is associated with reduced nucleosome acetylation. Genes. Dev. 7, 592–604 (1993).

    Article  CAS  PubMed  Google Scholar 

  7. Whiteway, M., Freedman, R., Arsdell, S.V., Szostak, J.W. & Thomer, J. The yeast ARD1 gene product is required for repression of cryptic mating-type information at the HML locus. Mol. Cell. Biol. 7, 3713–22 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mullen, J.R. et al. Identification and characterization of genes and mutants for an N-terminal acetyltransferase from yeast. EMBO. J. 8, 2067–2075 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lee, F.-J.S., Lin, L.-W. & Smith, J.A. Nα-acetylation is required for normal growth and mating of Saccharomyces cerevisiae . J. Bacteriol. 171, 5795–5802 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Aparicio, O.M., Billington, B.L. & Gottschling, D.E. Modifiers of position effect are shared between telomeric and silent mating-type loci in S. cerevisiae . Cell 66, 1279–1287 (1991).

    Article  CAS  PubMed  Google Scholar 

  11. Pillus, L. & Rine, J. Epigenetic inheritance of transcriptional states in S. cerevisiae. Cell 59, 637–647 (1989).

    Article  CAS  PubMed  Google Scholar 

  12. Rivier, D. & Rine, J. Silencing: the establishment and inheritance of stable, repressed transcription states. Curr. Opin. Genet. Dev. 2, 286–292 (1992).

    Article  CAS  PubMed  Google Scholar 

  13. Miller, A.M. & Nasmyth, K.A. Role of DNA replication in the repression of silent mating type loci in yeast. Nature 312, 247–251 (1984).

    Article  CAS  PubMed  Google Scholar 

  14. Rine, J. & Herskowitz, I. Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae . Genetics 116, 9–22 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Renauld, H., Aparicio, O.M., Zierath, P.D., Billington, B.L., Chhablani, S.K. & Gottschling, D.E. Silent domains are assembled continuously from the telomere and are defined by promoter distance and strength, and by SIR3 dosage. Genes. Dev. 7, 1133–1145 (1993).

    Article  CAS  PubMed  Google Scholar 

  16. Chien, C.-T., Buck, S., Sternglanz, R. & Shore, D. Targeting of SIR1 protein establishes transcriptional silencing at HM loci and telomeres in yeast. Cell 75, 531–541 (1993).

    Article  CAS  PubMed  Google Scholar 

  17. Gottschling, D.E., Aparicio, O.M., Billington, B.L. & Zakian, V.A. Position effect at S. cerevisiae telomeres: Reversible repression of Pol II transcription. Cell 63, 751–762 (1990).

    Article  CAS  PubMed  Google Scholar 

  18. Mahoney, D., Marquardt, R., Shei, G., Rose, A. & Broach, J. Mutations in the HML E silencer of Saccharomyces cerevisiae yield metastable inheritance of trancriptional repression. Genes. Dev. 5, 605–615 (1991).

    Article  CAS  PubMed  Google Scholar 

  19. 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. 13, 3919–3928 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Karpen, G.H. Position-effect variegation and the new biology of heterochromatin. Curr. Opin. Genet. Dev. 4, 281–291 (1994).

    Article  CAS  PubMed  Google Scholar 

  21. Lyon, M.F. Controlling the Xchromosome. Curr. Biol. 3, 242–244 (1993).

    Article  CAS  PubMed  Google Scholar 

  22. Kamine, J., Elangovan, B., Subramanian, T., Coleman, D. & Chinnadurai, G. Identification of a cellular protein that specifically interacts with the essential cysteine region of the HIV-1 Tat transactivator. virology 216, 357–366 (1996).

    Article  CAS  PubMed  Google Scholar 

  23. Borrow, J. et al. The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Nature. Genet. 14, 33–41 (1996).

    Article  CAS  PubMed  Google Scholar 

  24. Spencer, F., Gerring, S.L., Connelly, C. & Hieter, P. Mitotic chromosome transmission fidelity mutants in Saccharomyces cerevisiae . Genetics 124, 237–249 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Olson, M.V. et al. Random-clone strategy for genomic restriction mapping in yeast. Proc. Natl. Acad. Sci. USA 83, 7826–7830 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Link, A.J. & Olson, M.V. Physical map of the Saccharomyces cerevisiae genome at 110-kb resolution. Genetics 127, 681–698 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Riles, L. et al. Physical maps of the six smallest chromosomes of Saccharomyces cerevisiae at a resolution of 2.6 kilobase pairs. Genetics 134, 81–150 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Altschul, S.F., Gish, W., Miller, W., Myers, E.W. & Lipman, D.J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990).

    Article  CAS  PubMed  Google Scholar 

  29. Boguski, M.S., Lowe, T.M.J. & Tolstoshev, C.M. dbEST-database for “expressed sequence tags.” Nature Genet. 4, 332–333 (1993).

    Article  CAS  PubMed  Google Scholar 

  30. Bassett, D.E., Boguski, M.S., Spencer, F., Reeves, R., Goebl, M. & Hieter, P. Comparative genomics, genome cross-referencing and XREFdb. Trends Genet. 11, 372–373 (1995).

    Article  CAS  PubMed  Google Scholar 

  31. Scherens, B., El Bakkoury, M., Vierendeels, F., Dubois, E. & Messenguy, F. Sequencing and functional analysis of a 32,650 bp segment on the left arm of yeast chromosome II. Identification of 26 open reading frames, including the KIP1 and SEC17 genes. Yeast 9, 1355–1371 (1993).

    Article  CAS  PubMed  Google Scholar 

  32. Hanslip, J.I., Swansbury, G.J., Pinkerton, R. & Catovsky, D. The translocation t(8;16)(p11;p13) defines an AML subtype with distinct cytology and clinical features. Leuk. Lymph. 6, 479–486 (1992).

    Article  Google Scholar 

  33. Tercero, J.C., Riles, L.B. & Wickner, R.B. Localized mutagenesis and evidence for post-transcriptional regulation of MAK3 . J. Biol. Chem. 267, 20270–20276 (1992).

    CAS  PubMed  Google Scholar 

  34. Kleff, S., Andrulis, E.D., Anderson, C.W. & Sternglanz, R. Identification of a gene encoding a yeast histone H4 acetyltransferase. J. Biol. Chem. 270, 24674–25677 (1995).

    Article  CAS  PubMed  Google Scholar 

  35. Brownell, J.E. et al. Tetrahymena histone acetyltransferase A: a transcriptional co-activator linking gene expression to histone acetylation. Cell 84, 843–851 (1996).

    Article  CAS  PubMed  Google Scholar 

  36. Rothstein, R. Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast. Meth. Enzym. 194, 281–301 (1991).

    Article  CAS  PubMed  Google Scholar 

  37. Boeke, J.D., Trueheart, J., Natsoulis, G. & Fink, G.R. 5-Fluoroorotic acid as a selective agent in yeast molecular genetics. Meth. Enzym. 154, 164–175 (1987).

    Article  CAS  PubMed  Google Scholar 

  38. Dillin, A. & Rine, J. On the origin of a silencer. Trends. Biochem. Sci. 20, 231–235 (1995).

    Article  CAS  PubMed  Google Scholar 

  39. Brand, A.H., Micklem, G. & Nasmyth, K. A yeast silencer contains sequences that can promote autonomous plasmid replication and transcriptional activation. Cell 51, 709–19 (1987).

    Article  CAS  PubMed  Google Scholar 

  40. Kimmerly, W., Buchman, A., Kornberg, R. & Rine, J. Roles of two DNA-binding factors in replication, segregation and transcriptional repression mediated by a yeast silencer. EMBO. J. 7, 2241–2253 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 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. 11, 1080–1091 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Shore, D. RAP1: a protean regulator in yeast. Trends. Genet. 10, 408–412 (1994).

    Article  CAS  PubMed  Google Scholar 

  43. Kennedy, B.K., Austriaco, N.R., Zhang, J. & Guarente, L. Mutation in the silencing gene SIR4 can delay aging in S. cerevisiae . Cell 80, 485–496 (1995).

    Article  CAS  PubMed  Google Scholar 

  44. Sherman, F., Moerschell, R.P., Tsunasawa, S., Sternglanz, R. & Dumont, M.E., Co-and post-translational processes and mitochondrial import of yeast cytochrome c. Translational. Regulation. of. Gene. Expression Vol. II (ed. llan, J.) (Plenum Press, 1993).

  45. Brownell, J.E. & Allis, C.D., HATs for special occasions: linking histone acetylation to chromatin assembly and gene activation. Curr. Opin. Genet. Dev. 6, 176–184 (1996).

    Article  CAS  PubMed  Google Scholar 

  46. Taunton, J., Hassig, C.A. & Schreiber, S.L. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3. Science 272, 408–411 (1996).

    Article  CAS  PubMed  Google Scholar 

  47. Berg, J.M. & Shi, Y. The galvanization of biology: a growing appreciation for the roles of zinc. Science 271, 1081–1085 (1996).

    Article  CAS  PubMed  Google Scholar 

  48. Baldarelli, R. et al. Transcripts of the Drosophila blastoderm-specific locus, terminus, are concentrated posteriorly and encode a potential DNA-binding finger. Dev. Biol. 125, 85–95 (1988).

    Article  CAS  PubMed  Google Scholar 

  49. Ruiz-i-Abata, A., Perry-O'Keefe, H. & Melton, D. Xfin: an embryonic gene encoding a mutifingered protein in Xenopus . EMBO. J. 6, 3065–3070 (1987).

    Article  Google Scholar 

  50. Morishita, K., Parker, D., Mucenski, M., Jenkins, N., Copeland, N. & Ihle, J. Retroviral activation of a novel gene encoding a zinc finger protein in IL-3-dependent myeloid leukemia lines. Cell 54, 831–840 (1988).

    Article  CAS  PubMed  Google Scholar 

  51. Tercero, J.C. & Wickner, R.B. MAK3 encodes an N-acetyltransferase whose modification of the L-A gag NH2 terminus is necessary for virus particle assembly. J. Biol. Chem. 267, 20277–20281 (1992).

    CAS  PubMed  Google Scholar 

  52. Shaw, W.V. & Leslie, A.G.W. Chloramphenical acetyltransferase. Annu. Rev. Biophys. Chem. 20, 363–386 (1991).

    Article  CAS  Google Scholar 

  53. Candau, R. et al. Identification of human proteins functionally conserved with the yeast putative adaptors ADA2 and GCN5. Mol. Cell. Biol. 16, 593–602 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Georgakopoulos, T. & Thieros, G. Two distinct yeast transcriptional activators require the function of the GCN5 protein to promote normal levels of transcription. EMBO. J. 11, 4145–4152 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Marcus, G., Silverman, N., Berger, S., Horiuchi, J. & Guarente, L. Functional similarity and physical association between GCN5 and ADA2: putative transcriptional adaptors. EMBO. J. 13, 4807–4815 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Chrivia, J.C., Kwok, R.P.S., Lamb, N., Hagiwara, M., Montminy, M.R. & Goodman, R.H. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365, 855–859 (1993).

    Article  CAS  PubMed  Google Scholar 

  57. Brownell, J.E. & Allis, C.D. An activity gel assay detects a single, catalytically active histone acetyltransferase subunit in Tetrahymena macronuclei. Proc. Natl. Acad. Sci. USA 92, 6364–6368 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Brachmann, C.B., Sherman, J.M., Devine, S.E., Cameron, E.E., Pillus, L. & Boeke, J.D. SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression and chromosome stability. Genes. Dev. 9, 2888–2902 (1995).

    Article  CAS  PubMed  Google Scholar 

  59. Savitsky, K. et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268, 1749–1753 (1995).

    Article  CAS  PubMed  Google Scholar 

  60. Greenwell, P.W., Kronmal, S., Porter, S.E., Gasenhuber, J., Obermaier, B. & Petes, T.D. TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human Ataxia telangiectasia gene. Cell 82, 823–829 (1995).

    Article  CAS  PubMed  Google Scholar 

  61. Morrow, D.W., Tagle, D.A., Shiloh, Y., Collins, F.S. & Hieter, P. TEL1, an S. cerevisiae homolog of the human gene mutated in Ataxia telaniectasia, is functionally related to the yeast checkpoint gene MEC1. Cell 82, 831–840 (1995).

    Article  CAS  PubMed  Google Scholar 

  62. Bassett, D.E., Boguski, M.S. & Hieter, P. Yeast genes and human disease. Nature 379, 589–590 (1996).

    Article  CAS  PubMed  Google Scholar 

  63. Rose, M.D., Meluh, P.B. & Hieter, P. Methods. in. Yeast. Genetics. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1990).

    Google Scholar 

  64. Sprague, G.F. Assay of yeast mating reaction. Meth. Enzym. 194, 77–93 (1991).

    Article  CAS  PubMed  Google Scholar 

  65. Lawrence, C.W. Classical mutagenesis techniques. Meth. Enzym. 194, 273–281 (1991).

    Article  CAS  PubMed  Google Scholar 

  66. Orr, W.T., Nicolas, A. & Szostak, J.W. Gene conversion adjacent to regions of double-strand break repair. Mol. Cell. Biol. 8, 5292–5298 (1988).

    Article  Google Scholar 

  67. Kulkami, M.S. & Sherman, F. NAT2, an essential gene encoding methionine Nα-acetyltransferase in the yeast Saccharomyces. cerevisiae . J. Biol. Chem. 269, 13141–13147 (1994).

    Google Scholar 

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  1. Department of Molecular, Cellular and Developmental Biology, Campus Box 347, Boulder, Colorado, 80309, USA

    Cheryl Reifsnyder, Astrid Clarke & Lorraine Pillus

  2. Departmentof Chemistry and Biochemistry, University of Colorado, Boulder, Colorado, 80309, USA

    Joanna Lowell

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Reifsnyder, C., Lowell, J., Clarke, A. et al. Yeast SAS silencing genes and human genes associated with AML and HIV–1 Tat interactions are homologous with acetyltransferases. Nat Genet 14, 42–49 (1996). https://doi.org/10.1038/ng0996-42

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