Skip to main content
PMC home page
Genetics logoLink to Genetics
. 1999 Sep;153(1):13–23. doi: 10.1093/genetics/153.1.13

Identification of SAS4 and SAS5, two genes that regulate silencing in Saccharomyces cerevisiae.

E Y Xu 1, S Kim 1, K Replogle 1, J Rine 1, D H Rivier 1
PMCID: PMC1460750  PMID: 10471696

Abstract

In Saccharomyces cerevisiae, chromatin-mediated silencing inactivates transcription of the genes at the HML and HMR cryptic mating-type loci and genes near telomeres. Mutations in the Rap1p and Abf1p binding sites of the HMR-E silencer (HMRa-e**) result in a loss of silencing at HMR. We characterized a collection of 15 mutations that restore the alpha-mating phenotype to MATalpha HMRa-e** strains. These mutations defined three complementation groups, two new groups and one group that corresponded to the previously identified SAS2 gene. We cloned the genes that complemented members of the new groups and identified two previously uncharacterized genes, which we named SAS4 and SAS5. Neither SAS4 nor SAS5 was required for viability. Null alleles of SAS4 and SAS5 restored SIR4-dependent silencing at HMR, establishing that each is a regulator of silencing. Null alleles of SAS4 and SAS5 bypassed the role of the Abf1p binding site of the HMR-E silencer but not the role of the ACS or Rap1p binding site. Previous analysis indicated that SAS2 is homologous to a human gene that is a site of recurring translocations involved in acute myeloid leukemia. Similarly, SAS5 is a member of a gene family that included two human genes that are the sites of recurring translocations involved in acute myeloid leukemia.

Full Text

The Full Text of this article is available as a PDF (264.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abraham J., Nasmyth K. A., Strathern J. N., Klar A. J., Hicks J. B. Regulation of mating-type information in yeast. Negative control requiring sequences both 5' and 3' to the regulated region. J Mol Biol. 1984 Jul 5;176(3):307–331. doi: 10.1016/0022-2836(84)90492-3. [DOI] [PubMed] [Google Scholar]
  2. 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. doi: 10.1128/mcb.11.2.1080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bannister A. J., Kouzarides T. The CBP co-activator is a histone acetyltransferase. Nature. 1996 Dec 19;384(6610):641–643. doi: 10.1038/384641a0. [DOI] [PubMed] [Google Scholar]
  4. Baudin A., Ozier-Kalogeropoulos O., Denouel A., Lacroute F., Cullin C. A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae. Nucleic Acids Res. 1993 Jul 11;21(14):3329–3330. doi: 10.1093/nar/21.14.3329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Borrow J., Stanton V. P., Jr, Andresen J. M., Becher R., Behm F. G., Chaganti R. S., Civin C. I., Disteche C., Dubé I., Frischauf A. M. The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Nat Genet. 1996 Sep;14(1):33–41. doi: 10.1038/ng0996-33. [DOI] [PubMed] [Google Scholar]
  6. Brand A. H., Breeden L., Abraham J., Sternglanz R., Nasmyth K. Characterization of a "silencer" in yeast: a DNA sequence with properties opposite to those of a transcriptional enhancer. Cell. 1985 May;41(1):41–48. doi: 10.1016/0092-8674(85)90059-5. [DOI] [PubMed] [Google Scholar]
  7. Braunstein M., Sobel R. E., Allis C. D., Turner B. M., Broach J. R. Efficient transcriptional silencing in Saccharomyces cerevisiae requires a heterochromatin histone acetylation pattern. Mol Cell Biol. 1996 Aug;16(8):4349–4356. doi: 10.1128/mcb.16.8.4349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brownell J. E., Allis C. D. Special HATs for special occasions: linking histone acetylation to chromatin assembly and gene activation. Curr Opin Genet Dev. 1996 Apr;6(2):176–184. doi: 10.1016/s0959-437x(96)80048-7. [DOI] [PubMed] [Google Scholar]
  9. Brownell J. E., Zhou J., Ranalli T., Kobayashi R., Edmondson D. G., Roth S. Y., Allis C. D. Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell. 1996 Mar 22;84(6):843–851. doi: 10.1016/s0092-8674(00)81063-6. [DOI] [PubMed] [Google Scholar]
  10. Cairns B. R., Henry N. L., Kornberg R. D. TFG/TAF30/ANC1, a component of the yeast SWI/SNF complex that is similar to the leukemogenic proteins ENL and AF-9. Mol Cell Biol. 1996 Jul;16(7):3308–3316. doi: 10.1128/mcb.16.7.3308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Carapeti M., Aguiar R. C., Goldman J. M., Cross N. C. A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia. Blood. 1998 May 1;91(9):3127–3133. [PubMed] [Google Scholar]
  12. Chien C. T., Buck S., Sternglanz R., Shore D. Targeting of SIR1 protein establishes transcriptional silencing at HM loci and telomeres in yeast. Cell. 1993 Nov 5;75(3):531–541. doi: 10.1016/0092-8674(93)90387-6. [DOI] [PubMed] [Google Scholar]
  13. Cleary M. L. Oncogenic conversion of transcription factors by chromosomal translocations. Cell. 1991 Aug 23;66(4):619–622. doi: 10.1016/0092-8674(91)90105-8. [DOI] [PubMed] [Google Scholar]
  14. Cleary M. L. Transcription factors in human leukaemias. Cancer Surv. 1992;15:89–104. [PubMed] [Google Scholar]
  15. Feldman J. B., Hicks J. B., Broach J. R. Identification of sites required for repression of a silent mating type locus in yeast. J Mol Biol. 1984 Oct 5;178(4):815–834. doi: 10.1016/0022-2836(84)90313-9. [DOI] [PubMed] [Google Scholar]
  16. Foss M., McNally F. J., 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. doi: 10.1126/science.8266071. [DOI] [PubMed] [Google Scholar]
  17. Fox C. A., Ehrenhofer-Murray A. E., Loo S., Rine J. The origin recognition complex, SIR1, and the S phase requirement for silencing. Science. 1997 Jun 6;276(5318):1547–1551. doi: 10.1126/science.276.5318.1547. [DOI] [PubMed] [Google Scholar]
  18. Hecht A., Laroche T., Strahl-Bolsinger S., Gasser S. M., Grunstein M. Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast. Cell. 1995 Feb 24;80(4):583–592. doi: 10.1016/0092-8674(95)90512-x. [DOI] [PubMed] [Google Scholar]
  19. Hecht A., Strahl-Bolsinger S., Grunstein M. Spreading of transcriptional repressor SIR3 from telomeric heterochromatin. Nature. 1996 Sep 5;383(6595):92–96. doi: 10.1038/383092a0. [DOI] [PubMed] [Google Scholar]
  20. Henry N. L., Campbell A. M., Feaver W. J., Poon D., Weil P. A., Kornberg R. D. TFIIF-TAF-RNA polymerase II connection. Genes Dev. 1994 Dec 1;8(23):2868–2878. doi: 10.1101/gad.8.23.2868. [DOI] [PubMed] [Google Scholar]
  21. Holstege F. C., Jennings E. G., Wyrick J. J., Lee T. I., Hengartner C. J., Green M. R., Golub T. R., Lander E. S., Young R. A. Dissecting the regulatory circuitry of a eukaryotic genome. Cell. 1998 Nov 25;95(5):717–728. doi: 10.1016/s0092-8674(00)81641-4. [DOI] [PubMed] [Google Scholar]
  22. Jones J. S., Prakash L. Yeast Saccharomyces cerevisiae selectable markers in pUC18 polylinkers. Yeast. 1990 Sep-Oct;6(5):363–366. doi: 10.1002/yea.320060502. [DOI] [PubMed] [Google Scholar]
  23. Jones R. S., Gelbart W. M. The Drosophila Polycomb-group gene Enhancer of zeste contains a region with sequence similarity to trithorax. Mol Cell Biol. 1993 Oct;13(10):6357–6366. doi: 10.1128/mcb.13.10.6357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kim Y. J., Björklund S., Li Y., Sayre M. H., Kornberg R. D. A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II. Cell. 1994 May 20;77(4):599–608. doi: 10.1016/0092-8674(94)90221-6. [DOI] [PubMed] [Google Scholar]
  25. Kuo M. H., Zhou J., Jambeck P., Churchill M. E., Allis C. D. Histone acetyltransferase activity of yeast Gcn5p is required for the activation of target genes in vivo. Genes Dev. 1998 Mar 1;12(5):627–639. doi: 10.1101/gad.12.5.627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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. doi: 10.1093/genetics/141.3.889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Loo S., Rine J. Silencers and domains of generalized repression. Science. 1994 Jun 17;264(5166):1768–1771. doi: 10.1126/science.8209257. [DOI] [PubMed] [Google Scholar]
  28. Lustig A. J. Mechanisms of silencing in Saccharomyces cerevisiae. Curr Opin Genet Dev. 1998 Apr;8(2):233–239. doi: 10.1016/s0959-437x(98)80146-9. [DOI] [PubMed] [Google Scholar]
  29. McNally F. J., Rine J. A synthetic silencer mediates SIR-dependent functions in Saccharomyces cerevisiae. Mol Cell Biol. 1991 Nov;11(11):5648–5659. doi: 10.1128/mcb.11.11.5648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mizzen C. A., Yang X. J., Kokubo T., Brownell J. E., Bannister A. J., Owen-Hughes T., Workman J., Wang L., Berger S. L., Kouzarides T. The TAF(II)250 subunit of TFIID has histone acetyltransferase activity. Cell. 1996 Dec 27;87(7):1261–1270. doi: 10.1016/s0092-8674(00)81821-8. [DOI] [PubMed] [Google Scholar]
  31. Moretti P., Freeman K., Coodly L., Shore D. Evidence that a complex of SIR proteins interacts with the silencer and telomere-binding protein RAP1. Genes Dev. 1994 Oct 1;8(19):2257–2269. doi: 10.1101/gad.8.19.2257. [DOI] [PubMed] [Google Scholar]
  32. Nakamura T., Alder H., Gu Y., Prasad R., Canaani O., Kamada N., Gale R. P., Lange B., Crist W. M., Nowell P. C. Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4631–4635. doi: 10.1073/pnas.90.10.4631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Nislow C., Ray E., Pillus L. SET1, a yeast member of the trithorax family, functions in transcriptional silencing and diverse cellular processes. Mol Biol Cell. 1997 Dec;8(12):2421–2436. doi: 10.1091/mbc.8.12.2421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rabbitts T. H. Chromosomal translocations in human cancer. Nature. 1994 Nov 10;372(6502):143–149. doi: 10.1038/372143a0. [DOI] [PubMed] [Google Scholar]
  35. Rivier D. H., Ekena J. L., Rine J. HMR-I is an origin of replication and a silencer in Saccharomyces cerevisiae. Genetics. 1999 Feb;151(2):521–529. doi: 10.1093/genetics/151.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rowley J. D., Reshmi S., Sobulo O., Musvee T., Anastasi J., Raimondi S., Schneider N. R., Barredo J. C., Cantu E. S., Schlegelberger B. All patients with the T(11;16)(q23;p13.3) that involves MLL and CBP have treatment-related hematologic disorders. Blood. 1997 Jul 15;90(2):535–541. [PubMed] [Google Scholar]
  37. Rundlett S. E., Carmen A. A., Suka N., Turner B. M., Grunstein M. Transcriptional repression by UME6 involves deacetylation of lysine 5 of histone H4 by RPD3. Nature. 1998 Apr 23;392(6678):831–835. doi: 10.1038/33952. [DOI] [PubMed] [Google Scholar]
  38. Schnitzler G., Sif S., Kingston R. E. Human SWI/SNF interconverts a nucleosome between its base state and a stable remodeled state. Cell. 1998 Jul 10;94(1):17–27. doi: 10.1016/s0092-8674(00)81217-9. [DOI] [PubMed] [Google Scholar]
  39. Shore D., Nasmyth K. Purification and cloning of a DNA binding protein from yeast that binds to both silencer and activator elements. Cell. 1987 Dec 4;51(5):721–732. doi: 10.1016/0092-8674(87)90095-x. [DOI] [PubMed] [Google Scholar]
  40. Smith E. R., Eisen A., Gu W., Sattah M., Pannuti A., Zhou J., Cook R. G., Lucchesi J. C., Allis C. D. ESA1 is a histone acetyltransferase that is essential for growth in yeast. Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3561–3565. doi: 10.1073/pnas.95.7.3561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Smith J. S., Boeke J. D. An unusual form of transcriptional silencing in yeast ribosomal DNA. Genes Dev. 1997 Jan 15;11(2):241–254. doi: 10.1101/gad.11.2.241. [DOI] [PubMed] [Google Scholar]
  42. Spencer F., Gerring S. L., Connelly C., Hieter P. Mitotic chromosome transmission fidelity mutants in Saccharomyces cerevisiae. Genetics. 1990 Feb;124(2):237–249. doi: 10.1093/genetics/124.2.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Strahl-Bolsinger S., Hecht A., Luo K., Grunstein M. SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast. Genes Dev. 1997 Jan 1;11(1):83–93. doi: 10.1101/gad.11.1.83. [DOI] [PubMed] [Google Scholar]
  44. Tenen D. G., Hromas R., Licht J. D., Zhang D. E. Transcription factors, normal myeloid development, and leukemia. Blood. 1997 Jul 15;90(2):489–519. [PubMed] [Google Scholar]
  45. Tkachuk D. C., Kohler S., Cleary M. L. Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell. 1992 Nov 13;71(4):691–700. doi: 10.1016/0092-8674(92)90602-9. [DOI] [PubMed] [Google Scholar]
  46. Varga-Weisz P. D., Becker P. B. Chromatin-remodeling factors: machines that regulate? Curr Opin Cell Biol. 1998 Jun;10(3):346–353. doi: 10.1016/s0955-0674(98)80010-0. [DOI] [PubMed] [Google Scholar]
  47. Wach A., Brachat A., Pöhlmann R., Philippsen P. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast. 1994 Dec;10(13):1793–1808. doi: 10.1002/yea.320101310. [DOI] [PubMed] [Google Scholar]
  48. Wotton D., Shore D. A novel Rap1p-interacting factor, Rif2p, cooperates with Rif1p to regulate telomere length in Saccharomyces cerevisiae. Genes Dev. 1997 Mar 15;11(6):748–760. doi: 10.1101/gad.11.6.748. [DOI] [PubMed] [Google Scholar]
  49. Xu E. Y., Kim S., Rivier D. H. SAS4 and SAS5 are locus-specific regulators of silencing in Saccharomyces cerevisiae. Genetics. 1999 Sep;153(1):25–33. doi: 10.1093/genetics/153.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Yamamoto T., Horikoshi M. Novel substrate specificity of the histone acetyltransferase activity of HIV-1-Tat interactive protein Tip60. J Biol Chem. 1997 Dec 5;272(49):30595–30598. doi: 10.1074/jbc.272.49.30595. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES