Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 2000 Nov;156(3):933–941. doi: 10.1093/genetics/156.3.933

MGA2 and SPT23 are modifiers of transcriptional silencing in yeast.

M L Dula 1, S G Holmes 1
PMCID: PMC1461329  PMID: 11063674

Abstract

Transcriptional silencing at the HM loci and telomeres in yeast depends on several trans-acting factors, including Rap1p and the Sir proteins. The SUM1-1 mutation was identified by its ability to restore silencing to strains deficient in one or more of these trans-acting factors. The mechanism by which SUM1-1 bypasses the requirement for silencing proteins is not known. We identified four loci that when reduced in dosage in diploid strains increase the ability of SUM1-1 strains to suppress silencing defects. Two of the genes responsible for this effect were found to be MGA2 and SPT23. Mga2p and Spt23p were previously identified as functionally related transcription factors that influence chromatin structure. We find that deletion of MGA2 or SPT23 also increases the efficiency of silencing in haploid SUM1-1 strains. These results suggest that Mga2p and Spt23p are antagonists of silencing. Consistent with this proposal we find that deletion of MGA2 or SPT23 also suppresses the silencing defects caused by deletion of the SIR1 gene or by mutations in the HMR silencer sequences. However, we find that Mga2p and Spt23p can positively affect silencing in other contexts; deletion of either MGA2 or SPT23 decreases mating in strains bearing mutations in the HML-E silencer. Mga2p and Spt23p appear to be a novel class of factors that influence disparate pathways of transcriptional control by chromatin.

Full Text

The Full Text of this article is available as a PDF (375.6 KB).

Selected References

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

  1. 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. 1991 Sep 20;66(6):1279–1287. doi: 10.1016/0092-8674(91)90049-5. [DOI] [PubMed] [Google Scholar]
  2. 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. 1993 Apr;7(4):592–604. doi: 10.1101/gad.7.4.592. [DOI] [PubMed] [Google Scholar]
  3. Burkett T. J., Garfinkel D. J. Molecular characterization of the SPT23 gene: a dosage-dependent suppressor of Ty-induced promoter mutations from Saccharomyces cerevisiae. Yeast. 1994 Jan;10(1):81–92. doi: 10.1002/yea.320100108. [DOI] [PubMed] [Google Scholar]
  4. Churcher C., Bowman S., Badcock K., Bankier A., Brown D., Chillingworth T., Connor R., Devlin K., Gentles S., Hamlin N. The nucleotide sequence of Saccharomyces cerevisiae chromosome IX. Nature. 1997 May 29;387(6632 Suppl):84–87. [PubMed] [Google Scholar]
  5. Clark-Adams C. D., Norris D., Osley M. A., Fassler J. S., Winston F. Changes in histone gene dosage alter transcription in yeast. Genes Dev. 1988 Feb;2(2):150–159. doi: 10.1101/gad.2.2.150. [DOI] [PubMed] [Google Scholar]
  6. Cockell M., Palladino F., Laroche T., Kyrion G., Liu C., Lustig A. J., Gasser S. M. The carboxy termini of Sir4 and Rap1 affect Sir3 localization: evidence for a multicomponent complex required for yeast telomeric silencing. J Cell Biol. 1995 May;129(4):909–924. doi: 10.1083/jcb.129.4.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Holmes S. G., Rose A. B., Steuerle K., Saez E., Sayegh S., Lee Y. M., Broach J. R. Hyperactivation of the silencing proteins, Sir2p and Sir3p, causes chromosome loss. Genetics. 1997 Mar;145(3):605–614. doi: 10.1093/genetics/145.3.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Klar A. J., Kakar S. N., Ivy J. M., Hicks J. B., Livi G. P., Miglio L. M. SUM1, an apparent positive regulator of the cryptic mating-type loci in Saccharomyces cerevisiae. Genetics. 1985 Dec;111(4):745–758. doi: 10.1093/genetics/111.4.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kornberg R. D., Lorch Y. Chromatin-modifying and -remodeling complexes. Curr Opin Genet Dev. 1999 Apr;9(2):148–151. doi: 10.1016/S0959-437X(99)80022-7. [DOI] [PubMed] [Google Scholar]
  12. Landry J., Sutton A., Tafrov S. T., Heller R. C., Stebbins J., Pillus L., Sternglanz R. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc Natl Acad Sci U S A. 2000 May 23;97(11):5807–5811. doi: 10.1073/pnas.110148297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Laurenson P., Rine J. SUM1-1: a suppressor of silencing defects in Saccharomyces cerevisiae. Genetics. 1991 Nov;129(3):685–696. doi: 10.1093/genetics/129.3.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Locke J., Kotarski M. A., Tartof K. D. Dosage-dependent modifiers of position effect variegation in Drosophila and a mass action model that explains their effect. Genetics. 1988 Sep;120(1):181–198. doi: 10.1093/genetics/120.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Moazed D., Kistler A., Axelrod A., Rine J., Johnson A. D. Silent information regulator protein complexes in Saccharomyces cerevisiae: a SIR2/SIR4 complex and evidence for a regulatory domain in SIR4 that inhibits its interaction with SIR3. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2186–2191. doi: 10.1073/pnas.94.6.2186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Pillus L., Rine J. Epigenetic inheritance of transcriptional states in S. cerevisiae. Cell. 1989 Nov 17;59(4):637–647. doi: 10.1016/0092-8674(89)90009-3. [DOI] [PubMed] [Google Scholar]
  18. Ross-Macdonald P., Sheehan A., Friddle C., Roeder G. S., Snyder M. Transposon mutagenesis for the analysis of protein production, function, and localization. Methods Enzymol. 1999;303:512–532. doi: 10.1016/s0076-6879(99)03031-1. [DOI] [PubMed] [Google Scholar]
  19. Shei G. J., Broach J. R. Yeast silencers can act as orientation-dependent gene inactivation centers that respond to environmental signals. Mol Cell Biol. 1995 Jul;15(7):3496–3506. doi: 10.1128/mcb.15.7.3496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Stone E. M., Swanson M. J., Romeo A. M., Hicks J. B., Sternglanz R. The SIR1 gene of Saccharomyces cerevisiae and its role as an extragenic suppressor of several mating-defective mutants. Mol Cell Biol. 1991 Apr;11(4):2253–2262. doi: 10.1128/mcb.11.4.2253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. 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. doi: 10.1128/mcb.13.7.3919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tanny J. C., Dowd G. J., Huang J., Hilz H., Moazed D. An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing. Cell. 1999 Dec 23;99(7):735–745. doi: 10.1016/s0092-8674(00)81671-2. [DOI] [PubMed] [Google Scholar]
  24. Travers A. An engine for nucleosome remodeling. Cell. 1999 Feb 5;96(3):311–314. doi: 10.1016/s0092-8674(00)80543-7. [DOI] [PubMed] [Google Scholar]
  25. 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. doi: 10.1038/381251a0. [DOI] [PubMed] [Google Scholar]
  26. Winzeler E. A., Shoemaker D. D., Astromoff A., Liang H., Anderson K., Andre B., Bangham R., Benito R., Boeke J. D., Bussey H. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science. 1999 Aug 6;285(5429):901–906. doi: 10.1126/science.285.5429.901. [DOI] [PubMed] [Google Scholar]
  27. Xie J., Pierce M., Gailus-Durner V., Wagner M., Winter E., Vershon A. K. Sum1 and Hst1 repress middle sporulation-specific gene expression during mitosis in Saccharomyces cerevisiae. EMBO J. 1999 Nov 15;18(22):6448–6454. doi: 10.1093/emboj/18.22.6448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Zhang S., Burkett T. J., Yamashita I., Garfinkel D. J. Genetic redundancy between SPT23 and MGA2: regulators of Ty-induced mutations and Ty1 transcription in Saccharomyces cerevisiae. Mol Cell Biol. 1997 Aug;17(8):4718–4729. doi: 10.1128/mcb.17.8.4718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zhang S., Skalsky Y., Garfinkel D. J. MGA2 or SPT23 is required for transcription of the delta9 fatty acid desaturase gene, OLE1, and nuclear membrane integrity in Saccharomyces cerevisiae. Genetics. 1999 Feb;151(2):473–483. doi: 10.1093/genetics/151.2.473. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES