Skip to main content
PMC home page
Genetics logoLink to Genetics
. 1995 May;140(1):103–114. doi: 10.1093/genetics/140.1.103

Regulation of His4 Expression by the Saccharomyces Cerevisiae Sin4 Transcriptional Regulator

Y W Jiang 1, D J Stillman 1
PMCID: PMC1206540  PMID: 7635278

Abstract

The yeast SIN4 gene functions in the transcriptional activation and repression of diverse yeast genes. Previous experiments suggest a sin4 mutation affects chromatin structure and thus alters transcriptional regulation. In this report we show that SIN4 is required for full expression of the HIS4, Ty1, and MATα genes, in addition to the previously described SIN4-dependence of CTS1 expression. All of these genes contain within their promoters a binding site for the Rap1p transcriptional regulator. However, SIN4 does not play a direct role either in transcriptional activation or repression by Rap1p. The HIS4 gene can be activated by either of two pathways, the basal or the inducible pathway, and experiments are described that show that a sin4 mutation affects both pathways. It was shown previously that mutation of the Rap1p binding site in the HIS4 promoter causes a similar effect on HIS4 expression and that this promoter mutation also causes a change in chromatin structure. The SNF2/SWI2 gene is also required for full HIS4 expression, and we show that a sin4 snf2 double mutant is not synergistic compared to either single mutant. We show that nucleosomes are positioned at the HIS4 promoter and that this positioning is disrupted in a snf2 mutant but not in a sin4 mutant. These findings suggest that SIN4 plays a distinct role in transcriptional regulation.

Full Text

The Full Text of this article is available as a PDF (5.5 MB).

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. Arndt K. T., Styles C., Fink G. R. Multiple global regulators control HIS4 transcription in yeast. Science. 1987 Aug 21;237(4817):874–880. doi: 10.1126/science.3303332. [DOI] [PubMed] [Google Scholar]
  3. Brand A. H., 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. doi: 10.1016/0092-8674(87)90094-8. [DOI] [PubMed] [Google Scholar]
  4. Brazas R. M., Stillman D. J. The Swi5 zinc-finger and Grf10 homeodomain proteins bind DNA cooperatively at the yeast HO promoter. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11237–11241. doi: 10.1073/pnas.90.23.11237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Breeden L., Nasmyth K. Cell cycle control of the yeast HO gene: cis- and trans-acting regulators. Cell. 1987 Feb 13;48(3):389–397. doi: 10.1016/0092-8674(87)90190-5. [DOI] [PubMed] [Google Scholar]
  6. Cairns B. R., Kim Y. J., Sayre M. H., Laurent B. C., Kornberg R. D. A multisubunit complex containing the SWI1/ADR6, SWI2/SNF2, SWI3, SNF5, and SNF6 gene products isolated from yeast. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1950–1954. doi: 10.1073/pnas.91.5.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen S., West R. W., Jr, Ma J., Johnson S. L., Gans H., Woldehawariat G. TSF1 to TSF6, required for silencing the Saccharomyces cerevisiae GAL genes, are global regulatory genes. Genetics. 1993 Jul;134(3):701–716. doi: 10.1093/genetics/134.3.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ciriacy M., Freidel K., Löhning C. Characterization of trans-acting mutations affecting Ty and Ty-mediated transcription in Saccharomyces cerevisiae. Curr Genet. 1991 Dec;20(6):441–448. doi: 10.1007/BF00334769. [DOI] [PubMed] [Google Scholar]
  9. Covitz P. A., Song W., Mitchell A. P. Requirement for RGR1 and SIN4 in RME1-dependent repression in Saccharomyces cerevisiae. Genetics. 1994 Nov;138(3):577–586. doi: 10.1093/genetics/138.3.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Côté J., Quinn J., Workman J. L., Peterson C. L. Stimulation of GAL4 derivative binding to nucleosomal DNA by the yeast SWI/SNF complex. Science. 1994 Jul 1;265(5168):53–60. doi: 10.1126/science.8016655. [DOI] [PubMed] [Google Scholar]
  11. Daignan-Fornier B., Fink G. R. Coregulation of purine and histidine biosynthesis by the transcriptional activators BAS1 and BAS2. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6746–6750. doi: 10.1073/pnas.89.15.6746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Devlin C., Tice-Baldwin K., Shore D., Arndt K. T. RAP1 is required for BAS1/BAS2- and GCN4-dependent transcription of the yeast HIS4 gene. Mol Cell Biol. 1991 Jul;11(7):3642–3651. doi: 10.1128/mcb.11.7.3642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dohrmann P. R., Butler G., Tamai K., Dorland S., Greene J. R., Thiele D. J., Stillman D. J. Parallel pathways of gene regulation: homologous regulators SWI5 and ACE2 differentially control transcription of HO and chitinase. Genes Dev. 1992 Jan;6(1):93–104. doi: 10.1101/gad.6.1.93. [DOI] [PubMed] [Google Scholar]
  14. Doorenbosch T., Mager W. H., Planta R. J. Multifunctional DNA-binding proteins in yeast. Gene Expr. 1992;2(3):193–201. [PMC free article] [PubMed] [Google Scholar]
  15. Drysdale C. M., Dueñas E., Jackson B. M., Reusser U., Braus G. H., Hinnebusch A. G. The transcriptional activator GCN4 contains multiple activation domains that are critically dependent on hydrophobic amino acids. Mol Cell Biol. 1995 Mar;15(3):1220–1233. doi: 10.1128/mcb.15.3.1220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Durrin L. K., Mann R. K., Grunstein M. Nucleosome loss activates CUP1 and HIS3 promoters to fully induced levels in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1992 Apr;12(4):1621–1629. doi: 10.1128/mcb.12.4.1621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fascher K. D., Schmitz J., Hörz W. Role of trans-activating proteins in the generation of active chromatin at the PHO5 promoter in S. cerevisiae. EMBO J. 1990 Aug;9(8):2523–2528. doi: 10.1002/j.1460-2075.1990.tb07432.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fassler J. S., Gray W., Lee J. P., Yu G. Y., Gingerich G. The Saccharomyces cerevisiae SPT14 gene is essential for normal expression of the yeast transposon, Ty, as well as for expression of the HIS4 gene and several genes in the mating pathway. Mol Gen Genet. 1991 Nov;230(1-2):310–320. doi: 10.1007/BF00290682. [DOI] [PubMed] [Google Scholar]
  19. Giesman D., Best L., Tatchell K. The role of RAP1 in the regulation of the MAT alpha locus. Mol Cell Biol. 1991 Feb;11(2):1069–1079. doi: 10.1128/mcb.11.2.1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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. 1990 Nov 16;63(4):751–762. doi: 10.1016/0092-8674(90)90141-z. [DOI] [PubMed] [Google Scholar]
  21. Gray W. M., Fassler J. S. Role of Saccharomyces cerevisiae Rap1 protein in Ty1 and Ty1-mediated transcription. Gene Expr. 1993;3(3):237–251. [PMC free article] [PubMed] [Google Scholar]
  22. Guarente L., Lalonde B., Gifford P., Alani E. Distinctly regulated tandem upstream activation sites mediate catabolite repression of the CYC1 gene of S. cerevisiae. Cell. 1984 Feb;36(2):503–511. doi: 10.1016/0092-8674(84)90243-5. [DOI] [PubMed] [Google Scholar]
  23. Happel A. M., Swanson M. S., Winston F. The SNF2, SNF5 and SNF6 genes are required for Ty transcription in Saccharomyces cerevisiae. Genetics. 1991 May;128(1):69–77. doi: 10.1093/genetics/128.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hirschhorn J. N., Brown S. A., Clark C. D., Winston F. Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure. Genes Dev. 1992 Dec;6(12A):2288–2298. doi: 10.1101/gad.6.12a.2288. [DOI] [PubMed] [Google Scholar]
  25. Hofmann J. F., Laroche T., Brand A. H., Gasser S. M. RAP-1 factor is necessary for DNA loop formation in vitro at the silent mating type locus HML. Cell. 1989 Jun 2;57(5):725–737. doi: 10.1016/0092-8674(89)90788-5. [DOI] [PubMed] [Google Scholar]
  26. Imbalzano A. N., Kwon H., Green M. R., Kingston R. E. Facilitated binding of TATA-binding protein to nucleosomal DNA. Nature. 1994 Aug 11;370(6489):481–485. doi: 10.1038/370481a0. [DOI] [PubMed] [Google Scholar]
  27. Ito H., Fukuda Y., Murata K., Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. doi: 10.1128/jb.153.1.163-168.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Jiang Y. W., Stillman D. J. Involvement of the SIN4 global transcriptional regulator in the chromatin structure of Saccharomyces cerevisiae. Mol Cell Biol. 1992 Oct;12(10):4503–4514. doi: 10.1128/mcb.12.10.4503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Kurtz S., Shore D. RAP1 protein activates and silences transcription of mating-type genes in yeast. Genes Dev. 1991 Apr;5(4):616–628. doi: 10.1101/gad.5.4.616. [DOI] [PubMed] [Google Scholar]
  31. Kwon H., Imbalzano A. N., Khavari P. A., Kingston R. E., Green M. R. Nucleosome disruption and enhancement of activator binding by a human SW1/SNF complex. Nature. 1994 Aug 11;370(6489):477–481. doi: 10.1038/370477a0. [DOI] [PubMed] [Google Scholar]
  32. Kyrion G., Liu K., Liu C., Lustig A. J. RAP1 and telomere structure regulate telomere position effects in Saccharomyces cerevisiae. Genes Dev. 1993 Jul;7(7A):1146–1159. doi: 10.1101/gad.7.7a.1146. [DOI] [PubMed] [Google Scholar]
  33. Laurent B. C., Carlson M. Yeast SNF2/SWI2, SNF5, and SNF6 proteins function coordinately with the gene-specific transcriptional activators GAL4 and Bicoid. Genes Dev. 1992 Sep;6(9):1707–1715. doi: 10.1101/gad.6.9.1707. [DOI] [PubMed] [Google Scholar]
  34. Laurent B. C., Treitel M. A., Carlson M. Functional interdependence of the yeast SNF2, SNF5, and SNF6 proteins in transcriptional activation. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2687–2691. doi: 10.1073/pnas.88.7.2687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Lustig A. J., Kurtz S., Shore D. Involvement of the silencer and UAS binding protein RAP1 in regulation of telomere length. Science. 1990 Oct 26;250(4980):549–553. doi: 10.1126/science.2237406. [DOI] [PubMed] [Google Scholar]
  36. Matallana E., Franco L., Pérez-Ortín J. E. Chromatin structure of the yeast SUC2 promoter in regulatory mutants. Mol Gen Genet. 1992 Feb;231(3):395–400. doi: 10.1007/BF00292708. [DOI] [PubMed] [Google Scholar]
  37. Mueller P. P., Hinnebusch A. G. Multiple upstream AUG codons mediate translational control of GCN4. Cell. 1986 Apr 25;45(2):201–207. doi: 10.1016/0092-8674(86)90384-3. [DOI] [PubMed] [Google Scholar]
  38. Nasmyth K., Stillman D., Kipling D. Both positive and negative regulators of HO transcription are required for mother-cell-specific mating-type switching in yeast. Cell. 1987 Feb 27;48(4):579–587. doi: 10.1016/0092-8674(87)90236-4. [DOI] [PubMed] [Google Scholar]
  39. Nasmyth K. The determination of mother cell-specific mating type switching in yeast by a specific regulator of HO transcription. EMBO J. 1987 Jan;6(1):243–248. doi: 10.1002/j.1460-2075.1987.tb04745.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Peterson C. L., Herskowitz I. Characterization of the yeast SWI1, SWI2, and SWI3 genes, which encode a global activator of transcription. Cell. 1992 Feb 7;68(3):573–583. doi: 10.1016/0092-8674(92)90192-f. [DOI] [PubMed] [Google Scholar]
  41. Rose M. D., Novick P., Thomas J. H., Botstein D., Fink G. R. A Saccharomyces cerevisiae genomic plasmid bank based on a centromere-containing shuttle vector. Gene. 1987;60(2-3):237–243. doi: 10.1016/0378-1119(87)90232-0. [DOI] [PubMed] [Google Scholar]
  42. Rothstein R. Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast. Methods Enzymol. 1991;194:281–301. doi: 10.1016/0076-6879(91)94022-5. [DOI] [PubMed] [Google Scholar]
  43. Runge K. W., Zakian V. A. Properties of the transcriptional enhancer in Saccharomyces cerevisiae telomeres. Nucleic Acids Res. 1990 Apr 11;18(7):1783–1787. doi: 10.1093/nar/18.7.1783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sikorski R. S., Boeke J. D. In vitro mutagenesis and plasmid shuffling: from cloned gene to mutant yeast. Methods Enzymol. 1991;194:302–318. doi: 10.1016/0076-6879(91)94023-6. [DOI] [PubMed] [Google Scholar]
  45. Sikorski R. S., 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. doi: 10.1093/genetics/122.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sprague G. F., Jr Assay of yeast mating reaction. Methods Enzymol. 1991;194:77–93. doi: 10.1016/0076-6879(91)94008-z. [DOI] [PubMed] [Google Scholar]
  47. Sternberg P. W., Stern M. J., Clark I., Herskowitz I. Activation of the yeast HO gene by release from multiple negative controls. Cell. 1987 Feb 27;48(4):567–577. doi: 10.1016/0092-8674(87)90235-2. [DOI] [PubMed] [Google Scholar]
  48. Stillman D. J., Dorland S., Yu Y. Epistasis analysis of suppressor mutations that allow HO expression in the absence of the yeast SW15 transcriptional activator. Genetics. 1994 Mar;136(3):781–788. doi: 10.1093/genetics/136.3.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Thomas B. J., Rothstein R. Elevated recombination rates in transcriptionally active DNA. Cell. 1989 Feb 24;56(4):619–630. doi: 10.1016/0092-8674(89)90584-9. [DOI] [PubMed] [Google Scholar]
  50. Winston F., Carlson M. Yeast SNF/SWI transcriptional activators and the SPT/SIN chromatin connection. Trends Genet. 1992 Nov;8(11):387–391. doi: 10.1016/0168-9525(92)90300-s. [DOI] [PubMed] [Google Scholar]
  51. Yoshida K., Ogawa N., Oshima Y. Function of the PHO regulatory genes for repressible acid phosphatase synthesis in Saccharomyces cerevisiae. Mol Gen Genet. 1989 May;217(1):40–46. doi: 10.1007/BF00330940. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES