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. 1991 Dec;11(12):6306–6316. doi: 10.1128/mcb.11.12.6306

RPD1 (SIN3/UME4) is required for maximal activation and repression of diverse yeast genes.

M Vidal 1, R Strich 1, R E Esposito 1, R F Gaber 1
PMCID: PMC361824  PMID: 1944290

Abstract

We show that the extent of transcriptional regulation of many, apparently unrelated, genes in Saccharomyces cerevisiae is dependent on RPD1 (and RPD3 [M. Vidal and R. F. Gaber, Mol. Cell. Biol. 11:6317-6327, 1991]). Genes regulated by stimuli as diverse as external signals (PHO5), cell differentiation processes (SPO11 and SPO13), cell type (RME1, FUS1, HO, TY2, STE6, STE3, and BAR1), and genes whose regulatory signals remain unknown (TRK2) depend on RPD1 to achieve maximal states of transcriptional regulation. RPD1 enhances both positive and negative regulation of these genes: in rpd1 delta mutants, higher levels of expression are observed under repression conditions and lower levels are observed under activation conditions. We show that several independent genetic screens, designed to identify yeast transcriptional regulators, have detected the RPD1 locus (also known as SIN3, SD11, and UME4). The inferred RPD1 protein contains four regions predicted to take on helix-loop-helix-like secondary structures and three regions (acidic, glutamine rich, and proline rich) reminiscent of the activating domains of transcriptional activators.

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Selected References

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

  1. Ammerer G. Identification, purification, and cloning of a polypeptide (PRTF/GRM) that binds to mating-specific promoter elements in yeast. Genes Dev. 1990 Feb;4(2):299–312. doi: 10.1101/gad.4.2.299. [DOI] [PubMed] [Google Scholar]
  2. Atcheson C. L., DiDomenico B., Frackman S., Esposito R. E., Elder R. T. Isolation, DNA sequence, and regulation of a meiosis-specific eukaryotic recombination gene. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8035–8039. doi: 10.1073/pnas.84.22.8035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bender A., Sprague G. F., Jr MAT alpha 1 protein, a yeast transcription activator, binds synergistically with a second protein to a set of cell-type-specific genes. Cell. 1987 Aug 28;50(5):681–691. doi: 10.1016/0092-8674(87)90326-6. [DOI] [PubMed] [Google Scholar]
  4. Boeke J. D., Trueheart J., Natsoulis G., Fink G. R. 5-Fluoroorotic acid as a selective agent in yeast molecular genetics. Methods Enzymol. 1987;154:164–175. doi: 10.1016/0076-6879(87)54076-9. [DOI] [PubMed] [Google Scholar]
  5. Diamond M. I., Miner J. N., Yoshinaga S. K., Yamamoto K. R. Transcription factor interactions: selectors of positive or negative regulation from a single DNA element. Science. 1990 Sep 14;249(4974):1266–1272. doi: 10.1126/science.2119054. [DOI] [PubMed] [Google Scholar]
  6. Durrin L. K., Mann R. K., Kayne P. S., Grunstein M. Yeast histone H4 N-terminal sequence is required for promoter activation in vivo. Cell. 1991 Jun 14;65(6):1023–1031. doi: 10.1016/0092-8674(91)90554-c. [DOI] [PubMed] [Google Scholar]
  7. Gaber R. F., Styles C. A., Fink G. R. TRK1 encodes a plasma membrane protein required for high-affinity potassium transport in Saccharomyces cerevisiae. Mol Cell Biol. 1988 Jul;8(7):2848–2859. doi: 10.1128/mcb.8.7.2848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Guarente L., Yocum R. R., Gifford P. A GAL10-CYC1 hybrid yeast promoter identifies the GAL4 regulatory region as an upstream site. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7410–7414. doi: 10.1073/pnas.79.23.7410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Han M., Grunstein M. Nucleosome loss activates yeast downstream promoters in vivo. Cell. 1988 Dec 23;55(6):1137–1145. doi: 10.1016/0092-8674(88)90258-9. [DOI] [PubMed] [Google Scholar]
  10. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  11. Herskowitz I. A regulatory hierarchy for cell specialization in yeast. Nature. 1989 Dec 14;342(6251):749–757. doi: 10.1038/342749a0. [DOI] [PubMed] [Google Scholar]
  12. Herskowitz I. Life cycle of the budding yeast Saccharomyces cerevisiae. Microbiol Rev. 1988 Dec;52(4):536–553. doi: 10.1128/mr.52.4.536-553.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hicks J. B., Herskowitz I. Evidence for a new diffusible element of mating pheromones in yeast. Nature. 1976 Mar 18;260(5548):246–248. doi: 10.1038/260246a0. [DOI] [PubMed] [Google Scholar]
  14. Hieter P., Pridmore D., Hegemann J. H., Thomas M., Davis R. W., Philippsen P. Functional selection and analysis of yeast centromeric DNA. Cell. 1985 Oct;42(3):913–921. doi: 10.1016/0092-8674(85)90287-9. [DOI] [PubMed] [Google Scholar]
  15. Hirano T., Kinoshita N., Morikawa K., Yanagida M. Snap helix with knob and hole: essential repeats in S. pombe nuclear protein nuc2+. Cell. 1990 Jan 26;60(2):319–328. doi: 10.1016/0092-8674(90)90746-2. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Jarvis E. E., Clark K. L., Sprague G. F., Jr The yeast transcription activator PRTF, a homolog of the mammalian serum response factor, is encoded by the MCM1 gene. Genes Dev. 1989 Jul;3(7):936–945. doi: 10.1101/gad.3.7.936. [DOI] [PubMed] [Google Scholar]
  18. Johnson A. D., Herskowitz I. A repressor (MAT alpha 2 Product) and its operator control expression of a set of cell type specific genes in yeast. Cell. 1985 Aug;42(1):237–247. doi: 10.1016/s0092-8674(85)80119-7. [DOI] [PubMed] [Google Scholar]
  19. Johnson P. F., McKnight S. L. Eukaryotic transcriptional regulatory proteins. Annu Rev Biochem. 1989;58:799–839. doi: 10.1146/annurev.bi.58.070189.004055. [DOI] [PubMed] [Google Scholar]
  20. Jonat C., Rahmsdorf H. J., Park K. K., Cato A. C., Gebel S., Ponta H., Herrlich P. Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell. 1990 Sep 21;62(6):1189–1204. doi: 10.1016/0092-8674(90)90395-u. [DOI] [PubMed] [Google Scholar]
  21. Keleher C. A., Goutte C., Johnson A. D. The yeast cell-type-specific repressor alpha 2 acts cooperatively with a non-cell-type-specific protein. Cell. 1988 Jun 17;53(6):927–936. doi: 10.1016/s0092-8674(88)90449-7. [DOI] [PubMed] [Google Scholar]
  22. Klapholz S., Esposito R. E. Recombination and chromosome segregation during the single division meiosis in SPO12-1 and SPO13-1 diploids. Genetics. 1980 Nov;96(3):589–611. doi: 10.1093/genetics/96.3.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ko C. H., Buckley A. M., Gaber R. F. TRK2 is required for low affinity K+ transport in Saccharomyces cerevisiae. Genetics. 1990 Jun;125(2):305–312. doi: 10.1093/genetics/125.2.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ko C. H., Gaber R. F. TRK1 and TRK2 encode structurally related K+ transporters in Saccharomyces cerevisiae. Mol Cell Biol. 1991 Aug;11(8):4266–4273. doi: 10.1128/mcb.11.8.4266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kramer R. A., Andersen N. Isolation of yeast genes with mRNA levels controlled by phosphate concentration. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6541–6545. doi: 10.1073/pnas.77.11.6541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kronstad J. W., Holly J. A., MacKay V. L. A yeast operator overlaps an upstream activation site. Cell. 1987 Jul 31;50(3):369–377. doi: 10.1016/0092-8674(87)90491-0. [DOI] [PubMed] [Google Scholar]
  27. MacKay V. L., Welch S. K., Insley M. Y., Manney T. R., Holly J., Saari G. C., Parker M. L. The Saccharomyces cerevisiae BAR1 gene encodes an exported protein with homology to pepsin. Proc Natl Acad Sci U S A. 1988 Jan;85(1):55–59. doi: 10.1073/pnas.85.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. McCaffrey G., Clay F. J., Kelsay K., Sprague G. F., Jr Identification and regulation of a gene required for cell fusion during mating of the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1987 Aug;7(8):2680–2690. doi: 10.1128/mcb.7.8.2680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mitchell A. P., Herskowitz I. Activation of meiosis and sporulation by repression of the RME1 product in yeast. 1986 Feb 27-Mar 5Nature. 319(6056):738–742. doi: 10.1038/319738a0. [DOI] [PubMed] [Google Scholar]
  30. Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
  31. Mortimer R. K., Schild D., Contopoulou C. R., Kans J. A. Genetic map of Saccharomyces cerevisiae, edition 10. Yeast. 1989 Sep-Oct;5(5):321–403. doi: 10.1002/yea.320050503. [DOI] [PubMed] [Google Scholar]
  32. Murre C., McCaw P. S., Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989 Mar 10;56(5):777–783. doi: 10.1016/0092-8674(89)90682-x. [DOI] [PubMed] [Google Scholar]
  33. Murre C., McCaw P. S., Vaessin H., Caudy M., Jan L. Y., Jan Y. N., Cabrera C. V., Buskin J. N., Hauschka S. D., Lassar A. B. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989 Aug 11;58(3):537–544. doi: 10.1016/0092-8674(89)90434-0. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Passmore S., Elble R., Tye B. K. A protein involved in minichromosome maintenance in yeast binds a transcriptional enhancer conserved in eukaryotes. Genes Dev. 1989 Jul;3(7):921–935. doi: 10.1101/gad.3.7.921. [DOI] [PubMed] [Google Scholar]
  36. Passmore S., Maine G. T., Elble R., Christ C., Tye B. K. Saccharomyces cerevisiae protein involved in plasmid maintenance is necessary for mating of MAT alpha cells. J Mol Biol. 1988 Dec 5;204(3):593–606. doi: 10.1016/0022-2836(88)90358-0. [DOI] [PubMed] [Google Scholar]
  37. Percival-Smith A., Segall J. Isolation of DNA sequences preferentially expressed during sporulation in Saccharomyces cerevisiae. Mol Cell Biol. 1984 Jan;4(1):142–150. doi: 10.1128/mcb.4.1.142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Ptashne M. How eukaryotic transcriptional activators work. Nature. 1988 Oct 20;335(6192):683–689. doi: 10.1038/335683a0. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Schüle R., Rangarajan P., Kliewer S., Ransone L. J., Bolado J., Yang N., Verma I. M., Evans R. M. Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell. 1990 Sep 21;62(6):1217–1226. doi: 10.1016/0092-8674(90)90397-w. [DOI] [PubMed] [Google Scholar]
  42. Sikorski R. S., Boguski M. S., Goebl M., Hieter P. A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis. Cell. 1990 Jan 26;60(2):307–317. doi: 10.1016/0092-8674(90)90745-z. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. Sprague G. F., Jr, Jensen R., Herskowitz I. Control of yeast cell type by the mating type locus: positive regulation of the alpha-specific STE3 gene by the MAT alpha 1 product. Cell. 1983 Feb;32(2):409–415. doi: 10.1016/0092-8674(83)90460-9. [DOI] [PubMed] [Google Scholar]
  45. 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]
  46. Strathern J. N., Klar A. J., Hicks J. B., Abraham J. A., Ivy J. M., Nasmyth K. A., McGill C. Homothallic switching of yeast mating type cassettes is initiated by a double-stranded cut in the MAT locus. Cell. 1982 Nov;31(1):183–192. doi: 10.1016/0092-8674(82)90418-4. [DOI] [PubMed] [Google Scholar]
  47. Strich R., Slater M. R., Esposito R. E. Identification of negative regulatory genes that govern the expression of early meiotic genes in yeast. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10018–10022. doi: 10.1073/pnas.86.24.10018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. To-E A., Ueda Y., Kakimoto S. I., Oshima Y. Isolation and characterization of acid phosphatase mutants in Saccharomyces cerevisiae. J Bacteriol. 1973 Feb;113(2):727–738. doi: 10.1128/jb.113.2.727-738.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Toh-e A., Shimauchi T. Cloning and sequencing of the PHO80 gene and CEN15 of Saccharomyces cerevisiae. Yeast. 1986 Jun;2(2):129–139. doi: 10.1002/yea.320020209. [DOI] [PubMed] [Google Scholar]
  50. Trueheart J., Boeke J. D., Fink G. R. Two genes required for cell fusion during yeast conjugation: evidence for a pheromone-induced surface protein. Mol Cell Biol. 1987 Jul;7(7):2316–2328. doi: 10.1128/mcb.7.7.2316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Vidal M., Buckley A. M., Hilger F., Gaber R. F. Direct selection for mutants with increased K+ transport in Saccharomyces cerevisiae. Genetics. 1990 Jun;125(2):313–320. doi: 10.1093/genetics/125.2.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Vidal M., Gaber R. F. RPD3 encodes a second factor required to achieve maximum positive and negative transcriptional states in Saccharomyces cerevisiae. Mol Cell Biol. 1991 Dec;11(12):6317–6327. doi: 10.1128/mcb.11.12.6317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Wang H. T., Frackman S., Kowalisyn J., Esposito R. E., Elder R. Developmental regulation of SPO13, a gene required for separation of homologous chromosomes at meiosis I. Mol Cell Biol. 1987 Apr;7(4):1425–1435. doi: 10.1128/mcb.7.4.1425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Wang H., Clark I., Nicholson P. R., Herskowitz I., Stillman D. J. The Saccharomyces cerevisiae SIN3 gene, a negative regulator of HO, contains four paired amphipathic helix motifs. Mol Cell Biol. 1990 Nov;10(11):5927–5936. doi: 10.1128/mcb.10.11.5927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Wang H., Nicholson P. R., Stillman D. J. Identification of a Saccharomyces cerevisiae DNA-binding protein involved in transcriptional regulation. Mol Cell Biol. 1990 Apr;10(4):1743–1753. doi: 10.1128/mcb.10.4.1743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Wang H., Stillman D. J. In vitro regulation of a SIN3-dependent DNA-binding activity by stimulatory and inhibitory factors. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9761–9765. doi: 10.1073/pnas.87.24.9761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Yang-Yen H. F., Chambard J. C., Sun Y. L., Smeal T., Schmidt T. J., Drouin J., Karin M. Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell. 1990 Sep 21;62(6):1205–1215. doi: 10.1016/0092-8674(90)90396-v. [DOI] [PubMed] [Google Scholar]
  58. Yocum R. R., Hanley S., West R., Jr, Ptashne M. Use of lacZ fusions to delimit regulatory elements of the inducible divergent GAL1-GAL10 promoter in Saccharomyces cerevisiae. Mol Cell Biol. 1984 Oct;4(10):1985–1998. doi: 10.1128/mcb.4.10.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]

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