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. 1992 Sep;132(1):63–73. doi: 10.1093/genetics/132.1.63

Possible Cross-Regulation of Phosphate and Sulfate Metabolism in Saccharomyces Cerevisiae

K F O'Connell 1, R E Baker 1
PMCID: PMC1205130  PMID: 1398064

Abstract

CP1 (encoded by the gene CEP1) is a sequence-specific DNA binding protein of Saccharomyces cerevisiae that recognizes a sequence element (CDEI) found in both yeast centromeres and gene promoters. Strains lacking CP1 exhibit defects in growth, chromosome segregation and methionine biosynthesis. A YEp24-based yeast genomic library was screened for plasmids which suppressed the methionine auxotrophy of a cep1 null mutant. The suppressing plasmids contained either CEP1 or DNA derived from the PH04 locus. Subcloning experiments confirmed that suppression correlated with increased dosage of PHO4. PHO4(c), pho80 and pho84 mutations, all of which lead to constitutive activation of the PHO4 transcription factor, also suppressed cep1 methionine auxotrophy. The suppression appeared to be a direct effect of PHO4, not a secondary effect of PHO regulon derepression, and was PHO2-dependent. Spontaneously arising extragenic suppressors of cep1 methionine auxotrophy were also isolated; approximately one-third of them were alleles of pho80. While PHO4 overexpression suppressed the methionine auxotrophy of a cep1 mutant, CEP1 overexpression failed to suppress the phenotype of a pho4 mutant; however, a cep1 null mutation suppressed the low inorganic phosphate growth deficiency of a pho84 mutant. The results may suggest that phosphate and sulfate metabolism are cross-regulated.

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Selected References

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  1. Baker R. E., Masison D. C. Isolation of the gene encoding the Saccharomyces cerevisiae centromere-binding protein CP1. Mol Cell Biol. 1990 Jun;10(6):2458–2467. doi: 10.1128/mcb.10.6.2458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benezra R., Davis R. L., Lockshon D., Turner D. L., Weintraub H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell. 1990 Apr 6;61(1):49–59. doi: 10.1016/0092-8674(90)90214-y. [DOI] [PubMed] [Google Scholar]
  3. Berben G., Legrain M., Gilliquet V., Hilger F. The yeast regulatory gene PHO4 encodes a helix-loop-helix motif. Yeast. 1990 Sep-Oct;6(5):451–454. doi: 10.1002/yea.320060510. [DOI] [PubMed] [Google Scholar]
  4. Bergman L. W. A DNA fragment containing the upstream activator sequence determines nucleosome positioning of the transcriptionally repressed PHO5 gene of Saccharomyces cerevisiae. Mol Cell Biol. 1986 Jul;6(7):2298–2304. doi: 10.1128/mcb.6.7.2298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Boeke J. D., LaCroute F., Fink G. R. A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Mol Gen Genet. 1984;197(2):345–346. doi: 10.1007/BF00330984. [DOI] [PubMed] [Google Scholar]
  7. Bram R. J., Kornberg R. D. Isolation of a Saccharomyces cerevisiae centromere DNA-binding protein, its human homolog, and its possible role as a transcription factor. Mol Cell Biol. 1987 Jan;7(1):403–409. doi: 10.1128/mcb.7.1.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Braun T., Winter B., Bober E., Arnold H. H. Transcriptional activation domain of the muscle-specific gene-regulatory protein myf5. Nature. 1990 Aug 16;346(6285):663–665. doi: 10.1038/346663a0. [DOI] [PubMed] [Google Scholar]
  9. Breton A., Surdin-Kerjan Y. Sulfate uptake in Saccharomyces cerevisiae: biochemical and genetic study. J Bacteriol. 1977 Oct;132(1):224–232. doi: 10.1128/jb.132.1.224-232.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Buchman A. R., Kimmerly W. J., Rine J., Kornberg R. D. Two DNA-binding factors recognize specific sequences at silencers, upstream activating sequences, autonomously replicating sequences, and telomeres in Saccharomyces cerevisiae. Mol Cell Biol. 1988 Jan;8(1):210–225. doi: 10.1128/mcb.8.1.210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Buchman A. R., Kornberg R. D. A yeast ARS-binding protein activates transcription synergistically in combination with other weak activating factors. Mol Cell Biol. 1990 Mar;10(3):887–897. doi: 10.1128/mcb.10.3.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Bun-Ya M., Nishimura M., Harashima S., Oshima Y. The PHO84 gene of Saccharomyces cerevisiae encodes an inorganic phosphate transporter. Mol Cell Biol. 1991 Jun;11(6):3229–3238. doi: 10.1128/mcb.11.6.3229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cai M. J., Davis R. W. Purification of a yeast centromere-binding protein that is able to distinguish single base-pair mutations in its recognition site. Mol Cell Biol. 1989 Jun;9(6):2544–2550. doi: 10.1128/mcb.9.6.2544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Carlson M., Botstein D. Two differentially regulated mRNAs with different 5' ends encode secreted with intracellular forms of yeast invertase. Cell. 1982 Jan;28(1):145–154. doi: 10.1016/0092-8674(82)90384-1. [DOI] [PubMed] [Google Scholar]
  15. Cherest H., Thomas D., Surdin-Kerjan Y. Nucleotide sequence of the MET8 gene of Saccharomyces cerevisiae. Nucleic Acids Res. 1990 Feb 11;18(3):659–659. doi: 10.1093/nar/18.3.659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Cumberledge S., Carbon J. Mutational analysis of meiotic and mitotic centromere function in Saccharomyces cerevisiae. Genetics. 1987 Oct;117(2):203–212. doi: 10.1093/genetics/117.2.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dang C. V., Dolde C., Gillison M. L., Kato G. J. Discrimination between related DNA sites by a single amino acid residue of Myc-related basic-helix-loop-helix proteins. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):599–602. doi: 10.1073/pnas.89.2.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Davis R. L., Cheng P. F., Lassar A. B., Weintraub H. The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation. Cell. 1990 Mar 9;60(5):733–746. doi: 10.1016/0092-8674(90)90088-v. [DOI] [PubMed] [Google Scholar]
  19. Densmore L., Payne W. E., Fitzgerald-Hayes M. In vivo genomic footprint of a yeast centromere. Mol Cell Biol. 1991 Jan;11(1):154–165. doi: 10.1128/mcb.11.1.154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Dorsman J. C., van Heeswijk W. C., Grivell L. A. Identification of two factors which bind to the upstream sequences of a number of nuclear genes coding for mitochondrial proteins and to genetic elements important for cell division in yeast. Nucleic Acids Res. 1988 Aug 11;16(15):7287–7301. doi: 10.1093/nar/16.15.7287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Fisher F., Jayaraman P. S., Goding C. R. C-myc and the yeast transcription factor PHO4 share a common CACGTG-binding motif. Oncogene. 1991 Jul;6(7):1099–1104. [PubMed] [Google Scholar]
  22. Gaudet A., Fitzgerald-Hayes M. Mutations in CEN3 cause aberrant chromosome segregation during meiosis in Saccharomyces cerevisiae. Genetics. 1989 Mar;121(3):477–489. doi: 10.1093/genetics/121.3.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gregor P. D., Sawadogo M., Roeder R. G. The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Genes Dev. 1990 Oct;4(10):1730–1740. doi: 10.1101/gad.4.10.1730. [DOI] [PubMed] [Google Scholar]
  24. Hegemann J. H., Shero J. H., Cottarel G., Philippsen P., Hieter P. Mutational analysis of centromere DNA from chromosome VI of Saccharomyces cerevisiae. Mol Cell Biol. 1988 Jun;8(6):2523–2535. doi: 10.1128/mcb.8.6.2523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Hill J. E., Myers A. M., Koerner T. J., Tzagoloff A. Yeast/E. coli shuttle vectors with multiple unique restriction sites. Yeast. 1986 Sep;2(3):163–167. doi: 10.1002/yea.320020304. [DOI] [PubMed] [Google Scholar]
  27. Hu Y. F., Lüscher B., Admon A., Mermod N., Tjian R. Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. Genes Dev. 1990 Oct;4(10):1741–1752. doi: 10.1101/gad.4.10.1741. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Ju Q. D., Morrow B. E., Warner J. R. REB1, a yeast DNA-binding protein with many targets, is essential for growth and bears some resemblance to the oncogene myb. Mol Cell Biol. 1990 Oct;10(10):5226–5234. doi: 10.1128/mcb.10.10.5226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Korch C., Mountain H. A., Byström A. S. Cloning, nucleotide sequence, and regulation of MET14, the gene encoding the APS kinase of Saccharomyces cerevisiae. Mol Gen Genet. 1991 Sep;229(1):96–108. doi: 10.1007/BF00264218. [DOI] [PubMed] [Google Scholar]
  31. Mellor J., Jiang W., Funk M., Rathjen J., Barnes C. A., Hinz T., Hegemann J. H., Philippsen P. CPF1, a yeast protein which functions in centromeres and promoters. EMBO J. 1990 Dec;9(12):4017–4026. doi: 10.1002/j.1460-2075.1990.tb07623.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mellor J., Rathjen J., Jiang W., Barnes C. A., Dowell S. J. DNA binding of CPF1 is required for optimal centromere function but not for maintaining methionine prototrophy in yeast. Nucleic Acids Res. 1991 Jun 11;19(11):2961–2969. doi: 10.1093/nar/19.11.2961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. Ogawa N., Oshima Y. Functional domains of a positive regulatory protein, PHO4, for transcriptional control of the phosphatase regulon in Saccharomyces cerevisiae. Mol Cell Biol. 1990 May;10(5):2224–2236. doi: 10.1128/mcb.10.5.2224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Parker R., Jacobson A. Translation and a 42-nucleotide segment within the coding region of the mRNA encoded by the MAT alpha 1 gene are involved in promoting rapid mRNA decay in yeast. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2780–2784. doi: 10.1073/pnas.87.7.2780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rothstein R. J. One-step gene disruption in yeast. Methods Enzymol. 1983;101:202–211. doi: 10.1016/0076-6879(83)01015-0. [DOI] [PubMed] [Google Scholar]
  38. Rubin G. M. Three forms of the 5.8-S ribosomal RNA species in Saccharomyces cerevisiae. Eur J Biochem. 1974 Jan 3;41(1):197–202. doi: 10.1111/j.1432-1033.1974.tb03260.x. [DOI] [PubMed] [Google Scholar]
  39. Schiestl R. H., Gietz R. D. High efficiency transformation of intact yeast cells using single stranded nucleic acids as a carrier. Curr Genet. 1989 Dec;16(5-6):339–346. doi: 10.1007/BF00340712. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. Sun X. H., Baltimore D. An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers. Cell. 1991 Jan 25;64(2):459–470. doi: 10.1016/0092-8674(91)90653-g. [DOI] [PubMed] [Google Scholar]
  42. Tamai Y., Toh-e A., Oshima Y. Regulation of inorganic phosphate transport systems in Saccharomyces cerevisiae. J Bacteriol. 1985 Nov;164(2):964–968. doi: 10.1128/jb.164.2.964-968.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Thomas D., Barbey R., Surdin-Kerjan Y. Gene-enzyme relationship in the sulfate assimilation pathway of Saccharomyces cerevisiae. Study of the 3'-phosphoadenylylsulfate reductase structural gene. J Biol Chem. 1990 Sep 15;265(26):15518–15524. [PubMed] [Google Scholar]
  44. Thomas D., Cherest H., Surdin-Kerjan Y. Elements involved in S-adenosylmethionine-mediated regulation of the Saccharomyces cerevisiae MET25 gene. Mol Cell Biol. 1989 Aug;9(8):3292–3298. doi: 10.1128/mcb.9.8.3292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Thomas D., Jacquemin I., Surdin-Kerjan Y. MET4, a leucine zipper protein, and centromere-binding factor 1 are both required for transcriptional activation of sulfur metabolism in Saccharomyces cerevisiae. Mol Cell Biol. 1992 Apr;12(4):1719–1727. doi: 10.1128/mcb.12.4.1719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Toh-E A., Oshima Y. Characterization of a dominant, constitutive mutation, PHOO, for the repressible acid phosphatase synthesis in Saccharomyces cerevisiae. J Bacteriol. 1974 Nov;120(2):608–617. doi: 10.1128/jb.120.2.608-617.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Vogel K., Hinnen A. The yeast phosphatase system. Mol Microbiol. 1990 Dec;4(12):2013–2017. doi: 10.1111/j.1365-2958.1990.tb00560.x. [DOI] [PubMed] [Google Scholar]
  48. 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]

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