Skip to main content
NCBI home page
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1997 Sep;179(17):5609–5613. doi: 10.1128/jb.179.17.5609-5613.1997

Nitrogen GATA factors participate in transcriptional regulation of vacuolar protease genes in Saccharomyces cerevisiae.

J A Coffman 1, T G Cooper 1
PMCID: PMC179439  PMID: 9287023

Abstract

The expression of most nitrogen catabolic genes in Saccharomyces cerevisiae is regulated at the level of transcription in response to the quality of nitrogen source available. This regulation is accomplished through four GATA-family transcription factors: two positively acting factors capable of transcriptional activation (Gln3p and Gat1p) and two negatively acting factors capable of down-regulating Gln3p- and/or Gat1p-dependent transcription (Dal80p and Deh1p). Current understanding of nitrogen-responsive transcriptional regulation is the result of extensive analysis of genes required for the catabolism of small molecules, e.g., amino acids, allantoin, or ammonia. However, cells contain another, equally important source of nitrogen, intracellular protein, which undergoes rapid turnover during special circumstances such as entry into stationary phase, and during sporulation. Here we show that the expression of some (CPS1, PEP4, PRB1, and LAP4) but not all (PRC1) vacuolar protease genes is nitrogen catabolite repression sensitive and is regulated by the GATA-family proteins Gln3p, Gat1p, and Dal80p. These observations extend the global participation of GATA-family transcription factors to include not only well-studied genes associated with the catabolism of small nitrogenous compounds but also genes whose products are responsible for the turnover of intracellular macromolecules. They also point to the usefulness of considering control of the nitrogen-responsive GATA factors when studying the regulation of the protein turnover machinery.

Full Text

The Full Text of this article is available as a PDF (508.8 KB).

Selected References

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

  1. André B., Talibi D., Soussi Boudekou S., Hein C., Vissers S., Coornaert D. Two mutually exclusive regulatory systems inhibit UASGATA, a cluster of 5'-GAT(A/T)A-3' upstream from the UGA4 gene of Saccharomyces cerevisiae. Nucleic Acids Res. 1995 Feb 25;23(4):558–564. doi: 10.1093/nar/23.4.558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arceci R. J., King A. A., Simon M. C., Orkin S. H., Wilson D. B. Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart. Mol Cell Biol. 1993 Apr;13(4):2235–2246. doi: 10.1128/mcb.13.4.2235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blinder D., Coschigano P. W., Magasanik B. Interaction of the GATA factor Gln3p with the nitrogen regulator Ure2p in Saccharomyces cerevisiae. J Bacteriol. 1996 Aug;178(15):4734–4736. doi: 10.1128/jb.178.15.4734-4736.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blinder D., Magasanik B. Recognition of nitrogen-responsive upstream activation sequences of Saccharomyces cerevisiae by the product of the GLN3 gene. J Bacteriol. 1995 Jul;177(14):4190–4193. doi: 10.1128/jb.177.14.4190-4193.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bordallo J., Bordallo C., Gascón S., Suárez-Rendueles P. Molecular cloning and sequencing of genomic DNA encoding yeast vacuolar carboxypeptidase yscS. FEBS Lett. 1991 May 20;283(1):27–32. doi: 10.1016/0014-5793(91)80546-f. [DOI] [PubMed] [Google Scholar]
  6. Bordallo J., Suárez-Rendueles P. Control of Saccharomyces cerevisiae carboxypeptidase S (CPS1) gene expression under nutrient limitation. Yeast. 1993 Apr;9(4):339–349. doi: 10.1002/yea.320090404. [DOI] [PubMed] [Google Scholar]
  7. Bysani N., Daugherty J. R., Cooper T. G. Saturation mutagenesis of the UASNTR (GATAA) responsible for nitrogen catabolite repression-sensitive transcriptional activation of the allantoin pathway genes in Saccharomyces cerevisiae. J Bacteriol. 1991 Aug;173(16):4977–4982. doi: 10.1128/jb.173.16.4977-4982.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Chang Y. H., Smith J. A. Molecular cloning and sequencing of genomic DNA encoding aminopeptidase I from Saccharomyces cerevisiae. J Biol Chem. 1989 Apr 25;264(12):6979–6983. [PubMed] [Google Scholar]
  10. Chisholm G., Cooper T. G. Isolation and characterization of mutants that produce the allantoin-degrading enzymes constitutively in Saccharomyces cerevisiae. Mol Cell Biol. 1982 Sep;2(9):1088–1095. doi: 10.1128/mcb.2.9.1088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Coffman J. A., Rai R., Cooper T. G. Genetic evidence for Gln3p-independent, nitrogen catabolite repression-sensitive gene expression in Saccharomyces cerevisiae. J Bacteriol. 1995 Dec;177(23):6910–6918. doi: 10.1128/jb.177.23.6910-6918.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Coffman J. A., Rai R., Cunningham T., Svetlov V., Cooper T. G. Gat1p, a GATA family protein whose production is sensitive to nitrogen catabolite repression, participates in transcriptional activation of nitrogen-catabolic genes in Saccharomyces cerevisiae. Mol Cell Biol. 1996 Mar;16(3):847–858. doi: 10.1128/mcb.16.3.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Coffman J. A., Rai R., Loprete D. M., Cunningham T., Svetlov V., Cooper T. G. Cross regulation of four GATA factors that control nitrogen catabolic gene expression in Saccharomyces cerevisiae. J Bacteriol. 1997 Jun;179(11):3416–3429. doi: 10.1128/jb.179.11.3416-3429.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Coffman J. A., el Berry H. M., Cooper T. G. The URE2 protein regulates nitrogen catabolic gene expression through the GATAA-containing UASNTR element in Saccharomyces cerevisiae. J Bacteriol. 1994 Dec;176(24):7476–7483. doi: 10.1128/jb.176.24.7476-7483.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cooper T. G., Ferguson D., Rai R., Bysani N. The GLN3 gene product is required for transcriptional activation of allantoin system gene expression in Saccharomyces cerevisiae. J Bacteriol. 1990 Feb;172(2):1014–1018. doi: 10.1128/jb.172.2.1014-1018.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Cooper T. G., Rai R., Yoo H. S. Requirement of upstream activation sequences for nitrogen catabolite repression of the allantoin system genes in Saccharomyces cerevisiae. Mol Cell Biol. 1989 Dec;9(12):5440–5444. doi: 10.1128/mcb.9.12.5440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Coornaert D., Vissers S., André B., Grenson M. The UGA43 negative regulatory gene of Saccharomyces cerevisiae contains both a GATA-1 type zinc finger and a putative leucine zipper. Curr Genet. 1992 Apr;21(4-5):301–307. doi: 10.1007/BF00351687. [DOI] [PubMed] [Google Scholar]
  18. Coschigano P. W., Magasanik B. The URE2 gene product of Saccharomyces cerevisiae plays an important role in the cellular response to the nitrogen source and has homology to glutathione s-transferases. Mol Cell Biol. 1991 Feb;11(2):822–832. doi: 10.1128/mcb.11.2.822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Courchesne W. E., Magasanik B. Regulation of nitrogen assimilation in Saccharomyces cerevisiae: roles of the URE2 and GLN3 genes. J Bacteriol. 1988 Feb;170(2):708–713. doi: 10.1128/jb.170.2.708-713.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Cueva R., García-Alvarez N., Suárez-Rendueles P. Yeast vacuolar aminopeptidase yscI. Isolation and regulation of the APE1 (LAP4) structural gene. FEBS Lett. 1989 Dec 18;259(1):125–129. doi: 10.1016/0014-5793(89)81510-8. [DOI] [PubMed] [Google Scholar]
  21. Cunningham T. S., Cooper T. G. Expression of the DAL80 gene, whose product is homologous to the GATA factors and is a negative regulator of multiple nitrogen catabolic genes in Saccharomyces cerevisiae, is sensitive to nitrogen catabolite repression. Mol Cell Biol. 1991 Dec;11(12):6205–6215. doi: 10.1128/mcb.11.12.6205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Cunningham T. S., Cooper T. G. The Saccharomyces cerevisiae DAL80 repressor protein binds to multiple copies of GATAA-containing sequences (URSGATA). J Bacteriol. 1993 Sep;175(18):5851–5861. doi: 10.1128/jb.175.18.5851-5861.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Cunningham T. S., Dorrington R. A., Cooper T. G. The UGA4 UASNTR site required for GLN3-dependent transcriptional activation also mediates DAL80-responsive regulation and DAL80 protein binding in Saccharomyces cerevisiae. J Bacteriol. 1994 Aug;176(15):4718–4725. doi: 10.1128/jb.176.15.4718-4725.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Cunningham T. S., Svetlov V. V., Rai R., Smart W., Cooper T. G. G1n3p is capable of binding to UAS(NTR) elements and activating transcription in Saccharomyces cerevisiae. J Bacteriol. 1996 Jun;178(12):3470–3479. doi: 10.1128/jb.178.12.3470-3479.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Daugherty J. R., Rai R., el Berry H. M., Cooper T. G. Regulatory circuit for responses of nitrogen catabolic gene expression to the GLN3 and DAL80 proteins and nitrogen catabolite repression in Saccharomyces cerevisiae. J Bacteriol. 1993 Jan;175(1):64–73. doi: 10.1128/jb.175.1.64-73.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Evans T., Felsenfeld G. The erythroid-specific transcription factor Eryf1: a new finger protein. Cell. 1989 Sep 8;58(5):877–885. doi: 10.1016/0092-8674(89)90940-9. [DOI] [PubMed] [Google Scholar]
  27. Fu Y. H., Marzluf G. A. nit-2, the major positive-acting nitrogen regulatory gene of Neurospora crassa, encodes a sequence-specific DNA-binding protein. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5331–5335. doi: 10.1073/pnas.87.14.5331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J. C., Coster F., Cziepluch C., De Haan M., Domdey H. Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X. EMBO J. 1996 May 1;15(9):2031–2049. [PMC free article] [PubMed] [Google Scholar]
  29. Haas H., Bauer B., Redl B., Stöffler G., Marzluf G. A. Molecular cloning and analysis of nre, the major nitrogen regulatory gene of Penicillium chrysogenum. Curr Genet. 1995 Jan;27(2):150–158. doi: 10.1007/BF00313429. [DOI] [PubMed] [Google Scholar]
  30. Jones E. W., Zubenko G. S., Parker R. R. PEP4 gene function is required for expression of several vacuolar hydrolases in Saccharomyces cerevisiae. Genetics. 1982 Dec;102(4):665–677. doi: 10.1093/genetics/102.4.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kaneko Y., Toh-e A., Oshima Y. Identification of the genetic locus for the structural gene and a new regulatory gene for the synthesis of repressible alkaline phosphatase in Saccharomyces cerevisiae. Mol Cell Biol. 1982 Feb;2(2):127–137. doi: 10.1128/mcb.2.2.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Minehart P. L., Magasanik B. Sequence and expression of GLN3, a positive nitrogen regulatory gene of Saccharomyces cerevisiae encoding a protein with a putative zinc finger DNA-binding domain. Mol Cell Biol. 1991 Dec;11(12):6216–6228. doi: 10.1128/mcb.11.12.6216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Minehart P. L., Magasanik B. Sequence of the GLN1 gene of Saccharomyces cerevisiae: role of the upstream region in regulation of glutamine synthetase expression. J Bacteriol. 1992 Mar;174(6):1828–1836. doi: 10.1128/jb.174.6.1828-1836.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Mitchell A. P., Magasanik B. Regulation of glutamine-repressible gene products by the GLN3 function in Saccharomyces cerevisiae. Mol Cell Biol. 1984 Dec;4(12):2758–2766. doi: 10.1128/mcb.4.12.2758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Moehle C. M., Aynardi M. W., Kolodny M. R., Park F. J., Jones E. W. Protease B of Saccharomyces cerevisiae: isolation and regulation of the PRB1 structural gene. Genetics. 1987 Feb;115(2):255–263. doi: 10.1093/genetics/115.2.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Naik R. R., Nebes V., Jones E. W. Regulation of the proteinase B structural gene PRB1 in Saccharomyces cerevisiae. J Bacteriol. 1997 Mar;179(5):1469–1474. doi: 10.1128/jb.179.5.1469-1474.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Omichinski J. G., Clore G. M., Schaad O., Felsenfeld G., Trainor C., Appella E., Stahl S. J., Gronenborn A. M. NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1. Science. 1993 Jul 23;261(5120):438–446. doi: 10.1126/science.8332909. [DOI] [PubMed] [Google Scholar]
  38. Platt A., Langdon T., Arst H. N., Jr, Kirk D., Tollervey D., Sanchez J. M., Caddick M. X. Nitrogen metabolite signalling involves the C-terminus and the GATA domain of the Aspergillus transcription factor AREA and the 3' untranslated region of its mRNA. EMBO J. 1996 Jun 3;15(11):2791–2801. [PMC free article] [PubMed] [Google Scholar]
  39. Rai R., Genbauffe F. S., Cooper T. G. Structure and transcription of the allantoate permease gene (DAL5) from Saccharomyces cerevisiae. J Bacteriol. 1988 Jan;170(1):266–271. doi: 10.1128/jb.170.1.266-271.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rai R., Genbauffe F. S., Sumrada R. A., Cooper T. G. Identification of sequences responsible for transcriptional activation of the allantoate permease gene in Saccharomyces cerevisiae. Mol Cell Biol. 1989 Feb;9(2):602–608. doi: 10.1128/mcb.9.2.602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rai R., Genbauffe F., Lea H. Z., Cooper T. G. Transcriptional regulation of the DAL5 gene in Saccharomyces cerevisiae. J Bacteriol. 1987 Aug;169(8):3521–3524. doi: 10.1128/jb.169.8.3521-3524.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Rasmussen S. W. A 37.5 kb region of yeast chromosome X includes the SME1, MEF2, GSH1 and CSD3 genes, a TCP-1-related gene, an open reading frame similar to the DAL80 gene, and a tRNA(Arg). Yeast. 1995 Jul;11(9):873–883. doi: 10.1002/yea.320110909. [DOI] [PubMed] [Google Scholar]
  43. Smith M. M., Andrésson O. S. DNA sequences of yeast H3 and H4 histone genes from two non-allelic gene sets encode identical H3 and H4 proteins. J Mol Biol. 1983 Sep 25;169(3):663–690. doi: 10.1016/s0022-2836(83)80164-8. [DOI] [PubMed] [Google Scholar]
  44. Spormann D. O., Heim J., Wolf D. H. Carboxypeptidase yscS: gene structure and function of the vacuolar enzyme. Eur J Biochem. 1991 Apr 23;197(2):399–405. doi: 10.1111/j.1432-1033.1991.tb15924.x. [DOI] [PubMed] [Google Scholar]
  45. Stanbrough M., Magasanik B. Transcriptional and posttranslational regulation of the general amino acid permease of Saccharomyces cerevisiae. J Bacteriol. 1995 Jan;177(1):94–102. doi: 10.1128/jb.177.1.94-102.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Stanbrough M., Magasanik B. Two transcription factors, Gln3p and Nil1p, use the same GATAAG sites to activate the expression of GAP1 of Saccharomyces cerevisiae. J Bacteriol. 1996 Apr;178(8):2465–2468. doi: 10.1128/jb.178.8.2465-2468.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Talibi D., Grenson M., André B. Cis- and trans-acting elements determining induction of the genes of the gamma-aminobutyrate (GABA) utilization pathway in Saccharomyces cerevisiae. Nucleic Acids Res. 1995 Feb 25;23(4):550–557. doi: 10.1093/nar/23.4.550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Trainor C. D., Evans T., Felsenfeld G., Boguski M. S. Structure and evolution of a human erythroid transcription factor. Nature. 1990 Jan 4;343(6253):92–96. doi: 10.1038/343092a0. [DOI] [PubMed] [Google Scholar]
  49. Vissers S., Andre B., Muyldermans F., Grenson M. Positive and negative regulatory elements control the expression of the UGA4 gene coding for the inducible 4-aminobutyric-acid-specific permease in Saccharomyces cerevisiae. Eur J Biochem. 1989 May 1;181(2):357–361. doi: 10.1111/j.1432-1033.1989.tb14732.x. [DOI] [PubMed] [Google Scholar]
  50. Wickner R. B. [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. Science. 1994 Apr 22;264(5158):566–569. doi: 10.1126/science.7909170. [DOI] [PubMed] [Google Scholar]
  51. Xu S., Falvey D. A., Brandriss M. C. Roles of URE2 and GLN3 in the proline utilization pathway in Saccharomyces cerevisiae. Mol Cell Biol. 1995 Apr;15(4):2321–2330. doi: 10.1128/mcb.15.4.2321. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES