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. 1996 Nov;16(11):6419–6426. doi: 10.1128/mcb.16.11.6419

Rgt1p of Saccharomyces cerevisiae, a key regulator of glucose-induced genes, is both an activator and a repressor of transcription.

S Ozcan 1, T Leong 1, M Johnston 1
PMCID: PMC231643  PMID: 8887670

Abstract

The RGT1 gene of Saccharomyces cerevisiae plays a central role in the glucose-induced expression of hexose transporter (HXT) genes. Genetic evidence suggests that it encodes a repressor of the HXT genes whose function is inhibited by glucose. Here, we report the isolation of RGT1 and demonstrate that it encodes a bifunctional transcription factor. Rgt1p displays three different transcriptional modes in response to glucose: (i) in the absence of glucose, it functions as a transcriptional repressor; (ii) high concentrations of glucose cause it to function as a transcriptional activator; and (iii) in cells growing on low levels of glucose, Rgt1p has a neutral role, neither repressing nor activating transcription. Glucose alters Rgt1p function through a pathway that includes two glucose sensors, Snf3p and Rgt2p, and Grr1p. The glucose transporter Snf3p, which appears to be a low-glucose sensor, is required for inhibition of Rgt1p repressor function by low levels of glucose. Rgt2p, a glucose transporter that functions as a high-glucose sensor, is required for conversion of Rgt1p into an activator by high levels of glucose. Grr1p, a component of the glucose signaling pathway, is required both for inactivation of Rgt1p repressor function by low levels of glucose and for conversion of Rgt1p into an activator at high levels of glucose. Thus, signals generated by two different glucose sensors act through Grr1p to determine Rgt1p function.

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Selected References

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  1. Alani E., Cao L., Kleckner N. A method for gene disruption that allows repeated use of URA3 selection in the construction of multiply disrupted yeast strains. Genetics. 1987 Aug;116(4):541–545. doi: 10.1534/genetics.112.541.test. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. André B. The UGA3 gene regulating the GABA catabolic pathway in Saccharomyces cerevisiae codes for a putative zinc-finger protein acting on RNA amount. Mol Gen Genet. 1990 Jan;220(2):269–276. doi: 10.1007/BF00260493. [DOI] [PubMed] [Google Scholar]
  3. Balasubramanian B., Lowry C. V., Zitomer R. S. The Rox1 repressor of the Saccharomyces cerevisiae hypoxic genes is a specific DNA-binding protein with a high-mobility-group motif. Mol Cell Biol. 1993 Oct;13(10):6071–6078. doi: 10.1128/mcb.13.10.6071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baudin A., Ozier-Kalogeropoulos O., Denouel A., Lacroute F., Cullin C. A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae. Nucleic Acids Res. 1993 Jul 11;21(14):3329–3330. doi: 10.1093/nar/21.14.3329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bisson L. F., Coons D. M., Kruckeberg A. L., Lewis D. A. Yeast sugar transporters. Crit Rev Biochem Mol Biol. 1993;28(4):259–308. doi: 10.3109/10409239309078437. [DOI] [PubMed] [Google Scholar]
  6. Bisson L. F., Neigeborn L., Carlson M., Fraenkel D. G. The SNF3 gene is required for high-affinity glucose transport in Saccharomyces cerevisiae. J Bacteriol. 1987 Apr;169(4):1656–1662. doi: 10.1128/jb.169.4.1656-1662.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bowdish K. S., Yuan H. E., Mitchell A. P. Positive control of yeast meiotic genes by the negative regulator UME6. Mol Cell Biol. 1995 Jun;15(6):2955–2961. doi: 10.1128/mcb.15.6.2955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brent R., Ptashne M. A eukaryotic transcriptional activator bearing the DNA specificity of a prokaryotic repressor. Cell. 1985 Dec;43(3 Pt 2):729–736. doi: 10.1016/0092-8674(85)90246-6. [DOI] [PubMed] [Google Scholar]
  9. Celenza J. L., Marshall-Carlson L., Carlson M. The yeast SNF3 gene encodes a glucose transporter homologous to the mammalian protein. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2130–2134. doi: 10.1073/pnas.85.7.2130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Coons D. M., Boulton R. B., Bisson L. F. Computer-assisted nonlinear regression analysis of the multicomponent glucose uptake kinetics of Saccharomyces cerevisiae. J Bacteriol. 1995 Jun;177(11):3251–3258. doi: 10.1128/jb.177.11.3251-3258.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Deckert J., Rodriguez Torres A. M., Simon J. T., Zitomer R. S. Mutational analysis of Rox1, a DNA-bending repressor of hypoxic genes in Saccharomyces cerevisiae. Mol Cell Biol. 1995 Nov;15(11):6109–6117. doi: 10.1128/mcb.15.11.6109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Entian K. D., Barnett J. A. Regulation of sugar utilization by Saccharomyces cerevisiae. Trends Biochem Sci. 1992 Dec;17(12):506–510. doi: 10.1016/0968-0004(92)90341-6. [DOI] [PubMed] [Google Scholar]
  13. Erickson J. R., Johnston M. Suppressors reveal two classes of glucose repression genes in the yeast Saccharomyces cerevisiae. Genetics. 1994 Apr;136(4):1271–1278. doi: 10.1093/genetics/136.4.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Flick J. S., Johnston M. GRR1 of Saccharomyces cerevisiae is required for glucose repression and encodes a protein with leucine-rich repeats. Mol Cell Biol. 1991 Oct;11(10):5101–5112. doi: 10.1128/mcb.11.10.5101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gancedo J. M. Carbon catabolite repression in yeast. Eur J Biochem. 1992 Jun 1;206(2):297–313. doi: 10.1111/j.1432-1033.1992.tb16928.x. [DOI] [PubMed] [Google Scholar]
  16. Guarente L. Yeast promoters and lacZ fusions designed to study expression of cloned genes in yeast. Methods Enzymol. 1983;101:181–191. doi: 10.1016/0076-6879(83)01013-7. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Johnston M. A model fungal gene regulatory mechanism: the GAL genes of Saccharomyces cerevisiae. Microbiol Rev. 1987 Dec;51(4):458–476. doi: 10.1128/mr.51.4.458-476.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Keleher C. A., Redd M. J., Schultz J., Carlson M., Johnson A. D. Ssn6-Tup1 is a general repressor of transcription in yeast. Cell. 1992 Feb 21;68(4):709–719. doi: 10.1016/0092-8674(92)90146-4. [DOI] [PubMed] [Google Scholar]
  20. Ko C. H., Liang H., Gaber R. F. Roles of multiple glucose transporters in Saccharomyces cerevisiae. Mol Cell Biol. 1993 Jan;13(1):638–648. doi: 10.1128/mcb.13.1.638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Komachi K., Redd M. J., Johnson A. D. The WD repeats of Tup1 interact with the homeo domain protein alpha 2. Genes Dev. 1994 Dec 1;8(23):2857–2867. doi: 10.1101/gad.8.23.2857. [DOI] [PubMed] [Google Scholar]
  22. Ma J., Ptashne M. A new class of yeast transcriptional activators. Cell. 1987 Oct 9;51(1):113–119. doi: 10.1016/0092-8674(87)90015-8. [DOI] [PubMed] [Google Scholar]
  23. Marshall-Carlson L., Celenza J. L., Laurent B. C., Carlson M. Mutational analysis of the SNF3 glucose transporter of Saccharomyces cerevisiae. Mol Cell Biol. 1990 Mar;10(3):1105–1115. doi: 10.1128/mcb.10.3.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Marshall-Carlson L., Neigeborn L., Coons D., Bisson L., Carlson M. Dominant and recessive suppressors that restore glucose transport in a yeast snf3 mutant. Genetics. 1991 Jul;128(3):505–512. doi: 10.1093/genetics/128.3.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Myers A. M., Tzagoloff A., Kinney D. M., Lusty C. J. Yeast shuttle and integrative vectors with multiple cloning sites suitable for construction of lacZ fusions. Gene. 1986;45(3):299–310. doi: 10.1016/0378-1119(86)90028-4. [DOI] [PubMed] [Google Scholar]
  26. Niedenthal R. K., Riles L., Johnston M., Hegemann J. H. Green fluorescent protein as a marker for gene expression and subcellular localization in budding yeast. Yeast. 1996 Jun 30;12(8):773–786. doi: 10.1002/(SICI)1097-0061(19960630)12:8%3C773::AID-YEA972%3E3.0.CO;2-L. [DOI] [PubMed] [Google Scholar]
  27. Niederacher D., Entian K. D. Characterization of Hex2 protein, a negative regulatory element necessary for glucose repression in yeast. Eur J Biochem. 1991 Sep 1;200(2):311–319. doi: 10.1111/j.1432-1033.1991.tb16187.x. [DOI] [PubMed] [Google Scholar]
  28. Ozcan S., Freidel K., Leuker A., Ciriacy M. Glucose uptake and catabolite repression in dominant HTR1 mutants of Saccharomyces cerevisiae. J Bacteriol. 1993 Sep;175(17):5520–5528. doi: 10.1128/jb.175.17.5520-5528.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ozcan S., Johnston M. Three different regulatory mechanisms enable yeast hexose transporter (HXT) genes to be induced by different levels of glucose. Mol Cell Biol. 1995 Mar;15(3):1564–1572. doi: 10.1128/mcb.15.3.1564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ozcan S., Johnston M. Two different repressors collaborate to restrict expression of the yeast glucose transporter genes HXT2 and HXT4 to low levels of glucose. Mol Cell Biol. 1996 Oct;16(10):5536–5545. doi: 10.1128/mcb.16.10.5536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ozcan S., Schulte F., Freidel K., Weber A., Ciriacy M. Glucose uptake and metabolism in grr1/cat80 mutants of Saccharomyces cerevisiae. Eur J Biochem. 1994 Sep 1;224(2):605–611. doi: 10.1111/j.1432-1033.1994.00605.x. [DOI] [PubMed] [Google Scholar]
  32. Purnelle B., Skala J., Van Dyck L., Goffeau A. The sequence of a 12 kb fragment on the left arm of yeast chromosome XI reveals five new open reading frames, including a zinc finger protein and a homolog of the UDP-glucose pyrophosphorylase from potato. Yeast. 1992 Nov;8(11):977–986. doi: 10.1002/yea.320081108. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Rose M., Albig W., Entian K. D. Glucose repression in Saccharomyces cerevisiae is directly associated with hexose phosphorylation by hexokinases PI and PII. Eur J Biochem. 1991 Aug 1;199(3):511–518. doi: 10.1111/j.1432-1033.1991.tb16149.x. [DOI] [PubMed] [Google Scholar]
  35. Rubin-Bejerano I., Mandel S., Robzyk K., Kassir Y. Induction of meiosis in Saccharomyces cerevisiae depends on conversion of the transcriptional represssor Ume6 to a positive regulator by its regulated association with the transcriptional activator Ime1. Mol Cell Biol. 1996 May;16(5):2518–2526. doi: 10.1128/mcb.16.5.2518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Schultz J., Carlson M. Molecular analysis of SSN6, a gene functionally related to the SNF1 protein kinase of Saccharomyces cerevisiae. Mol Cell Biol. 1987 Oct;7(10):3637–3645. doi: 10.1128/mcb.7.10.3637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Smith R. L., Redd M. J., Johnson A. D. The tetratricopeptide repeats of Ssn6 interact with the homeo domain of alpha 2. Genes Dev. 1995 Dec 1;9(23):2903–2910. doi: 10.1101/gad.9.23.2903. [DOI] [PubMed] [Google Scholar]
  38. Strich R., Surosky R. T., Steber C., Dubois E., Messenguy F., Esposito R. E. UME6 is a key regulator of nitrogen repression and meiotic development. Genes Dev. 1994 Apr 1;8(7):796–810. doi: 10.1101/gad.8.7.796. [DOI] [PubMed] [Google Scholar]
  39. Treitel M. A., Carlson M. Repression by SSN6-TUP1 is directed by MIG1, a repressor/activator protein. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3132–3136. doi: 10.1073/pnas.92.8.3132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Trumbly R. J. Glucose repression in the yeast Saccharomyces cerevisiae. Mol Microbiol. 1992 Jan;6(1):15–21. doi: 10.1111/j.1365-2958.1992.tb00832.x. [DOI] [PubMed] [Google Scholar]
  41. Tzamarias D., Struhl K. Distinct TPR motifs of Cyc8 are involved in recruiting the Cyc8-Tup1 corepressor complex to differentially regulated promoters. Genes Dev. 1995 Apr 1;9(7):821–831. doi: 10.1101/gad.9.7.821. [DOI] [PubMed] [Google Scholar]
  42. Tzamarias D., Struhl K. Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex. Nature. 1994 Jun 30;369(6483):758–761. doi: 10.1038/369758a0. [DOI] [PubMed] [Google Scholar]
  43. Vallier L. G., Coons D., Bisson L. F., Carlson M. Altered regulatory responses to glucose are associated with a glucose transport defect in grr1 mutants of Saccharomyces cerevisiae. Genetics. 1994 Apr;136(4):1279–1285. doi: 10.1093/genetics/136.4.1279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wendell D. L., Bisson L. F. Expression of high-affinity glucose transport protein Hxt2p of Saccharomyces cerevisiae is both repressed and induced by glucose and appears to be regulated posttranslationally. J Bacteriol. 1994 Jun;176(12):3730–3737. doi: 10.1128/jb.176.12.3730-3737.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Williams F. E., Varanasi U., Trumbly R. J. The CYC8 and TUP1 proteins involved in glucose repression in Saccharomyces cerevisiae are associated in a protein complex. Mol Cell Biol. 1991 Jun;11(6):3307–3316. doi: 10.1128/mcb.11.6.3307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. 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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