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Mol Cell Biol. Jun 1994; 14(6): 3834–3841.
PMCID: PMC358750

Multiple mechanisms provide rapid and stringent glucose repression of GAL gene expression in Saccharomyces cerevisiae.

Abstract

Expression of the GAL genes of Saccharomyces cerevisiae is induced during growth on galactose by a well-characterized regulatory mechanism that relieves Gal80p inhibition of the Gal4p transcriptional activator. Growth on glucose overrides induction by galactose. Glucose repression acts at three levels to reduce GAL1 expression: (i) it reduces the level of functional inducer in the cell; (ii) it lowers cellular levels of Gal4p by repressing GAL4 transcription; and (iii) it inhibits Gal4p function through a repression element in the GAL1 promoter. We quantified the amount of repression provided by each mechanism by assaying strains with none, one, two, or all three of the repression mechanisms intact. In a strain lacking all three repression mechanisms, there was almost no glucose repression of GAL1 expression, suggesting that these are the major, possibly the only, mechanisms of glucose repression acting upon the GAL genes. The mechanism of repression that acts to reduce Gal4p levels in the cell is established slowly (hours after glucose addition), probably because Gal4p is stable. By contrast, the repression acting through the upstream repression sequence element in the GAL1 promoter is established rapidly (within minutes of glucose addition). Thus, these three mechanisms of repression collaborate to repress GAL1 expression rapidly and stringently. The Mig1p repressor is responsible for most (possibly all) of these repression mechanisms. We show that for GAL1 expression, mig1 mutations are epistatic to snf1 mutations, indicating that Mig1p acts after the Snf1p protein kinase in the glucose repression pathway, which suggests that Snf1p is an inhibitor of Mig1p.

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Selected References

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  • Adams BG. Induction of galactokinase in Saccharomyces cerevisiae: kinetics of induction and glucose effects. J Bacteriol. 1972 Aug;111(2):308–315. [PMC free article] [PubMed]
  • Bajwa W, Torchia TE, Hopper JE. Yeast regulatory gene GAL3: carbon regulation; UASGal elements in common with GAL1, GAL2, GAL7, GAL10, GAL80, and MEL1; encoded protein strikingly similar to yeast and Escherichia coli galactokinases. Mol Cell Biol. 1988 Aug;8(8):3439–3447. [PMC free article] [PubMed]
  • Bhat PJ, Hopper JE. Overproduction of the GAL1 or GAL3 protein causes galactose-independent activation of the GAL4 protein: evidence for a new model of induction for the yeast GAL/MEL regulon. Mol Cell Biol. 1992 Jun;12(6):2701–2707. [PMC free article] [PubMed]
  • Bram RJ, Lue NF, Kornberg RD. A GAL family of upstream activating sequences in yeast: roles in both induction and repression of transcription. EMBO J. 1986 Mar;5(3):603–608. [PMC free article] [PubMed]
  • Celenza JL, Carlson M. A yeast gene that is essential for release from glucose repression encodes a protein kinase. Science. 1986 Sep 12;233(4769):1175–1180. [PubMed]
  • Elder RT, Loh EY, Davis RW. RNA from the yeast transposable element Ty1 has both ends in the direct repeats, a structure similar to retrovirus RNA. Proc Natl Acad Sci U S A. 1983 May;80(9):2432–2436. [PMC free article] [PubMed]
  • Erickson JR, Johnston M. Genetic and molecular characterization of GAL83: its interaction and similarities with other genes involved in glucose repression in Saccharomyces cerevisiae. Genetics. 1993 Nov;135(3):655–664. [PMC free article] [PubMed]
  • Finley RL, Jr, Chen S, Ma J, Byrne P, West RW., Jr Opposing regulatory functions of positive and negative elements in UASG control transcription of the yeast GAL genes. Mol Cell Biol. 1990 Nov;10(11):5663–5670. [PMC free article] [PubMed]
  • Flick JS, Johnston M. Two systems of glucose repression of the GAL1 promoter in Saccharomyces cerevisiae. Mol Cell Biol. 1990 Sep;10(9):4757–4769. [PMC free article] [PubMed]
  • Flick JS, Johnston M. Analysis of URSG-mediated glucose repression of the GAL1 promoter of Saccharomyces cerevisiae. Genetics. 1992 Feb;130(2):295–304. [PMC free article] [PubMed]
  • Giniger E, Ptashne M. Cooperative DNA binding of the yeast transcriptional activator GAL4. Proc Natl Acad Sci U S A. 1988 Jan;85(2):382–386. [PMC free article] [PubMed]
  • Griggs DW, Johnston M. Regulated expression of the GAL4 activator gene in yeast provides a sensitive genetic switch for glucose repression. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8597–8601. [PMC free article] [PubMed]
  • Herrick D, Parker R, Jacobson A. Identification and comparison of stable and unstable mRNAs in Saccharomyces cerevisiae. Mol Cell Biol. 1990 May;10(5):2269–2284. [PMC free article] [PubMed]
  • Johnston M, Davis RW. Sequences that regulate the divergent GAL1-GAL10 promoter in Saccharomyces cerevisiae. Mol Cell Biol. 1984 Aug;4(8):1440–1448. [PMC free article] [PubMed]
  • Johnston M. A model fungal gene regulatory mechanism: the GAL genes of Saccharomyces cerevisiae. Microbiol Rev. 1987 Dec;51(4):458–476. [PMC free article] [PubMed]
  • Shah HC, Carlson GP. Alteration by phenobarbital and 3-methyl-cholanthrene of functional and structural changes in rat liver due to carbon tetrachloride inhalation. J Pharmacol Exp Ther. 1975 Apr;193(1):281–292. [PubMed]
  • Johnston SA, Salmeron JM, Jr, Dincher SS. Interaction of positive and negative regulatory proteins in the galactose regulon of yeast. Cell. 1987 Jul 3;50(1):143–146. [PubMed]
  • Keegan L, Gill G, Ptashne M. Separation of DNA binding from the transcription-activating function of a eukaryotic regulatory protein. Science. 1986 Feb 14;231(4739):699–704. [PubMed]
  • Lamphier MS, Ptashne M. Multiple mechanisms mediate glucose repression of the yeast GAL1 gene. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5922–5926. [PMC free article] [PubMed]
  • Ma J, Ptashne M. The carboxy-terminal 30 amino acids of GAL4 are recognized by GAL80. Cell. 1987 Jul 3;50(1):137–142. [PubMed]
  • Matern H, Holzer H. Catabolite inactivation of the galactose uptake system in yeast. J Biol Chem. 1977 Sep 25;252(18):6399–6402. [PubMed]
  • Mylin LM, Bhat JP, Hopper JE. Regulated phosphorylation and dephosphorylation of GAL4, a transcriptional activator. Genes Dev. 1989 Aug;3(8):1157–1165. [PubMed]
  • Nehlin JO, Carlberg M, Ronne H. Control of yeast GAL genes by MIG1 repressor: a transcriptional cascade in the glucose response. EMBO J. 1991 Nov;10(11):3373–3377. [PMC free article] [PubMed]
  • Nehlin JO, Carlberg M, Ronne H. Yeast SKO1 gene encodes a bZIP protein that binds to the CRE motif and acts as a repressor of transcription. Nucleic Acids Res. 1992 Oct 25;20(20):5271–5278. [PMC free article] [PubMed]
  • Nehlin JO, Ronne H. Yeast MIG1 repressor is related to the mammalian early growth response and Wilms' tumour finger proteins. EMBO J. 1990 Sep;9(9):2891–2898. [PMC free article] [PubMed]
  • Neigeborn L, Carlson M. Genes affecting the regulation of SUC2 gene expression by glucose repression in Saccharomyces cerevisiae. Genetics. 1984 Dec;108(4):845–858. [PMC free article] [PubMed]
  • Parthun MR, Jaehning JA. A transcriptionally active form of GAL4 is phosphorylated and associated with GAL80. Mol Cell Biol. 1992 Nov;12(11):4981–4987. [PMC free article] [PubMed]
  • Ramos J, Cirillo VP. Role of cyclic-AMP-dependent protein kinase in catabolite inactivation of the glucose and galactose transporters in Saccharomyces cerevisiae. J Bacteriol. 1989 Jun;171(6):3545–3548. [PMC free article] [PubMed]
  • Sadowski I, Niedbala D, Wood K, Ptashne M. GAL4 is phosphorylated as a consequence of transcriptional activation. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10510–10514. [PMC free article] [PubMed]
  • Schüller HJ, Entian KD. Isolation and expression analysis of two yeast regulatory genes involved in the derepression of glucose-repressible enzymes. Mol Gen Genet. 1987 Sep;209(2):366–373. [PubMed]
  • Schüller HJ, Entian KD. Extragenic suppressors of yeast glucose derepression mutants leading to constitutive synthesis of several glucose-repressible enzymes. J Bacteriol. 1991 Mar;173(6):2045–2052. [PMC free article] [PubMed]
  • Selleck SB, Majors JE. In vivo DNA-binding properties of a yeast transcription activator protein. Mol Cell Biol. 1987 Sep;7(9):3260–3267. [PMC free article] [PubMed]
  • Sikorski RS, 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. [PMC free article] [PubMed]
  • St John TP, Davis RW. The organization and transcription of the galactose gene cluster of Saccharomyces. J Mol Biol. 1981 Oct 25;152(2):285–315. [PubMed]
  • Stone G, Sadowski I. GAL4 is regulated by a glucose-responsive functional domain. EMBO J. 1993 Apr;12(4):1375–1385. [PMC free article] [PubMed]
  • Tschopp JF, Emr SD, Field C, Schekman R. GAL2 codes for a membrane-bound subunit of the galactose permease in Saccharomyces cerevisiae. J Bacteriol. 1986 Apr;166(1):313–318. [PMC free article] [PubMed]
  • Yocum RR, 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. [PMC free article] [PubMed]

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