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Proc Natl Acad Sci U S A. Oct 10, 1995; 92(21): 9722–9726.
PMCID: PMC40874

Regulation of yeast phospholipid biosynthetic gene expression in response to inositol involves two superimposed mechanisms.

Abstract

Transcription of phospholipid biosynthetic genes in the yeast Saccharomyces cerevisiae is maximally derepressed when cells are grown in the absence of inositol and repressed when the cells are grown in its presence. We have previously suggested that this response to inositol may be dictated by regulating transcription of the cognate activator gene, INO2. However, it was also known that cells which harbor a mutant opi1 allele express constitutively derepressed levels of target genes (INO1 and CHO1), implicating the OPI1 negative regulatory gene in the response to inositol. These observations suggested that the response to inositol may involve both regulation of INO2 transcription as well as OPI1-mediated repression. We investigated these possibilities by examining the effect of inositol on target gene expression in a strain containing the INO2 gene under control of the GAL1 promoter. In this strain, transcription of the INO2 gene was regulated in response to galactose but was insensitive to inositol. The expression of the INO1 and CHO1 target genes was still responsive to inositol even though expression of the INO2 gene was unresponsive. However, the level of expression of the INO1 and CHO1 target genes correlated with the level of INO2 transcription. Furthermore, the effect of inositol on target gene expression was eliminated by deleting the OPI1 gene in the GAL1-INO2-containing strain. These data suggest that the OPI1 gene product is the primary target (sensor) of the inositol response and that derepression of INO2 transcription determines the degree of expression of the target genes.

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Selected References

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  • Guarente L. Regulatory proteins in yeast. Annu Rev Genet. 1987;21:425–452. [PubMed]
  • Struhl K. Molecular mechanisms of transcriptional regulation in yeast. Annu Rev Biochem. 1989;58:1051–1077. [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]
  • Hinnebusch AG. Mechanisms of gene regulation in the general control of amino acid biosynthesis in Saccharomyces cerevisiae. Microbiol Rev. 1988 Jun;52(2):248–273. [PMC free article] [PubMed]
  • Herskowitz I. A regulatory hierarchy for cell specialization in yeast. Nature. 1989 Dec 14;342(6251):749–757. [PubMed]
  • Guarente L. UASs and enhancers: common mechanism of transcriptional activation in yeast and mammals. Cell. 1988 Feb 12;52(3):303–305. [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]
  • Hinnebusch AG. Novel mechanisms of translational control in Saccharomyces cerevisiae. Trends Genet. 1988 Jun;4(6):169–174. [PubMed]
  • Kornitzer D, Raboy B, Kulka RG, Fink GR. Regulated degradation of the transcription factor Gcn4. EMBO J. 1994 Dec 15;13(24):6021–6030. [PMC free article] [PubMed]
  • Nasmyth K, Adolf G, Lydall D, Seddon A. The identification of a second cell cycle control on the HO promoter in yeast: cell cycle regulation of SW15 nuclear entry. Cell. 1990 Aug 24;62(4):631–647. [PubMed]
  • Dohrmann PR, Butler G, Tamai K, Dorland S, Greene JR, Thiele DJ, Stillman DJ. Parallel pathways of gene regulation: homologous regulators SWI5 and ACE2 differentially control transcription of HO and chitinase. Genes Dev. 1992 Jan;6(1):93–104. [PubMed]
  • Leuther KK, Johnston SA. Nondissociation of GAL4 and GAL80 in vivo after galactose induction. Science. 1992 May 29;256(5061):1333–1335. [PubMed]
  • Jayaraman PS, Hirst K, Goding CR. The activation domain of a basic helix-loop-helix protein is masked by repressor interaction with domains distinct from that required for transcription regulation. EMBO J. 1994 May 1;13(9):2192–2199. [PMC free article] [PubMed]
  • Nikoloff DM, Henry SA. Genetic analysis of yeast phospholipid biosynthesis. Annu Rev Genet. 1991;25:559–583. [PubMed]
  • Lopes JM, Hirsch JP, Chorgo PA, Schulze KL, Henry SA. Analysis of sequences in the INO1 promoter that are involved in its regulation by phospholipid precursors. Nucleic Acids Res. 1991 Apr 11;19(7):1687–1693. [PMC free article] [PubMed]
  • Bailis AM, Lopes JM, Kohlwein SD, Henry SA. Cis and trans regulatory elements required for regulation of the CHO1 gene of Saccharomyces cerevisiae. Nucleic Acids Res. 1992 Mar 25;20(6):1411–1418. [PMC free article] [PubMed]
  • Blackwell TK, Weintraub H. Differences and similarities in DNA-binding preferences of MyoD and E2A protein complexes revealed by binding site selection. Science. 1990 Nov 23;250(4984):1104–1110. [PubMed]
  • Blackwell TK, Huang J, Ma A, Kretzner L, Alt FW, Eisenman RN, Weintraub H. Binding of myc proteins to canonical and noncanonical DNA sequences. Mol Cell Biol. 1993 Sep;13(9):5216–5224. [PMC free article] [PubMed]
  • Nikoloff DM, Henry SA. Functional characterization of the INO2 gene of Saccharomyces cerevisiae. A positive regulator of phospholipid biosynthesis. J Biol Chem. 1994 Mar 11;269(10):7402–7411. [PubMed]
  • Ambroziak J, Henry SA. INO2 and INO4 gene products, positive regulators of phospholipid biosynthesis in Saccharomyces cerevisiae, form a complex that binds to the INO1 promoter. J Biol Chem. 1994 May 27;269(21):15344–15349. [PubMed]
  • Schwank S, Ebbert R, Rautenstrauss K, Schweizer E, Schüller HJ. Yeast transcriptional activator INO2 interacts as an Ino2p/Ino4p basic helix-loop-helix heteromeric complex with the inositol/choline-responsive element necessary for expression of phospholipid biosynthetic genes in Saccharomyces cerevisiae. Nucleic Acids Res. 1995 Jan 25;23(2):230–237. [PMC free article] [PubMed]
  • Ashburner BP, Lopes JM. Autoregulated expression of the yeast INO2 and INO4 helix-loop-helix activator genes effects cooperative regulation on their target genes. Mol Cell Biol. 1995 Mar;15(3):1709–1715. [PMC free article] [PubMed]
  • White MJ, Hirsch JP, Henry SA. The OPI1 gene of Saccharomyces cerevisiae, a negative regulator of phospholipid biosynthesis, encodes a protein containing polyglutamine tracts and a leucine zipper. J Biol Chem. 1991 Jan 15;266(2):863–872. [PubMed]
  • Hirsch JP, Henry SA. Expression of the Saccharomyces cerevisiae inositol-1-phosphate synthase (INO1) gene is regulated by factors that affect phospholipid synthesis. Mol Cell Biol. 1986 Oct;6(10):3320–3328. [PMC free article] [PubMed]
  • Griggs DW, Johnston M. Promoter elements determining weak expression of the GAL4 regulatory gene of Saccharomyces cerevisiae. Mol Cell Biol. 1993 Aug;13(8):4999–5009. [PMC free article] [PubMed]
  • Elion EA, Warner JR. The major promoter element of rRNA transcription in yeast lies 2 kb upstream. Cell. 1984 Dec;39(3 Pt 2):663–673. [PubMed]
  • Bailis AM, Poole MA, Carman GM, Henry SA. The membrane-associated enzyme phosphatidylserine synthase is regulated at the level of mRNA abundance. Mol Cell Biol. 1987 Jan;7(1):167–176. [PMC free article] [PubMed]
  • Aparicio OM, Gottschling DE. Overcoming telomeric silencing: a trans-activator competes to establish gene expression in a cell cycle-dependent way. Genes Dev. 1994 May 15;8(10):1133–1146. [PubMed]
  • Shimada H, Fukasawa T. Controlled transcription of the yeast regulatory gene GAL80. Gene. 1985;39(1):1–9. [PubMed]
  • Nogi Y, Shimada H, Matsuzaki Y, Hashimoto H, Fukasawa T. Regulation of expression of the galactose gene cluster in Saccharomyces cerevisiae. II. The isolation and dosage effect of the regulatory gene GAL80. Mol Gen Genet. 1984;195(1-2):29–34. [PubMed]
  • Lopes JM, Henry SA. Interaction of trans and cis regulatory elements in the INO1 promoter of Saccharomyces cerevisiae. Nucleic Acids Res. 1991 Jul 25;19(14):3987–3994. [PMC free article] [PubMed]

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