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Expression of yeast cytochrome C1 is controlled at the transcriptional level by glucose, oxygen and haem

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Summary

The nuclear gene for cytochrome c 1 in Saccharomyces cerevisiae (CYT1) was localized on chromosome XV. Its upstream region was identified by functional complementation. Fusion to the lacZ reporter gene on a CEN plasmid allowed study of the effect of carbon sources and of specific deletion mutations on expression of the gene in yeast transformants. Detailed promoter analysis combined with expression studies in recipient strains defective in regulatory genes identified cis-acting sites and transcription factors involved in the regulated expression of the cytochrome c 1 gene. These analyses showed that, in the presence of glucose, transcription of CYT1 is positively controlled by oxygen, presumably through the haem signal, and mediated by the HAP1-encoded transactivator. It is additionally regulated by the HAP2/3/4 complex which mediates gene activation mainly under glucose-free conditions. Basal transcription is, in part, effected by CPF1, a centromere and promoter-binding factor.

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References

  • Attardi G, Schatz G (1988) Biogenesis of mitochondria. Annu Rev Cell Biol 4:289–333

    Google Scholar 

  • Bandlow W, Strobel G, Zoglowek C, Oechsner U, Magdolen V (1988) Yeast adenylate kinase is active simultaneously in mitochondria and cytoplasm and is required for non-fermentative growth. Eur J Biochem 178:451–457

    Google Scholar 

  • Bram RJ, Kornberg RD (1985) Specific protein binding to far upstream activating sequences in polymerase II promoters. Proc Natl Acad Sci USA 82:43–47

    Google Scholar 

  • Bram RJ, Kornberg RD (1987) Isolation of a Saccharomyces cerevisiae centromere DNA-binding protein, its human homolog, and its possible role as a transcription factor. Mol Cell Biol 7:403–409

    Google Scholar 

  • Cai M, Davis RW (1990) Yeast centromere binding protein CBF1, of the helix-loop-helix protein family, is required for chromosome stability and methionine prototrophy. Cell 61: 437–446

    Google Scholar 

  • Casadaban MJ, Martinez-Arias A, Shapira SK, Chou J (1983) β-Galactosidase gene fusion for analyzing gene expression in Escherichia coli and yeast. Methods Enzymol 100:293–308

    Google Scholar 

  • Chen E, Seeburg P (1985) Supercoil sequencing: A fast and simple method for sequencing plasmid DNA. DNA 4:165–170

    Google Scholar 

  • Creusot F, Verdière J, Gaisne M, Slonimski PP (1988) CYP1 (HAP1) regulator of oxygen-dependent gene expression in yeast: I. Overall organization of the protein sequence displays several novel structural domains. J Mol Biol 204:263–276

    Google Scholar 

  • Daum G, Böhni PC, Schatz G (1982) Import of proteins into mitochondria: Cytochrome b 2 and cytochrome c peroxidase are located in the intermembrane space of yeast mitochondria. J Biol Chem 257:13028–13033

    Google Scholar 

  • Dobson MJ, Tuite MF, Roberts NA, Kingsman AJ, Kingsman SM (1982) Conservation of high efficiency promoter sequences in Saccharomyces cerevisiae. Nucleic Acids Res 10:2625–2637

    Google Scholar 

  • Dorsman JC, van Heeswijk WC, Grivell LA (1988) 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 16:7287–7301

    Google Scholar 

  • Fitzgerald-Hayes M, Clarke L, Carbon J (1982) Nucleotide sequence comparisons and functional analysis of yeast centromere DNAs. Cell 29:235–244

    Google Scholar 

  • Forsburg SL, Guarente L (1988) Mutational analysis of upstream activation sequence 2 of the CYC1 gene of Saccharomyces cerevisiae: A HAP2-HAP3 responsive site. Mol Cell Biol 8:647–654

    Google Scholar 

  • Forsburg SL, Guarente L (1989) Communication between mitochondria and the nucleus in regulation of cytochrome genes in the yeast Saccharomyces cerevisiae. Annu Rev Cell Biol 5:153–180

    Google Scholar 

  • Grivell LA (1989) Nucleo-mitochondrial interactions in yeast mitochondrial biogenesis. Eur J Biochem 182:477–493

    Google Scholar 

  • Guarente L (1983) Yeast promoters and lacZ fusions designed to study expression of cloned genes in yeast. Methods Enzymol 101:181–191

    Google Scholar 

  • Guarente L (1988) UASs and enhancers: Common mechanism of transcriptional activation in yeast and mammals. Cell 52:303–305

    Google Scholar 

  • Guarente L, Mason T (1983) Heme regulates transcription of the CYC1 gene of S. cerevisiae via an upstream activation site. Cell 32:1279–1286

    Google Scholar 

  • Guarente L, Lalonde B, Gifford P, Alani E (1984) Distinctly regulated tandem upstream activation sites mediate catabolite repression of the CYC1 gene of S. cerevisiae. Cell 35:503–511

    Google Scholar 

  • Hieter P, Pridmore D, Hegemann JH, Thomas M, Davis RW, Philippsen P (1985) Functional selection and analysis of yeast centromeric DNA. Cell 42:913–921

    Google Scholar 

  • Hodge MR, Kim G, Singh K, Cumsky MG (1989) Inverse regulation of the yeast COX5 genes by oxygen and heme. Mol Cell Biol 9:1958–1964

    Google Scholar 

  • Keng T, Guarente L (1987) Constitutive expression of the yeast HEM1 gene is actually a composite of activation and repression. Proc Natl Acad Sci USA 84:9113–9117

    Google Scholar 

  • Kim KS, Pfeifer K, Powell L, Guarente L (1990) Internal deletions in the yeast transcriptional activator HAP1 have opposite effects at two sequence elements. Proc Natl Acad Sci USA 87:4524–4528

    Google Scholar 

  • Koerner TJ, Hill J, Tzagoloff A (1985) Cloning and characterization of the yeast nuclear gene for subunit 5 of cytochrome oxidase. J Biol Chem 260:9513–9515

    Google Scholar 

  • Labbe-Bois R, Urban-Grimal D, Volland C, Camadro JM, Dehoux P (1983) About the regulation of protoheme synthesis in the yeast Saccharomyces cerevisiae. In: Schweyen RJ, Wolf K, Kaudewitz F (eds) Mitochondria 1983. de Gruyter, Berlin, pp 523–534

    Google Scholar 

  • Lodi T, Guiard B (1991) Complex transcriptional regulation of the Saccharomyces cerevisiae CYB2 gene encoding cytochrome b 2: CYP1(HAP1) activator binds to the CYB2 upstream activation site UASI-B2. Mol Cell Biol 11: 3762–3772

    Google Scholar 

  • Lowry CV, Zitomer RS (1988) ROX1 encodes a heme-induced factor regulating ANB1 and CYC7 of Saccharomyces cerevisiae. Mol Cell Biol 8:4651–4658

    Google Scholar 

  • Lowry CV, Weiss JL, Walthall DA, Zitomer RS (1983) Modulator sequences mediate oxygen regulation of CYC1 and a neighboring gene in yeast. Proc Natl Acad Sci USA 80:151–155

    Google Scholar 

  • Lue NF, Buchman AR, Kornberg RD (1989) Activation of yeast RNA polymerase II transcription by a thymidine-rich upstream element in vivo. Proc Natl Acad Sci USA 86:468–490

    Google Scholar 

  • Ma H, Kunes S, Schatz JP, Botstein D (1987) Plasmid construction by homologous recombination in yeast. Gene 58:201–216

    Google Scholar 

  • Maarse AC, de Haan M, Bout A, Grivell LA (1988) Demarcation of a sequence involved in mediating catabolite repression of the gene for the 11 kDa subunit VIII of ubiquinol cytochrome c oxidoreductase in Saccharomyces cerevisiae. Nucleic Acids Res 16:5797–5811

    Google Scholar 

  • Magdolen V, Oechsner U, Müller G, Bandlow W (1988) The introncontaining gene for yeast profilin (PFY) encodes a vital function. Mol Cell Biol 8:5108–5115

    Google Scholar 

  • Magdolen V, Oechsner U, Trommler P, Bandlow W (1990) Transcriptional control by galactose of a yeast gene encoding a protein homologous to mammalian aldo/keto reductases. Gene 90:105–114

    Google Scholar 

  • Mason T, Little HN, van Sickle C, Guarente L (1983) The role of heme and oxygen in the regulation of mitochondrial cytochromes. In: Schweyen RJ, Wolf K, Kaudewitz F (eds) Mitochondria 1983. de Gruyter, Berlin, pp 509–522

    Google Scholar 

  • McKnight GL, McConaughy BL (1983) Selection of functional cDNAs by complementation in yeast. Proc Natl Acad Sci USA 80:4412–4416

    Google Scholar 

  • Mellor J, Jiang W, Funk M, Rathjen J, Barnes CA, Hinz T, Hegemann JH, Philippsen P (1990) CPF1, a yeast protein which functions in centromeres and promoters. EMBO J 9:4017–4026

    Google Scholar 

  • Mellor J, Rathjen J, Jiang W, Dowell SJ (1991) DNA binding of CPF1 is required for optimal centromere function but not for maintaining methionine prototrophy in yeast. Nucleic Acids Res 19:2961–2969

    Google Scholar 

  • Michaelis G, Mannhaupt G, Pratje E, Fisher E, Naggert J, Schweizer E (1982) In: Slonimski PP, Borst P, Attardi G (eds) Mitochondrial genes. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp 311–321

    Google Scholar 

  • Myers AM, Crivellone MD, Koerner TJ, Tzagoloff A (1987) Characterization of the yeast hem2 gene and transcriptional regulation of COX5 and COR1 by heme. J Biol Chem 262:16822–16829

    Google Scholar 

  • Ohashi A, Gibson J, Gregor I, Schatz G (1982) Import of proteins into mitochondria. The precursor of cytochrome cmax is processed in two steps, one of them heme-dependent. J Biol Chem 257:13042–13047

    Google Scholar 

  • Olesen JT, Guarente L (1990) The HAP2 subunit of yeast CCAAT transcriptional activator contains adjacent domains for subunit association and DNA recognition: model for the HAP2/3/4/ complex. Genes Dev 4:1714–1729

    Google Scholar 

  • Olesen J, Hahn S, Guarente L (1987) Yeast HAP2 and HAP3 activators both bind to the CYC1 upstream activation site, UAS2, in an interdependent manner. Cell 51:953–961

    Google Scholar 

  • Perlman PS, Mahler HR (1974) Derepression of mitochondria and their enzymes in yeast: regulatory aspects. Arch Biochem Biophys 162:248–271

    Google Scholar 

  • Pfeifer K, Arcangioli B, Guarente L (1987a) Yeast HAPI activator competes with the factor RC2 for binding to the upstream activation site UASI of the CYC1 gene. Cell 49:9–18

    Google Scholar 

  • Pfeifer K, Prezant T, Guarente L (1987b) Yeast HAPI activator binds to the upstream activation sites of different sequence. Cell 49:19–27

    Google Scholar 

  • Pfeifer K, Kim KS, Kogan S, Guarente L (1989) Functional dissection and sequence of yeast HAPI activator. Cell 56:291–301

    Google Scholar 

  • Pinkham JL, Olesen JT, Guarente LT (1987) Sequence and nuclear localization of the Saccharomyces cerevisiae HAP2 protein; a transcriptional activator. Mol Cell Biol 7:578–585

    Google Scholar 

  • Proudfoot N (1991) Poly(A) signals. Cell 64:671–674

    Google Scholar 

  • Ross E, Schatz G (1976) Cytochrome c 1 of baker's yeast. II. Synthesis on cytoplasmic ribosomes and the influence of oxygen and heme on accumulation of the apoprotein. J Biol Chem 251:1997–2004

    Google Scholar 

  • Rothstein RJ (1983) One-step gene disruption in yeast. Methods Enzymol 101:202–211

    Google Scholar 

  • Sadler I, Suda K, Schatz G, Kaudewitz F, Haid A (1984) Sequencing of the nuclear gene for the yeast cytochrome cmax precursor reveals an unusually complex amino-terminal presequence. EMBO J 3:2137–2143

    Google Scholar 

  • Sambrook J, Fritsch EF, Maniatis T, (1989) Molecular cloning: A laboratory manual, 2nd edn. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY

    Google Scholar 

  • Sherman F, Fink GR, Hicks JB (1986) Methods in yeast genetics: A laboratory manual, Revised edn. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp 1–196

    Google Scholar 

  • Strobel G, Magdolen V, Oechsner U, Huh HS, Bandlow W, (1988) The 5′-upstream region of the yeast 25S rRNA gene contains a promoter element allowing expression in yeast and E. coli. Curr Genet 14:293–302

    Google Scholar 

  • Suissa M, Suda K, Schatz G (1984) Isolation of the nuclear yeast genes for citrate synthase and fifteen other mitochondrial proteins by a new screening method. EMBO J 3:1773–1781

    Google Scholar 

  • Thomas D, Cherest H, Surdin-Kerjan Y (1989) Elements involved in S-adenosyhnethionine-mediated regulation of the Saccharomyces cerevisiae MET25 gene. Mol Cell Biol 9:3292–3298

    Google Scholar 

  • Trawick JD, Rogness C, Poyton RO (1989) Identification of an upstream activation sequence and other cis-acting elements required for transcription of COX6 from Saccharomyces cerevisiae. Mol Cell Biol 9:5350–5358

    Google Scholar 

  • Trumpower BL (1990) Cytochrome bc 1 complexes in microorganisms. Microbiol Rev 54:101–129

    Google Scholar 

  • van Loon APGM, de Groot RJ, van Eyk E, van der Horst KTJ, Grivell LA (1982) Isolation and characterization of the nuclear genes coding for subunits of the yeast ubiginol-cytochrome c reductase complex. Gene 20:323–337

    Google Scholar 

  • Verdière J, Gaisne M, Guiard B, Defranoux N, Slonimski PP (1988) CYPI (HAPI) regulator of oxygen-dependent gene expression in yeast: II. Missense mutations suggest alternative Zn-fingers as discriminating agents of gene control. J Mol Biol 204:277–282

    Google Scholar 

  • Winkler H, Adam G, Mattes E, Schatz M, Hartig A, Ruis H (1988) Co-ordinate control of synthesis of mitochondrial and nonmitochondrial hemoproteins: A binding site for the HAPI (CYP1) protein in the UAS region of the yeast catalase T gene (CTT1). EMBO J 7:1799–1804

    Google Scholar 

  • Winter E, Varshavsky A (1989) A DNA binding protein that recognizes oligo (dA) · (dT) tracts. EMBO J 8:1867–1877

    Google Scholar 

  • Woods RA, Sanders HK, Briquet M, Foury F, Drysdale BE, Mattoon JR (1975) Regulation of mitochondrial biogenesis: Enzymatic changes in cytochrome-deficient yeast mutants requiring σ-aminolevulinic acid. J Biol Chem 250:9090–9098

    Google Scholar 

  • Wright RM, Rosenzweig B, Poyton RO (1989) Organization and expression of the COX6 genetic locus in Saccharomyces cerevisiae. Multiple mRNAs with different 3′ termini are transcribed from COX6 and regulated differentially. Nucleic Acids Res 17:1103–1120

    Google Scholar 

  • Yanisch-Perron C, Vieira J, Messing J (1985) Improved M13 cloning vectors and host strains: nucleotide sequence of the M13mp18 and pUC19 vectors. Gene 33:103–119

    Google Scholar 

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Communicated by C.P. Hollenberg

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Oechsner, U., Hermann, H., Zollner, A. et al. Expression of yeast cytochrome C1 is controlled at the transcriptional level by glucose, oxygen and haem. Molec. Gen. Genet. 232, 447–459 (1992). https://doi.org/10.1007/BF00266250

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