Abstract
The yeast CIT1 (mitochondrial citrate synthase) gene is subject to glucose repression and is further repressed by glucose plus glutamate. Based on deletion analysis of a CIT1-lacZ gene fusion, DNA sequences between -548 and -273 are required for full expression of CIT1. The region of transcription initiation and the putative TATA element are located at -150 to -100 and -195 respectively. A restriction fragment containing DNA sequences between -457 and -211 conferred activation and glucose-glutamate regulation when placed in either orientation upstream of a USA-less heterologous yeast gene. Deletion of DNA sequences between -291 and -273 specifically eliminated derepression of CIT1, and destroyed one of two closely-spaced, potential binding sites for the HAP2,3,4 transcriptional activator protein. Tenbase-pair block substitutions in the region -367 to -348 reduced glucose-repressed expression. Thus, it appears that distinct DNA sequences upstream of CIT1 activate expression in glucose-repressed and derepressed cells. Possible mechanisms of regulation by glutamate plus glucose, are discussed.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Beevers H (1979) Annu Rev Plant Physiol 30:159–194
Carlson M (1987) J Bacteriol 169:4873–4877
Chen W, Struhl K (1988) Proc Natl Acad Sci USA 85:2691–2695
Douglas MG, Geller BL, Emr SD (1986) Proc Natl Acad Sci USA 81:3983–3987
Flechtner VR, Hanson RS (1969) Biochim Biophys Acta 184:252–262
Folch J-LAG, Antaramian A, Rodriguez L, Bravo A, Brunner A, Gonzalez A (1989) J Bacteriol 171:6776–6781
Forsburg S, Guarente L (1990) Annu Rev Cell Biol 5:153–180
Fraenkel DG (1982) Carbohydrate metabolism. In: Strathern JN, Jones EW, Broach JR (eds) The molecular biology of the yeast Saccharomyces cerevisiae — metabolism and gene expression. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York
Gangloff SP, Marguet D, Lauquin GJ-M (1990) Mol Cell Biol 10:3551–3561
Gray CT, Wimpenny JWT, Hughes DE, Mossman MR (1966) Biochim Biophys Acta 117:33–41
Guarente L (1983) Methods Enzymol 101:181–191
Guarente L (1987) Annu Rev Genet 21:425–452
Guarente L (1988) Cell 52:303–305
Guarente L (1992) Messenger RNA transcription and its control in Saccharomyces cerevisiae. In: Jones EW, Pringle JR, Broach JR (eds) The molecular and cellular biology of the yeast Saccharomyces (vol. 2, Gene expression). Cold Spring Harbor Laboratory, Cold Spring Harbor, New York
Guarente L (1993) Mechanism and regulation of transcriptional activation in eukaryotes: conserved features from yeasts to humans. In: McKnight SL, Yamamoto KR (eds) Transcriptional regulation. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York
Guarente L, Mason T (1983) Cell 32:1279–1286
Guarente L, Ptashne M (1981) Proc Natl Acad Sci USA 78:2199–2203
Guarente L, Lalonde B, Gifford P, Alani E (1984) Cell 36:503–511
Hahn S, Hoar ET, Guarente L (1985) Proc Natl Acad Sci USA 82:8562–8566
Hanson RS, MacKechnie I (1969) Regulation of sporulation and the entry of carbon into the tricarboxylic acid cycle. In: Campbell LL (ed) Spores IV. American Society for Microbiology, Washington, D.C.
Hinnebusch AG, Lucchini G, Fink GR (1985) Proc Natl Acad Sci USA 82:498–502
Hsu Y-P, Kohlhaw GB (1982) J Biol Chem 257:39–41
Joshi AK, Baichwal V, Ames GF-L (1991) Bio Techniques 10:42–45
Kim KS, Rosenkrantz MS, Guarente L (1986) Mol Cell Biol 6:1936–1942
Kispal G, Rosenkrantz M, Guarente L, Srere PA (1988) J Biol Chem 263:11145–11149
Kispal G, Evans CT, Malloy C, Srere PA (1989) J Biol Chem 264:11204–11210
Krebs HA, Lowenstein JM (1960) The tricarboxylic acid cycle. In: Greenberg DM (ed) Metabolic pathways. Academic Press, New York, New York
Lalo D, Stettler S, Mariotte S, Slonimski PP, Thuriaux P (1993) C R Acad Sci Paris 316:367–373
Lewin AS, Hines V, Small GM (1990) Mol Cell Biol 10:1399–1405
Liao X, Butow RA (1993) Cell 72:61–71
Liao X, Small WC, Srere PA, Butow RA (1991) Mol Cell Biol 11:38–46
Mattoon JR, Caravajal E, Guthrie D (1990) Curr Genet 17:179–183
McAlister-Henn L, Thompson LM (1987) J Bacteriol 169:5157–5166
McCammon MT, Veenhuis M, Trapp SB, Goodman JM (1990) J Bacteriol 172:5816–5827
McKnight SL, Kingsbury R (1982) Science 217:316–324
Nagawa F, Fink GR (1985) Proc Natl Acad Sci USA 82:8557–8561
Nimmo H (1987) The tricarboxylic acid cycle and anaplerotic reactions. In: Neidhardt F, Ingraham J, Low KB, Magasanik B, Schaechter M, Umbarger HE (eds) Escherichia coli and Salmonella typhimurium: cellular and molecular biology. American Society for Microbiology, Washington, D.C.
Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T (1989) Proc Natl Acad Sci USA 86:2766–2770
Parvin R (1969) Methods Enzymol 13:16–19
Pinkham J, Keng T (1993) Heme-mediated gene regulation in Saccharomyces cerevisiae. In: Winkelmann G, Winge DR (eds) Metal ions in fungi. Marcel Dekker, New York
Pon L, Schatz G (1991) Biogenesis of yeast mitochondria. In: Broach JR, Pringle JR, Jones EW (eds) The molecular biology of the yeast Saccharomyces. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York
Repetto B, Tzagoloff A (1989) Mol Cell Biol 9:2695–2705
Repetto B, Tzagoloff A (1990) Mol Cell Biol 10:4221–4232
Rickey TM, Lewin AS (1986) Mol Cell Biol 6:488–493
Rogers Yocum R, Hanley S, West R,Jr, Ptashne M (1984) Mol Cell Biol 4:1985–1998
Rosenkrantz MS, Dingman DW, Sonenshein AL (1985) J Bacteriol 164:155–164
Rosenkrantz MS, Alam T, Kim KS, Clark BJ, Srere PA, Guarente LP (1986) Mol Cell Biol 6:4509–4515
Roy DJ, Dawes IW (1987) J Gen Microbiol 133:925–933
Ruden DM, Ma J, Ptashne M, (1988) Proc Natl Acad Sci USA 85:4262–4266
Sanger F, Nicklen S, Coulson AR (1977) Proc Natl Acad Sci USA 74:5463–5467
Sarkar G, Sommer SS (1990) Bio Techniques 4:404–407
Schneider JC, Guarente L (1991) Mol Cell Biol 11:4934–4942
Sherman F, Fink GR, Hicks JB (1986) Methods in yeast genetics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York
Singh KK, Small GM, Lewin AS (1992) Mol Cell Biol 12:5593–5599
Srere PA (1969) Methods Enzymol 13:3–11
Suissa M, Suda K, Schatz G (1984) EMBO J 3:1773–1781
Trumbly RJ (1992) Mol Microbiol 6:15–21
Tzagoloff A, Myers AM (1986) Annu Rev Biochem 55:249–285
Verdier J-M (1990) Yeast 6:271–297
Walsh K, Koshland DE, Jr (1985) Proc Natl Acad Sci USA 82:3577–3581
Wilde RJ, Guest JR (1986) J Gen Microbiol 132:3239–3251
Wright RM, Poyton RO (1990) Mol Cell Biol 10:1297–1300
Yap EPH, McGee JO'D (1993) Trends Genet 8:49
Author information
Authors and Affiliations
Additional information
Communicated by L.A. Grivell
Rights and permissions
About this article
Cite this article
Rosenkrantz, M., Kell, C.S., Pennell, E.A. et al. Distinct upstream activation regions for glucose-repressed and derepressed expression of the yeast citrate synthase gene CIT1 . Curr Genet 25, 185–195 (1994). https://doi.org/10.1007/BF00357161
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00357161