title: Distinct upstream activation regions for glucose-repressed and derepressed expression of the yeast citrate synthase gene CIT1.
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 UAS-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. Ten-base-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.
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University/Medical College of Virginia, Richmond 23298-0678.
authors.forename: M
authors.initials: M
authors.lastname: Rosenkrantz
authors.forename: C S
authors.initials: CS
authors.lastname: Kell
authors.forename: E A
authors.initials: EA
authors.lastname: Pennell
authors.forename: M
authors.initials: M
authors.lastname: Webster
authors.forename: L J
authors.initials: LJ
authors.lastname: Devenish
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D023081:CCAAT-Binding Factor; D002950:Citrate (si)-Synthase / Q000096:biosynthesis / Q000235:genetics*; D002952:Citric Acid Cycle / Q000187:drug effects; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D023081:CCAAT-Binding Factor; D005656:Fungal Proteins; D007527:Isoenzymes; D007773:Lactates; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D019344:Lactic Acid; D018698:Glutamic Acid; D002950:Citrate (si)-Synthase; D005947:Glucose