title: A role for sterol levels in oxygen sensing in Saccharomyces cerevisiae.
abstract: Upc2p and Ecm22p are a pair of transcription factors responsible for the basal and induced expression of genes encoding enzymes of ergosterol biosynthesis in yeast (ERG genes). Upc2p plays a second role as a regulator of hypoxically expressed genes. Both sterols and heme depend upon molecular oxygen for their synthesis, and thus the levels of both have the potential to act as indicators of the oxygen environment of cells. Hap1p is a heme-dependent transcription factor that both Upc2 and Ecm22p depend upon for basal level expression of ERG genes. However, induction of both ERG genes and the hypoxically expressed DAN/TIR genes by Upc2p and Ecm22p occurred in response to sterol depletion rather than to heme depletion. Indeed, upon sterol depletion, Upc2p no longer required Hap1p to activate ERG genes. Mot3p, a broadly acting repressor/activator protein, was previously shown to repress ERG gene expression, but the mechanism was unclear. We established that Mot3p bound directly to Ecm22p and repressed Ecm22p- but not Upc2p-mediated gene induction.
authors.affiliation: Department of Molecular and Cellular Biology, Division of Genetics, Genomics, and Development, University of California, Berkeley, California 94701-3202, USA.
authors.forename: Brandon S J
authors.initials: BS
authors.lastname: Davies
authors.forename: Jasper
authors.initials: J
authors.lastname: Rine
mesh_terms: D015687:Cell Hypoxia / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004875:Ergosterol / Q000096:biosynthesis; D006418:Heme / Q000031:analogs & derivatives / Q000502:physiology; D008954:Models, Biological; D009154:Mutation; D010100:Oxygen / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013251:Steroid Isomerases / Q000378:metabolism; D013261:Sterols / Q000096:biosynthesis / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; C465208:ECM22 protein, S cerevisiae; C058452:HAP1 protein, S cerevisiae; C112006:MOT3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; D015534:Trans-Activators; D014157:Transcription Factors; C113958:UPC2 protein, S cerevisiae; C027728:heme a; D006418:Heme; D013251:Steroid Isomerases; C022669:delta(8)-delta(7)-sterol isomerase; D010100:Oxygen; D004875:Ergosterol