title: Oxygen-dependent transcriptional regulator Hap1p limits glucose uptake by repressing the expression of the major glucose transporter gene RAG1 in Kluyveromyces lactis.
abstract: The HAP1 (CYP1) gene product of Saccharomyces cerevisiae is known to regulate the transcription of many genes in response to oxygen availability. This response varies according to yeast species, probably reflecting the specific nature of their oxidative metabolism. It is suspected that a difference in the interaction of Hap1p with its target genes may explain some of the species-related variation in oxygen responses. As opposed to the fermentative S. cerevisiae, Kluyveromyces lactis is an aerobic yeast species which shows different oxygen responses. We examined the role of the HAP1-equivalent gene (KlHAP1) in K. lactis. KlHap1p showed a number of sequence features and some gene targets (such as KlCYC1) in common with its S. cerevisiae counterpart, and KlHAP1 was capable of complementing the hap1 mutation. However, the KlHAP1 disruptant showed temperature-sensitive growth on glucose, especially at low glucose concentrations. At normal temperature, 28 degrees C, the mutant grew well, the colony size being even greater than that of the wild type. The most striking observation was that KlHap1p repressed the expression of the major glucose transporter gene RAG1 and reduced the glucose uptake rate. This suggested an involvement of KlHap1p in the regulation of glycolytic flux through the glucose transport system. The DeltaKlhap1 mutant showed an increased ability to produce ethanol during aerobic growth, indicating a possible transformation of its physiological property to Crabtree positivity or partial Crabtree positivity. Dual roles of KlHap1p in activating respiration and repressing fermentation may be seen as a basis of the Crabtree-negative physiology of K. lactis.
authors.affiliation: Institut de Génétique et Microbiologie, CNRS UMR 8621, Bâtiment 400, Université Paris XI, 91405 Orsay, France.
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Bao
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.forename: Zi-An
authors.initials: ZA
authors.lastname: Fang
authors.forename: Claudia
authors.initials: C
authors.lastname: Donnini
authors.forename: Michel
authors.initials: M
authors.lastname: Gervais
authors.forename: Flavia M Lopes
authors.initials: FM
authors.lastname: Passos
authors.forename: Iliana
authors.initials: I
authors.lastname: Ferrero
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuhara
authors.forename: Monique
authors.initials: M
authors.lastname: Bolotin-Fukuhara
mesh_terms: D015536:Down-Regulation; D000431:Ethanol / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics* / Q000378:metabolism; D007716:Kluyveromyces / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D005656:Fungal Proteins; D051246:Glucose Transport Proteins, Facilitative; D014157:Transcription Factors; D000431:Ethanol; D010100:Oxygen