title: Analysis of gene network regulating yeast multidrug resistance by artificial activation of transcription factors: involvement of Pdr3 in salt tolerance.
abstract: We established a strategy to constitutively activate Zn(2)Cys(6)-type protein by fusing its DNA-binding domain with the VP16 trans-activation domain. To explore gene network regulating yeast multidrug resistance, the strategy was applied to Pdr1, Pdr3 and Yrr1, known to regulate multidrug resistance, as well as three uncharacterized Yrr1-related transcription factors. DNA microarray analysis revealed that all of the six mutants induce typical drug transporter genes including SNQ2 and YOR1, suggesting redundancy in regulation. On the other hand, each displays a unique spectrum of targets, which is coincident with the phylogenetic tree of the transcription factors and presumably reflects their functional specification. Indeed, careful analysis of target genes specific to each transcription factor led us to reveal an unexpected role for Pdr3 in salt tolerance. The strategy would thus contribute not only to identify target genes but to reveal redundancy and specificity in complex gene regulatory networks.
authors.affiliation: Division of Genome Biology, Cancer Research Institute, Kanazawa University, Kanazawa 920-0934, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Onda
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ota
authors.forename: Tomoko
authors.initials: T
authors.lastname: Chiba
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sakaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002118:Calcium / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D009154:Mutation; D010802:Phylogeny; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D012964:Sodium / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014170:Transformation, Genetic
chemical_list: D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; C085480:PDR1 protein, S cerevisiae; C089261:PDR3 protein, S cerevisiae; C092438:PDR5 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; C101797:SNQ2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C097077:YOR1 protein, S cerevisiae; C481276:Yrm1 protein, S cerevisiae; C481277:Yrr1 protein, S cerevisiae; D012965:Sodium Chloride; D012964:Sodium; D002118:Calcium