Analysis of gene network regulating yeast multidrug resistance by artificial activation of transcription factors: involvement of Pdr3 in salt tolerance

We established a strategy to constitutively activate Zn 2Cys 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,...

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Bibliographic Details
Published in:Gene 2004-05, Vol.332, p.51-59
Main Authors: Onda, Miyuki, Ota, Kazuhisa, Chiba, Tomoko, Sakaki, Yoshiyuki, Ito, Takashi
Format: Article
Language:English
Subjects:
ATP-Binding Cassette Transporters - genetics
Calcium - pharmacology
DNA microarray
DNA-Binding Proteins - genetics
Drug Resistance, Multiple, Fungal - genetics
Gene Expression Regulation, Fungal - drug effects
Mutation
Pdr1
Phylogeny
Pleiotropic drug resistance
Recombinant Fusion Proteins - genetics
Saccharomyces cerevisiae - drug effects
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - growth & development
Saccharomyces cerevisiae Proteins - genetics
Sodium - pharmacology
Sodium Chloride - pharmacology
Time Factors
Trans-Activators - genetics
Transcription Factors - genetics
Transcriptome
Transformation, Genetic
Yrr1
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Summary:We established a strategy to constitutively activate Zn 2Cys 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.
ISSN:0378-1119
1879-0038
DOI:10.1016/j.gene.2004.02.003