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A general strategy to uncover transcription factor properties identifies a new regulator of drug resistance in yeast.

TitleA general strategy to uncover transcription factor properties identifies a new regulator of drug resistance in yeast.
Publication TypeJournal Article
Year of Publication2003
AuthorsHikkel, I, Lucau-Danila, A, Delaveau, T, Marc, P, Devaux, F, Jacq, C
JournalJ Biol Chem
Volume278
Issue13
Pagination11427-32
Date Published2003 Mar 28
ISSN0021-9258
KeywordsDrug Resistance, Microbial, Genome, Fungal, Oligonucleotide Array Sequence Analysis, Phenotype, Precipitin Tests, Saccharomyces cerevisiae, Transcription Factors
Abstract

We demonstrate a genomewide approach to determine the physiological role of a putative transcription factor, Ylr266, identified through yeast genome sequencing program. We constructed activated forms of the zinc finger (Zn(2)Cys(6)) protein Ylr266, and we analyzed the corresponding transcriptomes with DNA microarrays to characterize the up-regulated genes. The direct target genes of Ylr266 were further identified by in vivo chromatin immunoprecipitation procedure. The functions of the genes directly controlled by YLR266c are in agreement with the observed drug-resistance phenotype of the cell expressing an activated form of Ylr266. These target genes code for ATP-binding cassette or major facilitator superfamily transporters such as PDR15, YOR1, or AZR1 or for other proteins such as SNG1, YJL216c, or YLL056c which are already known to be involved in the yeast pleiotropic drug resistance (PDR) phenomenon. YLR266c could thus be named PDR8. Overlaps with the other PDR networks argue in favor of a new specific role for PDR8 in connection with the well known PDR regulators PDR1/PDR3 and YRR1. This strategy to identify the regulatory properties of an anonymous transcription factor is likely to be generalized to all the Zn(2)Cys(6) transcription factors from Saccharomyces cerevisiae and related yeasts.

DOI10.1074/jbc.M208549200
Alternate JournalJ. Biol. Chem.
PubMed ID12529331

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