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Papers In Press, published online ahead of print January 14, 2003
J. Biol. Chem, 10.1074/jbc.M208549200
Submitted on August 21, 2002
Revised on January 14, 2003
Accepted on January 14, 2003

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

Imrich Hikkel, Ancuta Lucau-Danila, Thierry Delaveau, Philippe Marc, Frédéric Devaux, and Claude Jacq

Laboratoire de genetique moleculaire, Ecole Normale Superieure-CNRS, Paris 75005

Corresponding Author: jacq{at}biologie.ens.fr

We demonstrate a genome-wide 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 (Zn2Cys6) 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 (ChIP) 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 ABC or MFS transporters, like PDR15, YOR1 or AZR1 or for other proteins like SNG1, YJL216c, 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 anymous transcription factor is likely to be generalized to all the Zn2Cys6 transcription factors from S. cerevisiae and related yeasts.


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