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J. Biol. Chem., Vol. 278, Issue 52, 52641-52650, December 26, 2003

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Competitive Promoter Occupancy by Two Yeast Paralogous Transcription Factors Controlling the Multidrug Resistance Phenomenon^*

Ancuta Lucau-Danila, Thierry Delaveau, Gaëlle Lelandais, Frédéric Devaux, and Claude Jacq

From the Laboratoire de Génétique Moléculaire, Ecole Normale Supérieure, 46 rue d'Ulm 75230 Paris cedex 05, France

Highly flexible gene expression programs are required to allow cell growth in the presence of a wide variety of chemicals. We used genome-wide expression analyses coupled with chromatin immunoprecipitation experiments to study the regulatory relationships between two very similar yeast transcription factors involved in the control of the multidrug resistance phenomenon. Yrm1 (Yor172w) is a new zinc finger transcription factor, the overproduction of which decreases the level of transcription of the target genes of Yrr1, a zinc finger transcription factor controlling the expression of several membrane transporter-encoding genes. Surprisingly, the absence of YRR1 releases the transcriptional activity of Yrm1, which then up-regulates 23 genes, 14 of which are also direct target genes of Yrr1. Chromatin immunoprecipitation experiments confirmed that Yrm1 binds to the promoters of the up-regulated genes only in yeast strains from which YRR1 has been deleted. This sophisticated regulatory program can be associated with drug resistance phenotypes of the cell. The program-specific distribution of paired transcription factors throughout the genome may be a general mechanism by which similar transcription factors regulate overlapping gene expression programs in response to chemical stress.

Received for publication, August 28, 2003 , and in revised form, September 24, 2003.

^* This work was supported in part by CNRS Grant Puces à ADN 2003 and a PRFMMIP grant from the Ministère de la Recherche et de la Technologie. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Supplementary Materials.

To whom correspondence should be addressed. Tel.: 33-1-44323546; E-mail: jacq{at}biologie.ens.fr; Web address: www.biologie.ens.fr/lgmgml.

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