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Originally published In Press as doi:10.1074/jbc.M011256200 on January 26, 2001

J. Biol. Chem., Vol. 276, Issue 18, 15472-15480, May 4, 2001
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The Fission Yeast Copper-sensing Transcription Factor Cuf1 Regulates the Copper Transporter Gene Expression through an Ace1/Amt1-like Recognition Sequence*

Jude Beaudoin and Simon LabbéDagger

From the Département de Biochimie, Université de Sherbrooke, Sherbrooke, Québec, J1H 5N4, Canada

Transcriptional regulation of genes encoding critical components of copper transport is essential for copper homeostasis and growth in yeast. Analysis of regulatory regions in the promoter of the ctr4+ copper transporter gene in fission yeast Schizosaccharomyces pombe reveals the identity of a conserved copper-signaling element (CuSE), which is recognized by the transcription factor Cuf1. We demonstrate that CuSE is necessary for transcriptional activation in response to copper deprivation conditions. Interestingly, the CuSE element bears a strong sequence similarity to the recognition site, denoted MRE (metal regulatory element), which is recognized by a distinct class of copper sensors required for copper detoxification, including Ace1 from Saccharomyces cerevisiae and Amt1 from Candida glabrata. When a consensus MRE from S. cerevisiae is introduced into S. pombe, transcription is induced by copper deprivation in a Cuf1-dependent manner, similar to regulation by Mac1, the nuclear sensor for regulating the expression of genes encoding components involved in copper transport in S. cerevisiae. UV-cross-linking experiments show that the Cuf1 protein directly binds the CuSE. These results demonstrate that the Cuf1 nutritional copper-sensing factor possesses a module that functions similarly to domains found in the Ace1/Amt1 class of metalloregulatory factors, which allows the protein to act through a closely related MRE-like sequence to regulate copper transport gene expression in S. pombe.

* This study was supported by Medical Research Council of Canada Grant MOP-42406 (to S. L.). Infrastructure equipment essential for conducting this investigation was obtained through Canada Foundation for Innovation Grant NOF-3754 (to S. L.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger A Fonds de la Recherche en Santé du Québec Scholar. To whom correspondence should be addressed: Tel.: 819-820-6868 (ext. 15460) or 819-564-5281; Fax: 819-564-5340; E-mail: slabbe@courrier.usherb.ca.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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