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Originally published In Press as doi:10.1074/jbc.M206214200 on July 2, 2002

J. Biol. Chem., Vol. 277, Issue 37, 33749-33757, September 13, 2002
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Combinatorial Control of Yeast FET4 Gene Expression by Iron, Zinc, and Oxygen*

Brian M. WatersDagger and David J. Eide§

From the Departments of Dagger  Agronomy and § Nutritional Sciences, University of Missouri, Columbia, Missouri 65211

Acquisition of metals such as iron, copper, and zinc by the yeast Saccharomyces cerevisiae is tightly regulated. High affinity uptake systems are induced under metal-limiting conditions to maintain an adequate supply of these essential nutrients. Low affinity uptake systems function when their substrates are in greater supply. The FET4 gene encodes a low affinity iron and copper uptake transporter. FET4 expression is regulated by several environmental factors. In this report, we describe the molecular mechanisms underlying this regulation. First, we found that FET4 expression is induced in iron-limited cells by the Aft1 iron-responsive transcriptional activator. Second, FET4 is regulated by zinc status via the Zap1 transcription factor. We present evidence that FET4 is a physiologically relevant zinc transporter and this provides a rationale for its regulation by Zap1. Finally, FET4 expression is regulated in response to oxygen by the Rox1 repressor. Rox1 attenuates activation by Aft1 and Zap1 in aerobic cells. Derepression of FET4 may allow the Fet4 transporter to play an even greater role in metal acquisition under anaerobic conditions. Thus, Fet4 is a multisubstrate metal ion transporter under combinatorial control by iron, zinc, and oxygen.

* This work was supported by National Institutes of Health Grant GM56285 and the University of Missouri Plant Sciences Unit.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.

To whom correspondence should be addressed: Dept. of Nutritional Sciences, 217 Gwynn Hall, University of Missouri, Columbia, MO 65211. Tel.: 573-882-9686; Fax: 573-882-0185; E-mail: eided@missouri.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


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