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J. Biol. Chem., Vol. 279, Issue 6, 4450-4458, February 6, 2004

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Exploratory and Confirmatory Gene Expression Profiling of mac1^*

Jeane Maria De Freitas, Jeung Hyoun Kim, Helen Poynton, Trent Su, Henri Wintz, Tama Fox, Patty Holman, Alex Loguinov, Sunduz Keles¶, Mark van der Laan¶, and Chris Vulpe||

From the Department of Nutritional Sciences and Toxicology and the ^¶Division of Biostatistics, University of California, Berkeley, California 94720

Exploratory outlier identification methods and confirmatory gene expression studies showed induction of the iron regulon in Saccharomyces cerevisiae lacking Mac1p, a copper-responsive transcription factor. The Aft1p/Aft2p binding motif was the most discriminating motif between up- and down-regulated genes, and we identified new genes potentially regulated by Aft1p/Aft2p. In addition, multiple genes encoding proteins containing Fe-S clusters were down-regulated suggesting metabolic reorganization to conserve iron in mac1. Null mutants of each of the differentially expressed genes were characterized for copper- or iron-related phenotypes. New or additional support for a role in copper and iron homeostasis is provided in this study for the gene products of AKR1, MRS4, PCA1, SSU1, TIS11, YBR047W, YHL035C, YHR045W, YLR047C, YLR126C, and YTP1.

Received for publication, December 3, 2002 , and in revised form, July 29, 2003.

^* This work was supported by grants from the International Copper Association and the University of California Life Sciences Informatics Program (to C. V.). 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 supplemental data.

Both authors contributed equally to this work.

^|| To whom correspondence should be addressed. Tel.: 510-642-1834; Fax: 510-642-0535; E-mail: vulpe{at}uclink4.berkeley.edu.

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