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Vol. 15, Issue 3, 1233-1243, March 2004
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* Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892;
Department of Genetics, Stanford University, Stanford, California 94305
Submitted September 4, 2003;
Revised October 15, 2003;
Accepted October 20, 2003
Monitoring Editor: Trisha Davis
The budding yeast Saccharomyces cerevisiae responds to depletion of iron in the environment by activating Aft1p, the major iron-dependent transcription factor, and by transcribing systems involved in the uptake of iron. Here, we have studied the transcriptional response to iron deprivation and have identified new Aft1p target genes. We find that other metabolic pathways are regulated by iron: biotin uptake and biosynthesis, nitrogen assimilation, and purine biosynthesis. Two enzymes active in these pathways, biotin synthase and glutamate synthase, require an iron-sulfur cluster for activity. Iron deprivation activates transcription of the biotin importer and simultaneously represses transcription of the entire biotin biosynthetic pathway. Multiple genes involved in nitrogen assimilation and amino acid metabolism are induced by iron deprivation, whereas glutamate synthase, a key enzyme in nitrogen assimilation, is repressed. A CGG palindrome within the promoter of glutamate synthase confers iron-regulated expression, suggesting control by a transcription factor of the binuclear zinc cluster family. We provide evidence that yeast subjected to iron deprivation undergo a transcriptional remodeling, resulting in a shift from iron-dependent to parallel, but iron-independent, metabolic pathways.
Online version of this article contains supplementary material for some figures. Online version available at www.molbiolcell.org.
Present address: University of Virginia School of Medicine, Charlottesville, VA
Present address: Roswell High School, Roswell, GA
Present address: Department of Genetics, Stanford University, Stanford, CA
|| Present address: Applied Biosystems, Foster City, CA
¶ Present address: Department of Biology, Georgetown University, Washington, DC
# Present address: Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA
** Present address: Department of Biochemistry, Stanford University, Stanford, CA
Present address: Institute for Integrative Genomics, Princeton University, Princeton, NJ
Corresponding author. E-mail address: carolinep{at}intra.niddk.nih.gov.
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