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A more recent version of this article appeared on March 1, 2004
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Submitted on September 4, 2003
Revised on October 15, 2003
Accepted on October 20, 2003
1 Liver Diseases Section, NIDDK, NIH
2 Liver Diseases Section, NIDDK, NIH, University of Virginia School of Medicine, Charlottesville VA
3 Liver Diseases Section, NIDDK, NIH, Roswell High School, Roswell GA
4 Department of Genetics, Stanford University, Stanford, CA; Applied Biosystems, Foster City, CA
5 Department of Genetics, Stanford University, Stanford, CA
6 Department of Biology, Georgetown University, Washington, DC; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA
7 Department of Biology, Georgetown University, Washington, DC
8 Department of Biochemistry, Stanford University, Stanford, CA
9 Institute for Integrative Genomics, Princeton University, Princeton, NJ
10 Liver Diseases Section, NIDDK, NIH, Building 10, Room 9B-16, 10 Center Drive, MSC 1800, Bethesda, MD 20892-1800
* Corresponding author. E-mail address: carolinep{at}intra.niddk.nih.gov.
The budding yeast S. 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, while 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.
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