Transcriptional remodeling in response to iron deprivation in Saccharomyces cerevisiae.
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.
Shakoury-Elizeh
Minoo
M
Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Tiedeman
John
J
Rashford
Jared
J
Ferea
Tracey
T
Demeter
Janos
J
Garcia
Emily
E
Rolfes
Ronda
R
Brown
Patrick O
PO
Botstein
David
D
Philpott
Caroline C
CC
D001483:Base Sequence; D015966:Gene Expression Regulation, Fungal / Q000235:genetics / Q000502:physiology; D005970:Glutamate Synthase / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008969:Molecular Sequence Data; D009584:Nitrogen / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011687:Purines / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013466:Sulfurtransferases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
C090297:AFT1 protein, S cerevisiae; D011687:Purines; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D007501:Iron; D005970:Glutamate Synthase; D013466:Sulfurtransferases; C057985:biotin synthetase; D009584:Nitrogen; C030985:purine