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Cited by 204Fungal and yeast genetics researchIron Metabolism and DisordersPlant Micronutrient Interactions and Effects

Transcriptional Remodeling in Response to Iron Deprivation in Saccharomyces cerevisiae

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Shakoury-Elizeh, Minoo, Tiedeman, John, Rashford, Jared, Ferea, Tracey, Demeter, Janos, Garcia, Emily, Rolfes, Ronda, Brown, Patrick O. +2 more·2004·Molecular Biology of the Cell
DOI 10.1091/mbc.e03-09-0642PMC PMC363115
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Abstract

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.

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  • S. cerevisiae employs an iron regulatory system completely different from those employed by other fungi, with Aft1 as the major activator of iron uptake and recycling under iron restriction and Aft2 contributing redundantly.

    “S. cerevisiae employs an iron regulatory system completely different from those employed by other fungi. Here, Aft1 is the major activator of iron uptake and recycling under iron restriction conditions (21, 22), together with its paralog Aft2, which contributes in a largely redundant manner (23).”

    From A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts (2016) · cites this paper as [22]

  • In S. cerevisiae, the Aft1 regulon recruits the mRNA-degrading protein Cth2, which posttranscriptionally reduces the abundance of iron consumption-related mRNAs under conditions of iron deprivation.

    “In S. cerevisiae, the Aft1 regulon is known to recruit the mRNA-degrading protein Cth2 (also known as Tis11), which posttranscriptionally reduces the abundance of iron consumption-related mRNAs under conditions of iron deprivation (22, 24).”

    From A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts (2016) · cites this paper as [22]

  • S. cerevisiae Cth2, along with its paralog Cth1, targets mRNA of iron-dependent genes for degradation via binding to this motif.

    “S. cerevisiae Cth2 (ScCth2), along with its paralog Cth1, was found specifically to target mRNA of iron-dependent genes for degradation via binding to this motif (22, 24), whereas the corresponding Cth2 protein in C. glabrata was still uncharacterized.”

    From A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts (2016) · cites this paper as [22]

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Authors
Shakoury-Elizeh, M., Tiedeman, J., Rashford, J., Ferea, T., Demeter, J., Garcia, E., Rolfes, R., Brown, P. O., Botstein, D., & Philpott, C. C.
Affiliations
  • Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
  • National Institutes of Health (US)
  • Stanford University (US)
  • Department of Genetics, Stanford University, Stanford, California 94305
ORCID
Venue
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Published
2004-03
Volume
15
Issue
3
Pages
1233-1243
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
DOI
10.1091/mbc.e03-09-0642
PMC
PMC363115
OpenAlex
W2107451370
Cited by
204
References
58
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 4 · 2018: 9 · 2017: 11 · 2016: 10 · 2015: 4 · 2014: 6 · 2013: 17 · 2012: 14
FWCI
3.45
Type
journal article
Language
en
Open access
Locations
  • Molecular Biology of the Cell (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
Keywords
iron starvation, Saccharomyces cerevisiae, transcriptional remodeling, iron absorption, biotin biosynthesis, biotin synthase, glutamate synthase, nitrogen assimilation, purine biosynthesis, iron-sulfur clusters, transcriptional repression
MeSH terms
Base Sequence, Glutamate Synthase, Iron, Molecular Sequence Data, Nitrogen, Purines, Saccharomyces cerevisiae, Sulfurtransferases, Transcription Factors, Signal Transduction, Gene Expression Regulation, Fungal, Oligonucleotide Array Sequence Analysis, Saccharomyces cerevisiae Proteins

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