A Role for Sterol Levels in Oxygen Sensing in Saccharomyces cerevisiae
Abstract
Upc2p and Ecm22p are a pair of transcription factors responsible for the basal and induced expression of genes encoding enzymes of ergosterol biosynthesis in yeast (ERG genes). Upc2p plays a second role as a regulator of hypoxically expressed genes. Both sterols and heme depend upon molecular oxygen for their synthesis, and thus the levels of both have the potential to act as indicators of the oxygen environment of cells. Hap1p is a heme-dependent transcription factor that both Upc2 and Ecm22p depend upon for basal level expression of ERG genes. However, induction of both ERG genes and the hypoxically expressed DAN/TIR genes by Upc2p and Ecm22p occurred in response to sterol depletion rather than to heme depletion. Indeed, upon sterol depletion, Upc2p no longer required Hap1p to activate ERG genes. Mot3p, a broadly acting repressor/activator protein, was previously shown to repress ERG gene expression, but the mechanism was unclear. We established that Mot3p bound directly to Ecm22p and repressed Ecm22p- but not Upc2p-mediated gene induction.
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Gain-of-function mutations in the activation domain located near the C terminus have been recovered from both ScUpc2 and ScEcm22; mediation of ERG11 expression during hypoxic conditions or when chemically treated with azole antifungals is mediated by ScUpc2.
“Gain-of-function mutations in the activation domain located near the C terminus have been recovered from both ScUpc2 and ScEcm22; however, mediation of ERG11 expression during hypoxic conditions or when chemically treated with azole antifungals is mediated by ScUpc2 (5).”
From Gain-of-Function Mutations in <i>UPC2</i> Are a Frequent Cause of <i>ERG11</i> Upregulation in Azole-Resistant Clinical Isolates of Candida albicans (2012) · cites this paper as [5]
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Experimental — accuracy not yet measuredThe expression of these genes is affected by sterol depletion.
“The expression of these genes is affected by sterol depletion, but the exact mechanism of activation is currently unknown.”
From Gain-of-Function Mutations in <i>UPC2</i> Are a Frequent Cause of <i>ERG11</i> Upregulation in Azole-Resistant Clinical Isolates of Candida albicans (2012) · cites this paper as [5]
The heme-dependent transcription factor Hap1 is also necessary for the expression of genes involved in ergosterol biosynthesis.
“The heme-dependent transcription factor Hap1 is also necessary for the expression of genes involved in ergosterol biosynthesis (Figure 3A) [75,79,80,81,82].”
From Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae (2020) · cites this paper as [75]
Conflicting results have been observed for the effect of Hap1 on the expression of ERG genes during anaerobic conditions.
“However, conflicting results have been observed for the effect of Hap1 on the expression of ERG genes during anaerobic conditions [75,96,99,100].”
From Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae (2020) · cites this paper as [75]
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References 49 · Cited by 123
Research works printed but not linked: 1
- -A simplified model of hypoxic induction of gene expression. Burke, D., D. Dawson and T. Stearns, 2000 Methods in Yeast Genet- ics. Cold Spring Harbor Laboratory Press, Woodbury, NY
- Authors
- Davies, B. S. J., & Rine, J.
- Affiliations
- University of California, Los Angeles (US)
- University of California, Berkeley (US)
- Corresponding author
- Rine, Jasper
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-09-01
- Volume
- 174
- Issue
- 1
- Pages
- 191-201
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- OpenAlex
- W2156679838
- Cited by
- 123
- References
- 49
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 8 · 2023: 2 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 10 · 2016: 2 · 2015: 6 · 2014: 7 · 2013: 7 · 2012: 14
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM035827, GM 35827)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- oxygen sensing, ergosterol biosynthesis, ERG gene, sterol depletion, heme, hypoxia, transcriptional regulation, Saccharomyces cerevisiae
- MeSH terms
- DNA-Binding Proteins, Ergosterol, Heme, Models, Biological, Mutation, Oxygen, Promoter Regions, Genetic, Protein Binding, Saccharomyces cerevisiae, Steroid Isomerases, Sterols, Transcription Factors, Transcriptional Activation, Trans-Activators, Cell Hypoxia, Saccharomyces cerevisiae Proteins
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