Sterol regulatory element binding protein is a principal regulator of anaerobic gene expression in fission yeast.
Open accessAbstract
Fission yeast sterol regulatory element binding protein (SREBP), called Sre1p, functions in an oxygen-sensing pathway to allow adaptation to fluctuating oxygen concentrations. The Sre1p-Scp1p complex responds to oxygen-dependent sterol synthesis as an indirect measure of oxygen availability. To examine the role of Sre1p in anaerobic gene expression in Schizosaccharomyces pombe, we performed transcriptional profiling experiments after a shift to anaerobic conditions for 1.5 h. Of the 4,940 genes analyzed, expression levels of 521 (10.5%) and 686 (13.9%) genes were significantly increased and decreased, respectively, under anaerobic conditions. Sre1p controlled 68% of genes induced > or = 2-fold. Oxygen-requiring biosynthetic pathways for ergosterol, heme, sphingolipid, and ubiquinone were primary targets of Sre1p. Induction of glycolytic genes and repression of mitochondrial oxidative phosphorylation genes largely did not require Sre1p. Using chromatin immunoprecipitation, we demonstrated that Sre1p acts directly at target gene promoters and stimulates its own transcription under anaerobic conditions. sre1+ promoter analysis identified two DNA elements that are both necessary and sufficient for oxygen-dependent, Sre1p-dependent transcription. Interestingly, these elements are homologous to sterol regulatory elements bound by mammalian SREBP, highlighting the evolutionary conservation between Sre1p and SREBP. We conclude that Sre1p is a principal activator of anaerobic gene expression, upregulating genes required for nonrespiratory oxygen consumption.
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Sre1 is required for adaptation to hypoxia and regulated approximately 68% of the genes transcriptionally induced greater than 2-fold in response to anaerobic conditions.
“Sre1 was found to be required for adaptation to hypoxia and regulated approximately 68% of the genes transcriptionally induced greater than 2-fold in response to anaerobic conditions [31].”
From A Sterol-Regulatory Element Binding Protein Is Required for Cell Polarity, Hypoxia Adaptation, Azole Drug Resistance, and Virulence in Aspergillus fumigatus (2008) · cites this paper as [31]
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- Authors
- Todd, B. L., Stewart, E. V., Burg, J. S., Hughes, A. L., & Espenshade, P. J.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2006-04-01
- Volume
- 26
- Issue
- 7
- Pages
- 2817-2831
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC1430309
- OpenAlex
- W2104657811
- Cited by
- 172
- References
- 37
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 6 · 2018: 5 · 2017: 9 · 2016: 7 · 2015: 11 · 2014: 5 · 2013: 6 · 2012: 11
- FWCI
- 6.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL077588, HL 077588)
- National Institute of General Medical Sciences (GM007445, T32GM007445)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- SREBP, anaerobic gene expression, oxygen sensing, Schizosaccharomyces pombe, transcriptional regulation, sterol biosynthesis, ergosterol biosynthesis, heme biosynthesis, sphingolipid biosynthesis, ubiquinone biosynthesis, promoter elements
- MeSH terms
- Anaerobiosis, Genes, Fungal, Oxygen, Promoter Regions, Genetic, Schizosaccharomyces, Time Factors, Down-Regulation, Up-Regulation, Gene Expression Regulation, Fungal, Schizosaccharomyces pombe Proteins, Regulatory Elements, Transcriptional
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