Mot3 is a transcriptional repressor of ergosterol biosynthetic genes and is required for normal vacuolar function in Saccharomyces cerevisiae
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The Saccharomyces cerevisiae MOT3 gene encodes a nuclear protein implicated in both repression and activation of transcription. However, a mot3 Delta mutation causes only mild phenotypes under normal growth conditions. To learn more about Mot3 function, we have performed a synthetic lethal screen. This screen identified PAN1, a gene required for normal endocytosis, and VPS41, a gene required for vacuolar fusion and protein targeting, suggesting a role for Mot3 in the regulation of membrane-related genes. Transcriptional analyses show that Mot3 represses transcription of ERG2, ERG6 and ERG9, genes required for ergosterol biosynthesis, during both aerobic and hypoxic growth. Chromatin immunoprecipitation experiments suggest that this repression is direct. Ergosterol has been shown to be required for endocytosis and homotypic vacuole fusion, providing a link between Mot3 and these processes. Consistent with these results, mot3 Delta mutants have a number of related defects, including impaired homotypic vacuole fusion and increased sterol levels. Taken together, our data suggest that proper transcriptional regulation of ergosterol biosynthetic genes by Mot3 is important for normal vacuolar function and probably for the endocytic membrane transport system.
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Mot3 represses the expression of hypoxic, DAN/TIR/PAU and ERG genes including ERG2, ERG6 and ERG9.
“In addition, to limit Ecm22 function [75], the transcriptional factor Mot3 also represses the expression of hypoxic, DAN/TIR/PAU and ERG genes including ERG2, ERG6 and ERG9 (Figure 3A) [86,89,90,91,92,93].”
From Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae (2020) · cites this paper as [92]
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- Authors
- Hongay, C., Jia, N., Bard, M., & Winston, F.
- Affiliations
- Harvard University (US)
- Indiana University – Purdue University Indianapolis (US)
- Corresponding author
- Winston, Fred
- ORCID
- Winston, Fred
- Venue
- The EMBO Journal
- Published
- 2002-08-01
- Volume
- 21
- Issue
- 15
- Pages
- 4114-4124
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC126159
- OpenAlex
- W2095617518
- Cited by
- 72
- References
- 69
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 6 · 2018: 2 · 2017: 5 · 2015: 2 · 2014: 1 · 2013: 7 · 2012: 1
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (1F31GM19933-03, R01GM062104, GM 62104, F31GM019933, R01GM045720, GM 45720)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- transcriptional repression, ergosterol biosynthesis, ERG2, ERG6, vacuole fusion, homotypic fusion, endocytosis, VPS41, sterol homeostasis, membrane transport, Saccharomyces cerevisiae
- MeSH terms
- Aerobiosis, Anaerobiosis, Carrier Proteins, DNA, Fungal, Endocytosis, Ergosterol, Fungal Proteins, Genes, Lethal, Methyltransferases, Microfilament Proteins, Nuclear Proteins, Promoter Regions, Genetic, Recombinant Fusion Proteins, Repressor Proteins, RNA, Fungal, RNA, Messenger, Saccharomyces cerevisiae, Steroid Isomerases, Transcription Factors, Vacuoles, Trans-Activators, Gene Expression Regulation, Fungal, RNA-Binding Proteins, Saccharomyces cerevisiae Proteins, Vesicular Transport Proteins
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