ArticlePLoS genetics2014
Zinc finger transcription factors displaced SREBP proteins as the major Sterol regulators during Saccharomycotina evolution.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 70 citations in OpenAlex.
- The Origin and Early Evolution of Fungi: Challenges, Inferences, and Principles.Annual review of cell and developmental biology · 2026Review
- Enzyme-constrained genome-scale model of Yarrowia lipolytica predicts growth-phase specific metabolic engineering targets.Applied microbiology and biotechnology · 2026Article
- Targeted regulation of sterol biosynthesis genes according to perturbations in ergosterol biosynthesis in fungi.Journal of advanced research · 2025Article
- Article
- Pathogenic Fungal Sensing and Responses to Stressful Host Environments.Annual review of microbiology · 2025Review
- Sterol regulation in Komagataella phaffii: Identification of sterol regulatory element binding proteins and their activation pathway.The Journal of biological chemistry · 2025Article
- The Dual PathogenJournal of fungi (Basel, Switzerland) · 2025Review
- Novel cell factory for the production of 24-epi-ergosterol, an un-natural semi-synthetic precursor for the production of brassinolide in Yarrowia lipolytica.World journal of microbiology & biotechnology · 2025Article
- Article
- A receptor kinase senses sterol by coupling with elicitins in auxotrophicProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Identification of Potential New Genes Related to the SREBP Pathway inBiomolecules · 2024Article
- Crucial Involvement of Heme Biosynthesis in Vegetative Growth, Development, Stress Response, and Fungicide Sensitivity ofInternational journal of molecular sciences · 2024Article
- Recent Advances in Understanding the Human Fungal Pathogen Hypoxia Response in Disease Progression.Annual review of microbiology · 2023Review
- Rapid Gene Target Tracking for Enhancing β-Carotene Production Using Flow Cytometry-Based High-Throughput Screening in Yarrowia lipolytica.Applied and environmental microbiology · 2022Article
- Coordinated Regulation of Membrane Homeostasis and Drug Accumulation by Novel Kinase STK-17 in Response to Antifungal Azole Treatment.Microbiology spectrum · 2022Article
- Loss-of-FunctionmSphere · 2021Article
- The SREBP (Sterol Regulatory Element-Binding Protein) pathway: a regulatory bridge between carotenogenesis and sterol biosynthesis in the carotenogenic yeast Xanthophyllomyces dendrorhous.Biological research · 2021Review
- Regulation of Ergosterol Biosynthesis inGenes · 2020Review
- Article
- Condition-specific series of metabolic sub-networks and its application for gene set enrichment analysis.Bioinformatics (Oxford, England) · 2019Article
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In most eukaryotes, including the majority of fungi, expression of sterol biosynthesis genes is regulated by Sterol-Regulatory Element Binding Proteins (SREBPs), which are basic helix-loop-helix transcription activators. However, in yeasts such as Saccharomyces cerevisiae and Candida albicans sterol synthesis is instead regulated by Upc2, an unrelated transcription factor with a Gal4-type zinc finger. The SREBPs in S. cerevisiae (Hms1) and C. albicans (Cph2) have lost a domain, are not major regulators of sterol synthesis, and instead regulate filamentous growth. We report here that rewiring of the sterol regulon, with Upc2 taking over from SREBP, likely occurred in the common ancestor of all Saccharomycotina. Yarrowia lipolytica, a deep-branching species, is the only genome known to contain intact and full-length orthologs of both SREBP (Sre1) and Upc2. Deleting YlUPC2, but not YlSRE1, confers susceptibility to azole drugs. Sterol levels are significantly reduced in the YlUPC2 deletion. RNA-seq analysis shows that hypoxic regulation of sterol synthesis genes in Y. lipolytica is predominantly mediated by Upc2. However, YlSre1 still retains a role in hypoxic regulation; growth of Y. lipolytica in hypoxic conditions is reduced in a Ylupc2 deletion and is abolished in a Ylsre1/Ylupc2 double deletion, and YlSre1 regulates sterol gene expression during hypoxia adaptation. We show that YlSRE1, and to a lesser extent YlUPC2, are required for switching from yeast to filamentous growth in hypoxia. Sre1 appears to have an ancestral role in the regulation of filamentation, which became decoupled from its role in sterol gene regulation by the arrival of Upc2 in the Saccharomycotina.
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