Interlocking Transcriptional Feedback Loops Control White-Opaque Switching in Candida albicans
Open accessAbstract
The human pathogen Candida albicans can assume either of two distinct cell types, designated "white" and "opaque." Each cell type is maintained for many generations; switching between them is rare and stochastic, and occurs without any known changes in the nucleotide sequence of the genome. The two cell types differ dramatically in cell shape, colony appearance, mating competence, and virulence properties. In this work, we investigate the transcriptional circuitry that specifies the two cell types and controls the switching between them. First, we identify two new transcriptional regulators of white-opaque switching, Czf1 and white-opaque regulator 2 (Wor2). Analysis of a large set of double mutants and ectopic expression strains revealed genetic relationships between CZF1, WOR2, and two previously identified regulators of white-opaque switching, WOR1 and EFG1. Using chromatin immunoprecipitation, we show that Wor1 binds the intergenic regions upstream of the genes encoding three additional transcriptional regulators of white-opaque switching (CZF1, EFG1, and WOR2), and also occupies the promoters of numerous white- and opaque-enriched genes. Based on these interactions, we have placed these four genes in a circuit controlling white-opaque switching whose topology is a network of positive feedback loops, with the master regulator gene WOR1 occupying a central position. Our observations indicate that a key role of the interlocking feedback loop network is to stably maintain each epigenetic state through many cell divisions.
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WOR2 encodes a transcription factor required for white-opaque phenotypic switching in Candida albicans.
“It has been demonstrated that WOR2 encodes a transcription factor required for white-opaque phenotypic switching in C. albicans32,33.”
From The Wor2 phenotypic switching regulator controls biofilm formation in Candida auris (2026) · cites this paper as [33]
In C. albicans, Wor2 is required for white-to-opaque switching and maintenance of the opaque cell type under regular culture conditions.
“In C. albicans, Wor2 is required for white-to-opaque switching and maintenance of the opaque cell type under regular culture conditions32,33.”
From The Wor2 phenotypic switching regulator controls biofilm formation in Candida auris (2026) · cites this paper as [33]
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Research works printed but not linked: 32
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- Authors
- Zordan, R. E., Miller, M. G., Galgoczy, D. J., Tuch, B. B., & Johnson, A. D.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Johnson, Alexander D
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2007-09-18
- Volume
- 5
- Issue
- 10
- Pages
- e256
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC1976629
- OpenAlex
- W2059398061
- Cited by
- 292
- References
- 0
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 9 · 2023: 12 · 2022: 8 · 2021: 11 · 2020: 13 · 2019: 17 · 2018: 11 · 2017: 15 · 2016: 25 · 2015: 18 · 2014: 23 · 2013: 27 · 2012: 16
- FWCI
- 7.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Science Foundation
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI049187, R01 AI 49187)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- Candida albicans, white-opaque switching, transcriptional feedback loop, Wor1, EFG1, transcription factors, chromatin binding, stochastic switching, virulence
- MeSH terms
- Candida albicans, Cell Differentiation, Genes, Switch, Promoter Regions, Genetic, Transcription Factors, Transcription, Genetic, Gene Expression Regulation, Fungal, Feedback, Physiological, Epigenesis, Genetic
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