Structure of the transcriptional network controlling white‐opaque switching in C andida albicans
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Summary: The human fungal pathogen C andida albicans can switch between two phenotypic cell types, termed ‘white’ and ‘opaque’. Both cell types are heritable for many generations, and the switch between the two types occurs epigenetically, that is, without a change in the primary DNA sequence of the genome. Previous work identified six key transcriptional regulators important for white‐opaque switching: Wor1 , Wor2 , Wor3 , Czf1 , Efg1 , and Ahr1 . In this work, we describe the structure of the transcriptional network that specifies the white and opaque cell types and governs the ability to switch between them. In particular, we use a combination of genome‐wide chromatin immunoprecipitation, gene expression profiling, and microfluidics‐based DNA binding experiments to determine the direct and indirect regulatory interactions that form the switch network. The six regulators are arranged together in a complex, interlocking network with many seemingly redundant and overlapping connections. We propose that the structure (or topology) of this network is responsible for the epigenetic maintenance of the white and opaque states, the switching between them, and the specialized properties of each state.
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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 [32]
The Introduction states that Wor2 is required for heritable maintenance of the opaque cell type, supporting that part of the claim. The Results identify Wor2 as part of the switching circuit and indicate that deleting core regulators affects switching rates, but the copy does not establish that Wor2 is required for the white-to-opaque transition under regular culture conditions. (LLM, conf=0.84)
Experimental — accuracy not yet measuredWOR2 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 [32]
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The Wor2 phenotypic switching regulator controls biofilm formation in Candida auris
Liang, W., Guan, S., Bing, J., Du, H., Zheng, Q., Tao, L., Li, B., Huang, G., & Chu, H. (2026) · npj Biofilms and Microbiomes · doi:10.1038/s41522-026-01043-2
- Authors
- Hernday, A. D., Lohse, M. B., Fordyce, P. M., Nobile, C. J., DeRisi, J. L., & Johnson, A. D.
- Affiliations
- University of California, San Francisco (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Johnson, Alexander D.
- ORCID
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2013-08-25
- Volume
- 90
- Issue
- 1
- Pages
- 22-35
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- PMC
- PMC3888361
- OpenAlex
- W2168937034
- Cited by
- 131
- References
- 0
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 8 · 2023: 13 · 2022: 8 · 2021: 11 · 2020: 10 · 2019: 10 · 2018: 4 · 2017: 9 · 2016: 15 · 2015: 15 · 2014: 11 · 2013: 1
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI049187, F32AI071433, K99AI100896)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- Candida albicans, white-opaque switching, transcriptional regulatory networks, epigenetic switching, Wor1, EFG1, transcription factors, network topology, chromatin binding, fungal dimorphism
- MeSH terms
- Candida albicans, DNA, Fungal, Humans, Models, Biological, Phenotype, Protein Binding, Gene Expression Profiling, Microfluidics, Epigenesis, Genetic, Chromatin Immunoprecipitation, Gene Regulatory Networks
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