Temporal anatomy of an epigenetic switch in cell programming: the white‐opaque transition of <i>C. albicans</i>

Lohse, Matthew B.; Johnson, Alexander D.

doi:10.1111/j.1365-2958.2010.07331.x

Cited by 38 publications

(40 citation statements)

References 42 publications

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“…To determine whether the signaling pathways leading to white-opaque switching were impacted in Mediator mutants, we measured opaque-white switching frequency at 37°C and white-opaque switching frequency in the presence of 5% CO 2 . Measuring switching frequency at 37°C affords the ability to monitor the kinetics of switching after the temperature of the liquid culture hosting the cells is raised from 25°C to 37°C (54). The med5⌬/⌬ mutant strain, which did not affect opaque-white switching frequency (Table 1) compared to the WT, exhibited kinetics of switching identical to those seen with the WT at 37°C (Fig.…”

Section: Resultsmentioning

confidence: 93%

Differential Regulation of White-Opaque Switching by Individual Subunits of Candida albicans Mediator

2013

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The multisubunit eukaryotic Mediator complex integrates diverse positive and negative gene regulatory signals and transmits them to the core transcription machinery. Mutations in individual subunits within the complex can lead to decreased or increased transcription of certain subsets of genes, which are highly specific to the mutated subunit. Recent studies suggest a role for Mediator in epigenetic silencing. Using white-opaque morphological switching in Candida albicans as a model, we have shown that Mediator is required for the stability of both the epigenetic silenced (white) and active (opaque) states of the bistable transcription circuit driven by the master regulator Wor1. Individual deletions of eight C. albicans Mediator subunits have shown that different Mediator subunits have dramatically diverse effects on the directionality, frequency, and environmental induction of epigenetic switching. Among the Mediator deletion mutants analyzed, only Med12 has a steady-state transcriptional effect on the components of the Wor1 circuit that clearly corresponds to its effect on switching. The MED16 and MED9 genes have been found to be among a small subset of genes that are required for the stability of both the white and opaque states. Deletion of the Med3 subunit completely destabilizes the opaque state, even though the Wor1 transcription circuit is intact and can be driven by ectopic expression of Wor1. The highly impaired ability of the med3 deletion mutant to mate, even when Wor1 expression is ectopically induced, reveals that the activation of the Wor1 circuit can be decoupled from the opaque state and one of its primary biological consequences.

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Section: Resultsmentioning

confidence: 93%

Differential Regulation of White-Opaque Switching by Individual Subunits of Candida albicans Mediator

2013

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“…It should be noted, however, that several characteristic features of C. albicans opaque cells are not seen in C. tropicalis, such as red staining with the chemical phloxine B (35) (Fig. S3) and switching of opaque cells en masse to white cells at 37°C (36,37) (Fig. 1F).…”

Section: Resultsmentioning

confidence: 98%

“…4A and Tables S4 and S5). Comparison with C. albicans white-opaque cell types (37,(40)(41)(42)(43) revealed that most phasespecific genes were species-specific. Thus, of the 134 opaquespecific genes in C. tropicalis that have homologs in C. albicans, only 25 (19%) were opaque-specific in both species.…”

Section: Resultsmentioning

confidence: 99%

“…Curiously, C. albicans Wor1 and H. capsulatum Ryp1 are associated with temperature-induced changes in cell fate. In the case of C. albicans, opaque cells are unstable at 37°C, because Wor1 expression is compromised and cells rapidly convert en masse to the white state (36,37). In contrast, C. tropicalis opaque cells are stable at 37°C, thereby allowing efficient mating at the body temperature of the mammalian host.…”

Section: Discussionmentioning

confidence: 99%

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Discovery of a phenotypic switch regulating sexual mating in the opportunistic fungal pathogen Candida tropicalis

Porman

Alby

Hirakawa

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

111

151

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Sexual reproduction can promote genetic diversity in eukaryotes, and yet many pathogenic fungi have been labeled as obligate asexual species. It is becoming increasingly clear, however, that cryptic sexual programs may exist in some species, and that efficient mating requires the necessary developmental switch to be triggered. In this study we investigate Candida tropicalis, an important human fungal pathogen that has been reported to be asexual. Significantly, we demonstrate that C. tropicalis uses a phenotypic switch to regulate a cryptic program of sexual mating. Thus, diploid a and α cells must undergo a developmental transition to the mating-competent form, and only then does efficient cell-cell conjugation take place resulting in the formation of stable a/α tetraploids. We show that both the phenotypic switch and sexual mating depend on the conserved transcriptional regulator Wor1, which is regulated by temperature in other fungal species. In contrast, C. tropicalis mating occurs efficiently at both 25°C and 37°C, suggesting that it could occur in the mammalian host and have direct consequences for the outcome of an infection. Transcriptional profiling further reveals that ≈400 genes are differentially expressed between the two phenotypic states, including the regulatory factor Wor1. Taken together, our results demonstrate that C. tropicalis has a unique sexual program, and that entry to this program is controlled via a Wor1-mediated, metastable switch. These observations have direct implications for the regulation and evolution of cryptic sexual programs in related fungal pathogens.epigenetic | recombination | bistability

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“…The role for signaling through the Ras/ cAMP/PKA pathway in virulence of C. albicans has been clearly established and thoroughly reviewed (51,52). Cutting-edge research on this fungal pathogen has revealed important new insights into the transcriptional regulatory networks that act in concert with Ras-regulated transcription factors to control cell adhesion (53), biofilm formation (54), morphogenesis (55), and W-O switching (56)(57)(58), processes in which Ras/cAMP/PKA signaling plays a central but not a sole role (Fig. 2).…”

Section: Ras/camp/pka Signaling Controls Known and Putative Pathogenimentioning

confidence: 99%

Ras Signaling Gets Fine-Tuned: Regulation of Multiple Pathogenic Traits of Candida albicans

Inglis

Sherlock

2013

Eukaryot Cell

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a Candida albicans is an opportunistic fungal pathogen that can cause disseminated infection in patients with indwelling catheters or other implanted medical devices. A common resident of the human microbiome, C. albicans responds to environmental signals, such as cell contact with catheter materials and exposure to serum or CO 2 , by triggering the expression of a variety of traits, some of which are known to contribute to its pathogenic lifestyle. Such traits include adhesion, biofilm formation, filamentation, white-to-opaque (W-O) switching, and two recently described phenotypes, finger and tentacle formation. Under distinct sets of environmental conditions and in specific cell types (mating type-like a [MTLa]/alpha cells, MTL homozygotes, or daughter cells), C. albicans utilizes (or reutilizes) a single signal transduction pathway-the Ras pathway-to affect these phenotypes. Ras1, Cyr1, Tpk2, and Pde2, the proteins of the Ras signaling pathway, are the only nontranscriptional regulatory proteins that are known to be essential for regulating all of these processes. How does C. albicans utilize this one pathway to regulate all of these phenotypes? The regulation of distinct and yet related processes by a single, evolutionarily conserved pathway is accomplished through the use of downstream transcription factors that are active under specific environmental conditions and in different cell types. In this minireview, we discuss the role of Ras signaling pathway components and Ras pathway-regulated transcription factors as well as the transcriptional regulatory networks that fine-tune gene expression in diverse biological contexts to generate specific phenotypes that impact the virulence of C. albicans.

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Temporal anatomy of an epigenetic switch in cell programming: the white‐opaque transition of C. albicans

Cited by 38 publications

References 42 publications

Differential Regulation of White-Opaque Switching by Individual Subunits of Candida albicans Mediator

Differential Regulation of White-Opaque Switching by Individual Subunits of Candida albicans Mediator

Discovery of a phenotypic switch regulating sexual mating in the opportunistic fungal pathogen Candida tropicalis

Ras Signaling Gets Fine-Tuned: Regulation of Multiple Pathogenic Traits of Candida albicans

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