<i>Candida albicans</i>Zcf37, a zinc finger protein, is required for stabilization of the white state

Wang, Huafeng; Song, Wei; Huang, Guanghua; Zhou, Zhou; Ding, Yufeng; Chen, Jiangye

doi:10.1016/j.febslet.2011.02.005

Cited by 39 publications

(41 citation statements)

References 30 publications

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“…In addition, the EFG1 gene is absent from C. tropicalis, and expression levels of a related APSES transcription factor, EFH1 (44), were similar between white and opaque forms. In C. albicans, the Mcm1-Ahr1 complex also regulates the white-opaque switch, yet the motif recognized by this complex is absent from other Candida species including C. tropicalis (27,45,46). Taken together, these findings establish that the transcriptional circuitry regulating the phenotypic switch in C. tropicalis is fundamentally distinct from that regulating the white-opaque switch in C. albicans.…”

Section: −6mentioning

confidence: 53%

“…For example, whiteopaque switching in C. albicans is regulated by the Mcm1-Ahr1 complex, yet the motif recognized by this complex is absent from species other than C. albicans/C. dubliniensis (22,46,47). In addition, the Efg1 transcription factor that is essential for formation of white cells in C. albicans, and is conserved in most hemiascomycete yeast, has been lost from the C. tropicalis genome (10).…”

Section: Discussionmentioning

confidence: 99%

“…Differences in the transcriptional regulation of the switch may account, at least in part, for the differential stability of the opaque states in C. albicans and C. tropicalis. Deletion of Ahr1 (also called Zcf37) in C. albicans increased the temperature stability of opaque cells (46), and it is therefore possible that the loss of this regulatory factor in C. tropicalis contributes to the increased thermal stability of the opaque state in this species.…”

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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Section: −6mentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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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“…Previous work has identified five key transcriptional regulators-Wor1, Wor2, Czf1, Efg1, and Ahr1-that control whiteopaque switching in C. albicans through a series of nested positive-feedback loops (21)(22)(23)(24) (Fig. 1).…”

mentioning

confidence: 99%

Identification and characterization of a previously undescribed family of sequence-specific DNA-binding domains

Lohse¹,

Hernday²,

Fordyce

et al. 2013

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

131

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Sequence-specific DNA-binding proteins are among the most important classes of gene regulatory proteins, controlling changes in transcription that underlie many aspects of biology. In this work, we identify a transcriptional regulator from the human fungal pathogen Candida albicans that binds DNA specifically but has no detectable homology with any previously described DNA-or RNA-binding protein. This protein, named White-Opaque Regulator 3 (Wor3), regulates white-opaque switching, the ability of C. albicans to switch between two heritable cell types. We demonstrate that ectopic overexpression of WOR3 results in mass conversion of white cells to opaque cells and that deletion of WOR3 affects the stability of opaque cells at physiological temperatures. Genome-wide chromatin immunoprecipitation of Wor3 and gene expression profiling of a wor3 deletion mutant strain indicate that Wor3 is highly integrated into the previously described circuit regulating white-opaque switching and that it controls a subset of the opaque transcriptional program. We show by biochemical, genetic, and microfluidic experiments that Wor3 binds directly to DNA in a sequence-specific manner, and we identify the set of cis-regulatory sequences recognized by Wor3. Bioinformatic analyses indicate that the Wor3 family arose more recently in evolutionary time than most previously described DNA-binding domains; it is restricted to a small number of fungi that include the major fungal pathogens of humans. These observations show that new families of sequence-specific DNA-binding proteins may be restricted to small clades and suggest that current annotations-which rely on deep conservation-underestimate the fraction of genes coding for transcriptional regulators.transcriptional regulation | transcription factor | transcription networks | epigenetic switch

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“…In the case of the white-opaque switch, a network of at least six transcription factors (AHR1, CZF1, EFG1, WOR1, WOR2 and WOR3) controls expression of 748 target genes [30, [75][76][77][78]. A detailed analysis of this circuit included ChIP-chip, global transcriptome analysis and mechanically induced trapping of molecular interactions (MITOMI) [75].…”

Section: Investigation Of Chromatin Structure and Transcriptional Regmentioning

confidence: 99%

Budding off: bringing functional genomics toCandida albicans

Anderson¹,

Bennett²

2015

Briefings in Functional Genomics

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Candida species are the most prevalent human fungal pathogens, with Candida albicans being the most clinically relevant species. Candida albicans resides as a commensal of the human gastrointestinal tract but is a frequent cause of opportunistic mucosal and systemic infections. Investigation of C. albicans virulence has traditionally relied on candidate gene approaches, but recent advances in functional genomics have now facilitated global, unbiased studies of gene function. Such studies include comparative genomics (both between and within Candida species), analysis of total RNA expression, and regulation and delineation of protein-DNA interactions. Additionally, large collections of mutant strains have begun to aid systematic screening of clinically relevant phenotypes. Here, we will highlight the development of functional genomics in C. albicans and discuss the use of these approaches to addressing both commensalism and pathogenesis in this species.

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Candida albicansZcf37, a zinc finger protein, is required for stabilization of the white state

Cited by 39 publications

References 30 publications

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

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

Identification and characterization of a previously undescribed family of sequence-specific DNA-binding domains

Budding off: bringing functional genomics toCandida albicans

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