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A conserved transcriptional regulator governs fungal morphology in widely diverged species [expression data]

ABSTRACT: In this paper, we examine orthologs of a transcriptional regulator in three fungal species, Saccharomyces cerevisiae, Candida albicans, and Histoplasma capsulatum. We show that, despite an estimated 600 million years since those species diverged from a common ancestor, Wor1 in C. albicans, Ryp1 in H. capsulatum, and Mit1 in S. cerevisiae recognize the same DNA motif. Previous work established that Wor1 regulates white-opaque switching in C. albicans and that its ortholog Ryp1 regulates the yeast to mycelial transition in H. capsulatum. Here we show that the ortholog Mit1 in S. cerevisiae also regulates a morphological transition, in this case pseudohyphal growth. Full genome chromatin immunoprecipitation experiments show that Mit1 binds to the control regions of approximately 94 genes including the previously known regulators of pseudohyphal growth. Through a comparison of full genome chromatin immunoprecipitation experiments for Mit1 in S. cerevisiae, Wor1 in C. albicans, and Wor1 ectopically expressed in S. cerevisiae, we conclude that genes controlled by the orthologous regulators overlap only slightly between these two species. We suggest that the ancestral Wor1/Mit1/Ryp1 protein controlled aspects of cell morphology and that evolutionary movement of genes in and out of the Wor1/Mit1/Ryp1 regulon is responsible, in part, for the differences of morphological forms among these species. Consistent with this idea, ectopic expression of C. albicans Wor1 or H. capsulatum Ryp1 can drive the pseudohyphal growth program in S. cerevisiae.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE32550 | GEO | 2011/10/04

SECONDARY ACCESSION(S): PRJNA154461

REPOSITORIES: GEO

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A conserved transcriptional regulator governs fungal morphology in widely diverged species [ChIP-chip, Transcriptional regulation by Mit1 and orthologs]

Project description:In this paper, we examine orthologs of a transcriptional regulator in three fungal species, Saccharomyces cerevisiae, Candida albicans, and Histoplasma capsulatum. We show that, despite an estimated 600 million years since those species diverged from a common ancestor, Wor1 in C. albicans, Ryp1 in H. capsulatum, and Mit1 in S. cerevisiae recognize the same DNA motif. Previous work established that Wor1 regulates white-opaque switching in C. albicans and that its ortholog Ryp1 regulates the yeast to mycelial transition in H. capsulatum. Here we show that the ortholog Mit1 in S. cerevisiae also regulates a morphological transition, in this case pseudohyphal growth. Full genome chromatin immunoprecipitation experiments show that Mit1 binds to the control regions of approximately 94 genes including the previously known regulators of pseudohyphal growth. Through a comparison of full genome chromatin immunoprecipitation experiments for Mit1 in S. cerevisiae, Wor1 in C. albicans, and Wor1 ectopically expressed in S. cerevisiae, we conclude that genes controlled by the orthologous regulators overlap only slightly between these two species. We suggest that the ancestral Wor1/Mit1/Ryp1 protein controlled aspects of cell morphology and that evolutionary movement of genes in and out of the Wor1/Mit1/Ryp1 regulon is responsible, in part, for the differences of morphological forms among these species. Consistent with this idea, ectopic expression of C. albicans Wor1 or H. capsulatum Ryp1 can drive the pseudohyphal growth program in S. cerevisiae.

2011-10-04 | GSE32557 | GEO

A conserved transcriptional regulator governs fungal morphology in widely diverged species [ChIP-chip, Transcriptional regulation by Mit1 and orthologs]

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Project description:The yeast-filament transition is essential for the virulence of a variety of fungi that are pathogenic to humans. N-acetylglucosamine (GlcNAc), a ubiquitous molecule in both the environment and host, is one of the most potent inducers of filamentation in Candida albicans and thermally dimorphic fungi such as Histoplasma capsulatum and Blastomyces dermatitidis. However, GlcNAc suppresses rather than promotes filamentation in Candida tropicalis, a fungal species that is closely related to C. albicans. Furthermore, we discover that glucose induces filamentous growth in C. tropicalis. Mutation and overexpression assays demonstrate that the conserved cAMP signaling pathway plays a central role in the regulation of filamentation in C. tropicalis. Activation of this pathway promotes filamentation in C. tropicalis, while inactivation of this pathway results in a serious growth defect in filamentation. By screening an overexpression library of 154 transcription factors, we have identified approximately 40 regulators of filamentous growth in C. tropicalis. Although most of the regulators (e.g., Tec1, Gat2, Nrg1, Sfl1, Sfl2, and Ash1) demonstrate a conserved role in the regulation of filamentation, similar to their homologs in C. albicans or S. cerevisiae, some of them are specific to C. tropicalis. For example, Czf1 and Efh1 repress filamentation, while Wor1, Zcf3, and Hcm1 promote filamentation in C. tropicalis. Bcr1, Aaf1, and Csr1 play a specific role in the process of GlcNAc-regulated filamentation. Our findings indicate that multiple interconnected signaling pathways are involved in the regulation of filamentation in C. tropicalis. These mechanisms have conserved and divergent features among different Candida species. Total RNA profiles of cells grown in Lee's glucose or Lee's GlcNAc medium.

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Passage through the mammalian gut triggers a phenotypic switch required for Candida albicans commensalism

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The SR protein kinase Sky2 is involved in regulation of dipeptide transport in Candida albicans

Project description:Metabolic adaption to different host niches is one of the most important virulence traits of human fungal pathogens. The metabolic versatility of fungi and other cellular processes such as proliferation, morphogenesis and stress responses are tightly regulated by complex networks in which protein kinases play a crucial role. Serine-arginine (SR) protein kinases are highly conserved in all eukaryotes, but their function in pathogenic Candida spp. has not yet been investigated. C. albicans genome encodes two (Sky1, Sky2) and Candida glabrata one (Sky1) homolog of the human SR protein kinase 1 (SRPK1). We utilized deletion strains of the respective genes in both fungi in order to examine their cellular functions. C. glabrata and C. albicans strains lacking SKY1 exhibited higher resistance to osmotic stress and toxic polyamine concentrations to their ortholog in the model yeast Saccharomyces cerevisiae Sky1. Deletion of SKY2 in C. albicans resulted in impaired utilization of dipeptides as the sole nitrogen source. Subsequent phosphoproteomic analysis identified Ptr22, a transporter of di- and tri-peptides in C. albicans, as a potential Sky2 substrate. Overexpression of PTR22 in the sky2∆ restored the ability to grow on dipeptides as the sole nitrogen source and rendered the cells more susceptible to the dipeptide antibiotics Polyoxin D and Nikkomycin Z. Altogether, our results demonstrate that the two SR-like protein kinases in C. albicans have divergent functions: C. albicans and C. glabrata Sky1 is functionally similar to Sky1 in S. cerevisiae, whereas Sky2 regulates uptake of dipeptides.

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