Expression changes between C. albicans white and opaque cell types and mutant strains
Ontology highlight
ABSTRACT:
ORGANISM(S): Candida albicans
PROVIDER: GSE42134 | GEO | 2013/05/01
SECONDARY ACCESSION(S): PRJNA179193
REPOSITORIES: GEO
Similar Datasets
Project description:The goal of this study is to characterize the transcriptional regulatory network that controls white-opaque cell-type switching in Candida albicans. This dataset includes microarrays comparing expression levels in wild-type white and opaque cell types, as well as 6 different transcription factor deletion strains. All samples were hybridized against a common mixed reference to allow for comparison between any two datasets within this study. Gene expression arrays were performed on wild-type and transcription factor deletion white and opaque a/a cell types . High and low intensity scans were performed. Background and saturated spots were filtered out, as indicated by null. Data from each scan was normalized by lowess normalization to enable transformation across any pair of datasets. All data presented are log2 ratios of Cy5/Cy3 Each sample was hybridized against a mixed reference sample to allow for transformation between any of the individual samples (white vs. opaque, wild-type vs. mutant)
2013-05-01 | E-GEOD-42134 | biostudies-arrayexpress
Project description:As a successful commensal and pathogen of humans, Candida albicans encounters a wide range of environmental changes. Among them, ambient pH is an important factor, which changes frequently and affects many biological processes in this species. The ability to adapt to pH changes is tightly linked with pathogenesis and morphogenesis. In this study, we report that pH has a profound effect on white-opaque switching and sexual mating in C. albicans. Acidic pHs promote white-to-opaque switching but repress sexual mating of opaque cells. The cAMP signaling and Rim101-mediated pH sensing pathways are involved in the regulation of pH-regulated white-opaque switching. Interestingly, white and opaque cells of the cyr1/cyr1 mutant, which is defective in producing cAMP, show distinct growth defects under acidic and alkaline conditions. Phr2 could play a major role in acidic pHs-induced opaque cell formation. We further discover that acidic pH conditions repress sexual mating due to the failure of activation of the Ste2-mediated a-pheromone response pathway. The effects of pH changes on phenotypic switching and sexual mating could be a balance behavior between host adaptation and sexual reproduction.
2015-12-30 | GSE67101 | GEO
Project description: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. Keywords: ChIP-chip
2007-10-01 | GSE8709 | GEO
Project description:The discovery of white-opaque switching in natural MTLa/alpha isolates of Candida albicans sheds new light on the evolution of phenotypic plasticity and host adaptation.
2013-04-01 | GSE43938 | GEO
Project description:In Candida albicans, the a1-alpha2 complex represses white-opaque switching as well as mating. A ChIP-chip strategy was, therefore, used to screen for genes with a1-alpha2 binding sites and expression patterns consistent with a master switch gene (MSG). Of 51 genes identified with an a1-alpha2 binding site, one gene, TOS9, also referred to as EAP2, exhibited an expression pattern consistent with a MSG. TOS9 is expressed in opaque, not white a/a and alpha/alpha cells and Tos9p localizes to the opaque cell nucleus. Deletion of TOS9 blocks cells in the white phase, and misexpression in the white phase of the parent tos9+/tos9+ strain results in mass conversion to opaque. Expression of TOS9 under control of a MET promoter rescues the TOS9 null mutant tos9-/tos9- phenotype. Temperature-induced mass conversion of opaque to white in the parent strain results in the immediate cessation of TOS9 transcription, and loss of Tos9p prior to the point of commitment to white (the switch event), which occurs at the time of the second cell doubling. Misexpression of TOS9, as well as inhibition of the second round of DNA replication inhibits the temperature-induced switch from opaque to white. Based on these observations, a model is developed for the regulation and role of TOS9 in switching. Keywords: ChIP chip
2006-09-19 | GSE5493 | GEO
Project description:The human commensal and opportunistic pathogen Candida albicans can switch between two distinct, heritable cell types, named “white” and “opaque,” which differ in morphology, mating abilities, metabolic preferences, and in their interactions with the host immune system. Previous studies revealed a highly interconnected group of transcriptional regulators that control switching between the two cell types. Here, we identify Ssn6, the C. albicans functional homolog of the Saccharomyces cerevisiae transcriptional co-repressor Cyc8, as a new regulator of white-opaque switching. In a or α mating type strains, deletion of SSN6 results in mass switching from the white to the opaque cell type. Transcriptional profiling of ssn6 deletion mutant strains reveals that Ssn6 represses part of the opaque cell transcriptional program in white cells and the majority of the white cell transcriptional program in opaque cells. Genome-wide chromatin immunoprecipitation experiments demonstrate that Ssn6 is tightly integrated into the opaque cell regulatory circuit and that the positions to which it is bound across the genome strongly overlap with those bound by Wor1 and Wor2, previously identified regulators of white-opaque switching. This work reveals the next layer in the white-opaque transcriptional circuitry by integrating a transcriptional regulator that does not bind DNA directly but instead associates with specific combinations of DNA-bound transcriptional regulators.
2015-12-28 | GSE74011 | GEO
Project description:The discovery of white-opaque switching in natural MTLa/alpha isolates of Candida albicans sheds new light on the evolution of phenotypic plasticity and host adaptation. Comparing gene expression of white and opaque cells of a MTL a/alpha strain
2013-04-01 | E-GEOD-43938 | biostudies-arrayexpress
Project description:The human fungal pathogen Candida albicans can switch between two cell types, âwhiteâ and âopaque,â each of which is heritable through many cell divisions. Switching between these two cell types is regulated by six transcriptional regulators which form a highly interconnected circuit with multiple feedback loops. Here, we identify a seventh regulator of white-opaque switching, which we have named Wor4. We show that ectopic expression of Wor4 is sufficient to drive switching from the white to the opaque cell type and that deletion of Wor4 blocks switching from the white to the opaque cell type. A combination of ectopic expression and deletion experiments indicates that Wor4 is positioned upstream of Wor1 and that it is formally an activator of the opaque cell type. The combination of ectopic expression and deletion phenotypes for Wor4 is unique; none of the other six white-opaque regulators show this pattern. We determined the pattern of Wor4 binding across the genome by ChIP-seq and found it is highly correlated with that of Wor1 and Wor2, indicating that Wor4 is tightly integrated into the existing white-opaque regulatory circuit. We previously proposed that white-to-opaque switching relies on the activation of a complex circuit of feedback loops that remains excited through many cell divisions. The identification of a new, central regulator of white-opaque switching supports this idea by indicating that the white-opaque switching mechanism is considerably more complex than those controlling conventional, non-heritable patterns of gene expression. C. albicans Wor4-GFP versus untagged control in both white and opaque cell types. Cells grown in SD+aa+Uri at 25°C with three technical replicates of each strain/cell type (12 total).
2016-01-11 | E-GEOD-75124 | biostudies-arrayexpress
Project description:The human fungal pathogen Candida albicans can switch between two cell types, “white” and “opaque,” each of which is heritable through many cell divisions. Switching between these two cell types is regulated by six transcriptional regulators which form a highly interconnected circuit with multiple feedback loops. Here, we identify a seventh regulator of white-opaque switching, which we have named Wor4. We show that ectopic expression of Wor4 is sufficient to drive switching from the white to the opaque cell type and that deletion of Wor4 blocks switching from the white to the opaque cell type. A combination of ectopic expression and deletion experiments indicates that Wor4 is positioned upstream of Wor1 and that it is formally an activator of the opaque cell type. The combination of ectopic expression and deletion phenotypes for Wor4 is unique; none of the other six white-opaque regulators show this pattern. We determined the pattern of Wor4 binding across the genome by ChIP-seq and found it is highly correlated with that of Wor1 and Wor2, indicating that Wor4 is tightly integrated into the existing white-opaque regulatory circuit. We previously proposed that white-to-opaque switching relies on the activation of a complex circuit of feedback loops that remains excited through many cell divisions. The identification of a new, central regulator of white-opaque switching supports this idea by indicating that the white-opaque switching mechanism is considerably more complex than those controlling conventional, non-heritable patterns of gene expression.
2016-01-11 | GSE75124 | GEO
Project description:It has been proposed that the ancestral fungus was mating competent and homothallic. However, many mating competent fungi were initially classified as asexual because their mating capacity was hidden behind layers of regulation. For efficient in vitro mating, the essentially obligate diploid ascomycete pathogen C. albicans has to homozygose its mating type locus from MTLa/α to MTLa/a or MTLα/α, and then undergo an environmentally controlled epigenetic switch to the mating competent opaque form. These requirements greatly reduce the potential for C. albicans mating. Deletion of the YciI domain gene OFR1 bypasses the need for C. albicans cells to homozygose the mating type locus prior to switching to the opaque form and mating, and allows homothallic mating of MTL heterozygous strains. This bypass is carbon source dependent and does not occur when cells are grown on glucose. Transcriptional profiling of ofr1 mutant cells shows that in addition to regulating cell type and mating circuitry, Ofr1 is needed for proper regulation of histone and chitin biosynthesis gene expression. It appears that OFR1 is a key regulator in C. albicans, and functions in part to maintain the cryptic mating phenotype of the pathogen. Distruption of OFR1 gene which encodes a Yci1 related domain in Candida ablicans (MTLa/α) is shown to have white-opaque switching related and mating related gene expression. The expression of histone genes are also positively regulated in some conditions.
2015-12-29 | GSE75780 | GEO