scholarly journals Global Roles of Ssn6 in Tup1- and Nrg1-dependent Gene Regulation in the Fungal Pathogen,Candida albicans

2005 ◽  
Vol 16 (6) ◽  
pp. 2913-2925 ◽  
Author(s):  
Susana García-Sánchez ◽  
Abigail L. Mavor ◽  
Claire L. Russell ◽  
Silvia Argimon ◽  
Paul Dennison ◽  
...  

In budding yeast, Tup1 and Ssn6/Cyc8 form a corepressor that regulates a large number of genes. This Tup1-Ssn6 corepressor appears to be conserved from yeast to man. In the pathogenic fungus Candida albicans, Tup1 regulates cellular morphogenesis, phenotypic switching, and metabolism, but the role of Ssn6 remains unclear. We show that there are clear differences in the morphological and invasive phenotypes of C. albicans ssn6 and tup1 mutants. Unlike Tup1, Ssn6 depletion promoted morphological events reminiscent of phenotypic switching rather than filamentous growth. Transcript profiling revealed minimal overlap between the Ssn6 and Tup1 regulons. Hypha-specific genes, which are repressed by Tup1 and Nrg1, were not derepressed in ssn6 cells under the conditions studied. In contrast, the phase specific gene WH11 was derepressed in ssn6 cells, but not in tup1 or nrg1 cells. Hence Ssn6 and Tup1 play distinct roles in C. albicans. Nevertheless, both Ssn6 and Tup1 were required for the Nrg1-mediated repression of an artificial NRE promoter, and lexA-Nrg1 mediated repression in the C. albicans one-hybrid system. These observations are explained in models that are generally consistent with the Tup1-Ssn6 paradigm in budding yeast.

2018 ◽  
Author(s):  
Prashant R. Desai ◽  
Klaus Lengeler ◽  
Mario Kapitan ◽  
Silas Matthias Janßen ◽  
Paula Alepuz ◽  
...  

ABSTRACTExtensive 5’ untranslated regions (UTR) are a hallmark of transcripts determining hyphal morphogenesis inCandida albicans.The major transcripts of theEFG1gene, which are responsible for cellular morphogenesis and metabolism, contain a 5’ UTR of up to 1170 nt. Deletion analyses of the 5’ UTR revealed a 218 nt sequence that is required for production of the Efg1 protein and its functions in filamentation, without lowering the level and integrity of theEFG1transcript. Polysomal analyses revealed that the 218 nt 5’ UTR sequence is required for efficient translation of the Efg1 protein. Replacement of theEFG1ORF by the heterologous reporter geneCaCBGlucconfirmed the positive regulatory importance of the identified 5’ UTR sequence. In contrast to other reported transcripts containing extensive 5’ UTR sequences, these results indicate the positive translational function of the 5’ UTR sequence in theEFG1transcript, which is observed in context of the nativeEFG1promoter. The results suggest that the 5’ UTR recruits regulatory factors, possibly during emergence of the native transcript, which aid in translation of theEFG1transcript.IMPORTANCEMany of the virulence traits that makeCandida albicansan important human fungal pathogen are regulated on a transcriptional level. Here we report an important regulatory contribution of translation, which is exerted by the extensive 5’ untranslated regulatory sequence (5’ UTR) of the transcript for the protein Efg1, which determines growth, metabolism and filamentation in the fungus. Presence of the 5’ UTR is required for efficient translation of Efg1, to promote filamentation. Because transcripts for many relevant regulators contain extensive 5’ UTR sequences, it appears that virulence ofC. albicansdepends on the combination of transcriptional and translation regulatory mechanisms.


mBio ◽  
2021 ◽  
Author(s):  
Thomas P. Conway ◽  
Kayla Conway ◽  
Frank A. Boksa ◽  
Claude Pujol ◽  
Deborah Wessels ◽  
...  

Candida albicans , the most pervasive fungal pathogen colonizing humans, undergoes a phenotypic transition between a white and opaque phenotype. The unique opaque phenotype is necessary for mating and colonization of the lower gastrointestinal tract.


1995 ◽  
Vol 73 (S1) ◽  
pp. 1049-1057 ◽  
Author(s):  
David R. Soll ◽  
Thyagarajan Srikantha ◽  
Brian Morrow ◽  
Anand Chandrasekhar ◽  
Klaus Schröppel ◽  
...  

Most strains of Candida albicans switch frequently and reversibly among a number of different phenotypes distinguishable by colony morphology. Previous experiments indicated that switching involved differential gene expression. Using the white–opaque transition as a model switching system, we have cloned two opaque-specific genes, PEP1 and OP4, and one white specific gene, WH11. Differential transcription of these genes suggested that switching involves the coordinate regulation of batteries of unlinked phase-specific genes. It has been demonstrated that the frequency of integration at phase specific loci is a function of the transcriptional state of the phase-specific genes. In addition, a functional dissection of the 5′-upstream region of the WH11 gene has identified two major domains containing cis-acting regulatory sequences that are involved in phase-specific transcription. Gel retardation experiments provide evidence for white phase-specific trans-acting factors which form complexes with both domains. The regulation of the switching event is discussed. Key words: Candida albicans, phenotypic switching, white–opaque transition, phase-specific genes, integrative transformation, promoter regions, WH11 gene.


2007 ◽  
Vol 6 (4) ◽  
pp. 693-709 ◽  
Author(s):  
Samin Kim ◽  
Michael J. Wolyniak ◽  
Janet F. Staab ◽  
Paula Sundstrom

ABSTRACT To elucidate the molecular mechanisms controlling the expression of the hypha-specific adhesin gene HWP1 of Candida albicans, its promoter was dissected and analyzed using a green fluorescent protein reporter gene. A 368-bp region, the HWP1 control region (HCR), was critical for activation under hypha-inducing conditions and conferred developmental regulation to a heterologous ENO1 promoter. A more distal region of the promoter served to amplify the level of promoter activation. Using gel mobility shift assays, a 249-bp subregion of HCR, HCRa, was found to bind at least four proteins from crude extracts of yeasts and hyphae with differing binding patterns dependent on cell morphology. Four proteins with DNA binding activities were identified by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis after separation by anion-exchange and heparin-Sepharose chromatography. One protein with high similarity to Nhp6, an HMG1 family member in Saccharomyces cerevisiae, and another with weak similarity to an HMG-like condensation factor from Physarum polycephalum implicated changes in chromatin structure as a critical process in hypha-specific gene regulation. Proteins with strong homology to histones were also found. These studies are the first to identify proteins that bind to a DNA segment that confers developmental gene regulation in C. albicans and suggest a new model for hypha-specific gene regulation.


2003 ◽  
Vol 2 (6) ◽  
pp. 1350-1360 ◽  
Author(s):  
Sneh L. Panwar ◽  
Melanie Legrand ◽  
Daniel Dignard ◽  
Malcolm Whiteway ◽  
Paul. T. Magee

ABSTRACT Candida albicans, the single most frequently isolated human fungal pathogen, was thought to be asexual until the recent discovery of the mating-type-like locus (MTL). Homozygous MTL strains were constructed and shown to mate. Furthermore, it has been demonstrated that opaque-phase cells are more efficient in mating than white-phase cells. The similarity of the genes involved in the mating pathway in Saccharomyces cerevisiae and C. albicans includes at least one gene (KEX2) that is involved in the processing of the α mating pheromone in the two yeasts. Taking into account this similarity, we searched the C. albicans genome for sequences that would encode the α pheromone gene. Here we report the isolation and characterization of the gene MFα1, which codes for the precursor of the α mating pheromone in C. albicans. Two active α-peptides, 13 and 14 amino acids long, would be generated after the precursor molecule is processed in C. albicans. To examine the role of this gene in mating, we constructed an mfα1 null mutant of C. albicans. The mfα1 null mutant fails to mate as MTLα, while MTLa mfα1 cells are still mating competent. Experiments performed with the synthetic α-peptides show that they are capable of inducing growth arrest, as demonstrated by halo tests, and also induce shmooing in MTLa cells of C. albicans. These peptides are also able to complement the mating defect of an MTLα kex2 mutant strain when added exogenously, thereby confirming their roles as α mating pheromones.


1970 ◽  
Vol 12 (4) ◽  
pp. 934-940 ◽  
Author(s):  
L. T. Kirby ◽  
E. D. Styles

A number of genes are known to be involved in the production of anthocyanin in maize aleurone. Thin layer chromatography has been used to detect specific flavonoids associated with the recessive forms of these genes. The results obtained so far indicate that the genes C1, C2, R and Pr all act before the formation of flavonol in the biosynthetic pathway, that A1 acts between flavanonol and 'flavenol' and that A2 acts between flavenol and anthocyanidin. Light substitutes for the action of the C1 gene in certain conditions and can be used to 'force' the system, causing a buildup of intermediate and side products beyond the C1 controlled step. The C1 gene probably controls a step between the C9 stage and flavanone.


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