G ₁ /S Transcription Factor Orthologues Swi4p and Swi6p Are Important but Not Essential for Cell Proliferation and Influence Hyphal Development in the Fungal Pathogen Candida albicans

Abstract

The G 1 /S transition is a critical control point for cell proliferation and involves essential transcription complexes termed SBF and MBF in Saccharomyces cerevisiae or MBF in Schizosaccharomyces pombe. In the fungal pathogen Candida albicans, G 1 /S regulation is not clear. To gain more insight into the G 1 /S circuitry, we characterized Swi6p, Swi4p and Mbp1p, the closest orthologues of SBF (Swi6p and Swi4p) and MBF (Swi6p and Mbp1p) components in S. cerevisiae. The mbp1⌬/⌬ cells showed minor growth defects, whereas swi4⌬/⌬ and swi6⌬/⌬ yeast cells dramatically increased in size, suggesting a G 1 phase delay. Gene set enrichment analysis (GSEA) of transcription profiles revealed that genes associated with G 1 /S phase were significantly enriched in cells lacking Swi4p and Swi6p. These expression patterns suggested that Swi4p and Swi6p have repressing as well as activating activity. Intriguingly, swi4⌬/⌬ swi6⌬/⌬ and swi4⌬/⌬ mbp1⌬/⌬ strains were viable, in contrast to the situation in S. cerevisiae, and showed pleiotropic phenotypes that included multibudded yeast, pseudohyphae, and intriguingly, true hyphae. Consistently, GSEA identified strong enrichment of genes that are normally modulated during C. albicans-host cell interactions. Since Swi4p and Swi6p influence G 1 phase progression and SBF binding sites are lacking in the C. albicans genome, these factors may contribute to MBF activity. Overall, the data suggest that the putative G 1 /S regulatory machinery of C. albicans contains novel features and underscore the existence of a relationship between G 1 phase and morphogenetic switching, including hyphal development, in the pathogen.

Identification and Functional Characterization of Rca1, a Transcription Factor Involved in both Antifungal Susceptibility and Host Response in Candida albicans

“…These were the mutant for orf19.6011 (SIN3, a putative corepressor of transcription from RNA polymerase II [57]), the mutant for orf19.4545 (SWI4, a TF involved in cell cycle progression [31]), the mutant for orf19.5871 (putative ortholog of S. cerevisiae Swi/Snf component), the mutant for orf19.422 (SPT20, a leucine zipper-containing TF putatively a member of the SAGA complex), and mutants for orf19.5328 (GCN1) and orf19.6904 (GCN3), which are putatively involved in translational mechanisms.…”

Deciphering the Transcriptional-Regulatory Network of Flocculation in Schizosaccharomyces pombe

“…However, it is unlikely that Yox1 regulates the pfl + genes directly because previous chIP-chip analysis did not detect binding of Yox1 to the promoters of pfl + genes [36]. Although there has been solid evidence linking yeast morphogenesis events such as pseudohyphal and hyphal growth to cell cycle regulators [42]–[47], the relationship between cell cycle control and flocculation remains unclear. A flocculation function for yox1 + has not been reported in other yeasts.…”

Phenotypic Consequences of a Spontaneous Loss of Heterozygosity in a Common Laboratory Strain of Candida albicans

“…Finally, MBP1 (orf19.5855 ) encodes a transcription factor that, together with Swi6, forms MBF to regulate genes involved in DNA replication and repair during the cell cycle and following MMS treatment in S. cerevisae (Travesa et al 2012, and references therein). In C. albicans, MBP1 has six nonsynonymous SNPs, and null mutants have minor growth defects under normal conditions (Hussein et al 2011). We hypothesized that MMS sensitivity may result from a defective MBP1 allele.…”