Analyzing the Candida albicans Transcriptional Program Shortly After Hypha Induction




Hernandez, Karen R.

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Candida albicans is an opportunistic fungal pathogen that is part of the human microbiota, growing mainly on the mucosal surfaces of the gastrointestinal and genitourinary tracts. Its ability to change from yeast to hyphae plays a critical role in its virulence. This change in cellular morphology is negatively regulated by the transcriptional repressor Nrg1 and induced to varying degrees by an assortment of transcription factors, including Brg1, Ume6, Efg1, Cph1, Flo8 and others. Upon hyphal induction, BRG1 expression is rapidly upregulated and simultaneously, NRG1 transcript levels decline. Previous work in our lab uncovered a novel feedback circuit in which Brg1 is required for the induction of an NRG1 antisense transcript that enables filamentation. Currently it is not known whether BRG1 acts directly or indirectly to produce the NRG1 antisense transcript. In order to identify transcription factors that function downstream of Brg1 (since they may play a role in the production of the antisense transcript), we performed RNA-Seq on wild-type (SC5314) and brg1 mutant strains, 15 minutes after hyphal induction. We discovered that the transcription factors Cph1 and Ume6 were differentially upregulated in the wild-type strain. By introducing a regulatable tet-BRG1 allele into cph1Δ and ume6Δ mutant strains, we were able to determine that, while Cph1 plays little if any role in mediating hypha formation downstream of Brg1, Ume6 seems to be heavily involved in this process and therefore its interaction with Brg1 and the induction of the NRG1 antisense transcript warrants further examination.


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Integrative Biology