Abstract

TATA box-binding protein (TBP)-associated factors (TAFs), evolutionarily conserved from yeast to humans, play a central role during transcription initiation. A subset of TAF proteins is shared in transcription factor II D (TFIID) and SAGA transcription regulatory complexes. Although higher eukaryotes contain multiple TAF variants that specify tissue- and developmental stage-specific organization of TFIID or SAGA complexes, in unicellular genomes, however, each TAF is encoded by a single gene. Surprisingly, we found that the genome of Candida albicans, the predominant human fungal pathogen, contains two paralogous TAF12 genes, CaTAF12L and CaTAF12, encoding H2B-like histone-fold domain-containing variants. Of the available fungal genome sequences, only seven other closely related diploid pathogenic Candida genomes encode the two TAF12 paralogs. Using affinity purifications from C. albicans cell extracts, we demonstrate that CaTAF12L uniquely associates with the SAGA complex and CaTAF12 associates with the TFIID complex. We further show that CaTAF12, but not CaTAF12L, is essential for C. albicans growth. Conditional depletion of the two TAF12 variant proteins caused distinct cellular and colony phenotypes. Together our results define a specialized organization of the TAF12 variants and non-redundant roles for the two TAF12 variants in the unicellular C. albicans genome.

Highlights

  • Initiation of transcription leading to the formation of a preinitiation complex at the core promoter is a critical control point in gene regulation [1]

  • We further show that CaTAF12L is required for oxidative stress resistance of C. albicans

  • To test whether the two C. albicans TAF12 genes could function in the budding yeast Saccharomyces cerevisiae, we expressed the CaTAF12L and CaTAF12 genes from the yeast GAL1 promoter

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Summary

ACCELERATED COMMUNICATION crossmark

Higher eukaryotes contain multiple TAF variants that specify tissue- and developmental stage-specific organization of TFIID or SAGA complexes, in unicellular genomes, each TAF is encoded by a single gene. We found that the genome of Candida albicans, the predominant human fungal pathogen, contains two paralogous TAF12 genes, CaTAF12L and CaTAF12, encoding H2B-like histone-fold domain-containing variants. The diverse spectrum of TBPand TAF-like factors allows the higher eukaryotic cells to form multiple TFIID complexes that differ in their subunit composition, binding specificity, and function [22]. We report that two novel paralogous TAF12 genes, CaTAF12L/orf19.470 and CaTAF12/orf19.6820, have non-redundant functions in Candida albicans, the most predominant fungal pathogen causing invasive candidiasis in humans [29]. We show extract peptone dextrose; YPMal, yeast extract peptone maltose; CFW, calcofluor white; 5-FOA, 5-fluoroorotic acid; Ca, Candida albicans

Vector only
Results
YPMal YPD
Discussion
Experimental procedures
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