Genome-wide mapping of the coactivator Ada2p yields insight into the functional roles of SAGA/ADA complex in Candida albicans.
The SAGA/ADA coactivator complex, which regulates numerous cellular processes by coordinating histone acetylation, is widely conserved throughout eukaryotes, and analysis of the Candida albicans genome identifies the components of this complex in the fungal pathogen. We investigated the multiple functions of SAGA/ADA in C. albicans by determining the genome-wide occupancy of Ada2p using chromatin immunoprecipitation (ChIP). Ada2p is recruited to 200 promoters upstream of genes involved in different stress-response functions and metabolic processes. Phenotypic and transcriptomic analysis of ada2 mutant showed that Ada2p is required for the responses to oxidative stress, as well as to treatments with tunicamycin and fluconazole. Ada2p recruitment to the promoters of oxidative resistance genes is mediated by the transcription factor Cap1p, and coactivator function were also established for Gal4p, which recruits Ada2p to the promoters of glycolysis and pyruvate metabolism genes. Cooccupancy of Ada2p and the drug resistance regulator Mrr1p on the promoters of core resistance genes characterizing drug resistance in clinical strains was also demonstrated. Ada2p recruitment to the promoters of these genes were shown to be completely dependent on Mrr1p. Furthermore, ADA2 deletion causes a decrease in H3K9 acetylation levels of target genes, thus illustrating its importance for histone acetyl transferase activity.
Sellam
Adnane
A
Biotechnology Research Institute, National Research Council of Canada, Montréal, QC, H4P 2R2, Canada.
Askew
Christopher
C
Epp
Elias
E
Lavoie
Hugo
H
Whiteway
Malcolm
M
Nantel
André
A
D000107:Acetylation / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D002874:Chromosome Mapping; D025141:Drug Resistance, Fungal / Q000187:drug effects; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal; D016681:Genome, Fungal / Q000235:genetics*; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics; D006657:Histones / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D046912:Multiprotein Complexes / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D017510:Protein Folding / Q000187:drug effects; D019289:Pyruvic Acid / Q000378:metabolism; D014774:Virulence / Q000187:drug effects
D005656:Fungal Proteins; D006657:Histones; D046912:Multiprotein Complexes; D019289:Pyruvic Acid; D015725:Fluconazole