Upc2p, a transcription factor of the zinc cluster family, is an important 
regulator of sterol biosynthesis and azole drug resistance in Candida albicans. 
To better understand Upc2p function in C. albicans, we used genomewide location 
profiling to identify the transcriptional targets of Upc2p in vivo. A triple 
hemagglutinin epitope, introduced at the C terminus of Upc2p, conferred a 
gain-of-function effect on the fusion protein. Location profiling identified 202 
bound promoters (P < 0.05). Overrepresented functional groups of genes whose 
promoters were bound by Upc2p included 12 genes involved in ergosterol 
biosynthesis (NCP1, ERG11, ERG2, and others), 18 genes encoding ribosomal 
subunits (RPS30, RPL32, RPL12, and others), 3 genes encoding drug transporters 
(CDR1, MDR1, and YOR1), 4 genes encoding transcription factors (INO2, ACE2, 
SUT1, and UPC2), and 6 genes involved in sulfur amino acid metabolism (MET6, 
SAM2, SAH1, and others). Bioinformatic analyses suggested that Upc2p binds to 
the DNA motif 5'-VNCGBDTR that includes the previously characterized Upc2p 
binding site 5'-TCGTATA. Northern blot analysis showed that increased binding 
correlates with increased expression for the analyzed Upc2p targets (ERG11, 
MDR1, CDR1, YOR1, SUT1, SMF12, and CBP1). The analysis of ERG11, MDR1, and CDR1 
transcripts in wild-type and upc2Delta/upc2Delta strains grown under 
Upc2p-activating conditions (lovastatin treatment and hypoxia) showed that Upc2p 
regulates its targets in a complex manner, acting as an activator or as a 
repressor depending upon the target and the activating condition. Taken 
together, our results indicate that Upc2p is a key regulator of ergosterol 
metabolism. They also suggest that Upc2p may contribute to azole resistance by 
regulating the expression of drug efflux pump-encoding genes in addition to 
ergosterol biosynthesis genes.