Saccharomyces cerevisiae ergosterol biosynthesis, like cholesterol biosynthesis 
in mammals, is regulated at the transcriptional level by a sterol feedback 
mechanism. Yeast studies defined a 7-bp consensus sterol-response element (SRE) 
common to genes involved in sterol biosynthesis and two transcription factors, 
Upc2 and Ecm22, which direct transcription of sterol biosynthetic genes. The 
7-bp consensus SRE is identical to the anaerobic response element, AR1c. Data 
indicate that Upc2 and Ecm22 function through binding to this SRE site. We now 
show that it is two novel anaerobic AR1b elements in the UPC2 promoter that 
direct global ERG gene expression in response to a block in de novo ergosterol 
biosynthesis, brought about by antifungal drug treatment. The AR1b elements are 
absolutely required for auto-induction of UPC2 gene expression and protein and 
require Upc2 and Ecm22 for function. We further demonstrate the direct binding 
of recombinant expressed S. cerevisiae ScUpc2 and pathogenic Candida albicans 
CaUpc2 and Candida glabrata CgUpc2 to AR1b and SRE/AR1c elements. Recombinant 
endogenous promoter studies show that the UPC2 anaerobic AR1b elements act in 
trans to regulate ergosterol gene expression. Our results indicate that Upc2 
must occupy UPC2 AR1b elements in order for ERG gene expression induction to 
take place. Thus, the two UPC2-AR1b elements drive expression of all ERG genes 
necessary for maintaining normal antifungal susceptibility, as wild type cells 
lacking these elements have increased susceptibility to azole antifungal drugs. 
Therefore, targeting these specific sites for antifungal therapy represents a 
novel approach to treat systemic fungal infections.