FIGURE 3.

Regulation of cyp51A expression in A. fumigatus. In azole susceptible isolates, two SRE elements and one CBC binding motif is present in the promoter region of cyp51A. Binding of SrbA to SREs positively regulates cyp51A expression while binding of the CBC to the CGAAT motif negatively regulates expression. Azole challenge (arrow) also positively regulates cyp51a expression. In strains containing either a TR34 promoter repeat or TR46 promoter repeat, SRE elements and CBC binding motifs are duplicated and SrbA effectively binds SREs in the duplicated region, thereby increasing cyp51A expression. Mutation in the HapE (P88L) subunit of the CBC lowers the affinity of the CBC to the CGAAT motif thereby inhibiting negative regulation of cyp51A expression. Solid lines depict experimentally validated results, whereas dotted lines indicate hypotheses which need further validation. Importantly, additional regulatory factors are likely in play at this important gene promoter.