Figure 9.

Sterol precursor(s) lead to Upc2-facilitated induction of Set4 to repress genes required for antifungal drug resistance and sterol homeostasis under hypoxic conditions. (A) Model under hypoxia: Sterol-facilitated induction of Set4 by Upc2 mediates repression of ERG genes by association with the transcriptional repressors Hap1 and Tup1 to block the function of the transcriptional activator, Upc2. Hap1 under hypoxic conditions is heme independent and is considered a transcriptional repressor. Activation of ERG genes by Upc2 is blocked by the presence of Set4 and Hap1 as indicated by the inhibitory symbol. S288C strains expressing the hap1–Ty1 gene fusion partially repress ERG gene expression; whereas yeast strains expressing HAP1 will fully repress ERG genes. (B) Model under azole drug treatment: Sterol-facilitated induction of Set4 by Upc2 mediates repression of genes involved in azole resistance and likely associates with a transcriptional repressor (T.R.) to block a transcriptional activator (T.A.). Under azole treatment, ERG genes are Set4 independent but are activated by Upc2, Hap1^heme, and coactivators. Hap1 under aerobic conditions is bound to heme and is considered a transcriptional activator.