FIG 7.

Schematic summarizing the key findings of the study. Under regular growth conditions, the FK506-binding proteins CgFpr3 and CgFpr4 maintain histone H3 and H4 levels and negatively regulate the CgPDR1 regulon, viz., the expression of the CgPDR1, CgCDR1, CgCDR2, and CgSNQ2 genes. Contrarily, CgRph1, a putative histone demethylase, positively regulates the CgPDR1 regulon. Of note, the underlying mechanism(s) is yet to be elucidated. Furthermore, in response to fluconazole exposure or upon the simultaneous deletion of the CgFPR3 and CgFPR4 genes, histone H3 and H4 protein levels are elevated, probably leading to differential acetylation and/or methylation of H3 and H4 (represented by blue nucleosomes), and the CgPDR1 regulon is activated, resulting in the increased expression of the CgPDR1, CgCDR1, CgCDR2, and CgSNQ2 genes. This activation of MDR genes is pivotal to the survival of fluconazole stress in C. glabrata. Of note, the loss of the CgFPR3 and CgFPR4 genes leading to an open chromatin state at the CgPDR1 promoter is yet to be demonstrated experimentally.