FIG 9.

Model depicting the role of Set1 contributing to azole susceptibility in a species-specific manner (Biorender). (A and B) Transcriptional activation recruits TFs, RNA polymerase II, and the Set1 complex to increase histone H3K4 methylation and permit proper induction of gene expression. This increase in methylation could also recruitment other cofactors/epigenetic regulators (e.g., Set3 and/or SAGA complex) that contain “reader” domains that recognize and bind to the H3K4 methyl mark to help in expression. In addition, other factors (“X?”) could be utilized to bypass the requirement of Set1. (A) In C. glabrata, azole-resistant genes (ARG) such as efflux pumps and ERG genes are induced upon azole treatment. In Cgset1Δ strains azole induction of ERG gene expression consequently ergosterol levels are decreased, but expression or function efflux pumps are not altered. (B) Under azole-treated conditions, efflux pump expression and function are decreased, but ERG gene expression is induced similar to WT levels.