Transcription factor Znf2 coordinates with the chromatin remodeling SWI/SNF complex to regulate differentiation in Cryptococcus neoformans

Cellular differentiation is instructed by development regulators in coordination with chromatin remodeling complexes. Much information about their coordination comes from studies in the model ascomycetous yeasts. It is not clear, however, of the kind of information that can be extrapolated to species of other phyla in Kingdom Fungi. In the basidiomycete Cryptococcus neoformans, the transcription factor Znf2 controls yeast-to-hypha differentiation. Through a forward genetic screen, we identified the basidiomycete-specific factor Brf1 and discovered that it works together with Snf5 in the SWI/SNF chromatin remodeling complex in concert with existent Znf2 to execute cellular differentiation. We demonstrated that SWI/SNF assists Znf2 opening up the promoter regions of hyphal specific genes, including the ZNF2 gene itself. In addition, this complex supports Znf2 to fully associate with its target regions. Importantly, our findings revealed key differences in composition and biological function of the SWI/SNF complex in the two major phyla of Kingdom Fungi. This study involves ATAC and ChIP-Seq.