UC Merced

Biological switches control cell-fate decisions across biological kingdoms. Many of these cell-fate decisions are controlled by complex transcriptional networks, consisting of unique combinations of transcriptional regulators and their respective cis-regulatory targets. An example of such a network is that which controls the white-opaque phenotypic switch in the human fungal pathogen, Candida albicans. The white-opaque switch gives rise to two distinct cell types – white and opaque – which differ in their mating competence, adaptation to distinct environmental niches, host immune cell evasion, and morphological characteristics at the single-cell and colony level. Each cell type can be heritably maintained through many generations and stochastic or environmentally induced switching can lead to a transition between these two phenotypic states. Switching between these two heritably maintained transcriptional programs occurs without any changes to the primary sequence of the genome, and thus fits the classic definition of an epigenetic switch. The ability of C. albicans to readily switch between the white and opaque phenotypes is controlled by a “core” circuit of eight transcription factors (TFs) that is centered around the opaque-specific master regulator Wor1 (White-Opaque Regulator 1), however, recent work has identified a set of nineteen new regulators that impinge upon the switch. In this work, we characterize these newly identified TFs and their interactions with the previously defined “core” regulators as well as determine how these new regulators affect the establishment and maintenance of the white-opaque switch.