A paper in PLoS Biology from Sandy Johnson’s lab entitled “Interlocking Transcriptional Feedback Loops Control White-Opaque Switching in Candida albicans“ discusses phenotype switching in the human pathogenic fungus Candida albicans. Why is the important?
“White-opaque switching is an epigenetic phenomenon, where genetically identical cells can exist in two distinctive cell types, white and opaque. Each cell type is stably inherited for many generations, and switching between the two types of cells occurs stochastically and rarely—roughly one switch in 10^4 cell divisions”
There is also a review by Kira O’Day to discuss the implications of the findings. Understanding this sort of developmental and epigenetic signaling is important to better know how fungi adjust and interact with their environment. However, the authors do conclude that White-Opaque switching is exclusive to Candida albicans so aspects of this research only directly applicable to studies in this system. Phenotype switching is an active area of research for Candida biologists – some nice micrographs and SEM of the different cell morphologies can be seen at Prof. Joachim Morschhäuser’s page (and linked to the right).
The authors find that roughly 400 genes have differential expression between the white and opaque stages. It was known that WOR1 is a master regulator of this switching based on KO experiments. This study included ChIP-chip analyses that determined that at least 15% of the downstream genes are directly regulated by WOR1.
The authors present the following model of interactions (Figure 4) and feedback loops after untangling the expression and whole-genome DNA binding data. The white or opaque status is stable for several generations of cells (daughter cells formed by budding). The authors conclude that this sort of feedback loops provides insight into how a complicated regulatory feedback system could evolve so that a cell can stably maintain a distinct cell-types for several later generations.