The Roles of Chromatin Accessibility in Regulating the Candida albicans White-Opaque Phenotypic Switch

Abstract

Candida albicans, a diploid polymorphic fungus, has evolved a unique heritable epigenetic program that enables reversible phenotypic switching between two cell types, referred to as "white" and "opaque". These cell types are established and maintained by distinct transcriptional programs that lead to differences in metabolic preferences, mating competencies, cellular morphologies, responses to environmental signals, interactions with the host innate immune system, and expression of approximately 20% of genes in the genome. Transcription factors (defined as sequence specific DNA-binding proteins) that regulate the establishment and heritable maintenance of the white and opaque cell types have been a primary focus of investigation in the field; however, other factors that impact chromatin accessibility, such as histone modifying enzymes, chromatin remodelers, and histone chaperone complexes, also modulate the dynamics of the white-opaque switch and have been much less studied to date. Overall, the white-opaque switch represents an attractive and relatively "simple" model system for understanding the logic and regulatory mechanisms by which heritable cell fate decisions are determined in higher eukaryotes. Here we review recent discoveries on the roles of chromatin accessibility in regulating the C. albicans white-opaque phenotypic switch.

Keywords: Candida albicans; cell fate decisions; chromatin; chromatin remodeling enzymes; epigenetics; heritability; histone chaperone complexes; histone modifying enzymes; transcriptional regulation; white-opaque switching.

Figure 1

Core white and opaque transcriptional circuits. Colored lines indicate direct binding interactions between each TF (same color as their circular node) and their respective target genes within the white (A) and opaque (B) circuits. Data to create this figure was obtained from [4,9,22,23,25,27]. Figure was generated using Cytoscape [31].

Figure 2

Roles of chromatin modifying enzymes in regulating the C. albicans white-opaque switch. White to opaque and opaque to white switching is indicated by the central black arrows. Smaller black arrows indicate proteins that act to promote switching in the white to opaque direction (upper left quadrant) or in the opaque to white direction (lower left quadrant), while black lines with crossbar indicate proteins that repress switching in the white to opaque direction (upper right quadrant) or in the opaque to white direction (lower right quadrant). Erasers are shown as blue hexagons, writers are shown as aqua ovals, chromatin remodelers are shown as red triangles, and histone chaperones are shown as orange rectangles. Note that Yng2 is a subunit of the NuA4 complex and that Cac2 is a subunit of the CAF-1 complex. *Pho13 has been shown to lack protein phosphatase activity and is instead involved in metabolism [159,160].

Figure 3

Summary illustration of the roles of chromatin regulating proteins in modulating the C. albicans white-opaque switch. Colored lines within the core white and opaque transcriptional circuits indicate direct binding interactions between each TF (same color as their circular node) and their respective target genes. Data to create the transcriptional circuits was obtained from [4,9,22,23,25,27]. Transcriptional circuits were generated using Cytoscape [31]. White to opaque and opaque to white switching is indicated by the central black arrows. Erasers are shown as blue hexagons, writers are shown as aqua ovals, chromatin remodelers are shown as red triangles, and histone chaperones are shown as orange rectangles. Note that Yng2 is a subunit of the NuA4 complex and that Cac2 is a subunit of the CAF-1 complex. *Pho13 has been shown to lack protein phosphatase activity and is instead involved in metabolism [159,160].