title: Structure of the transcriptional network controlling white-opaque switching in Candida albicans.
abstract: The human fungal pathogen Candida albicans can switch between two phenotypic cell types, termed 'white' and 'opaque'. Both cell types are heritable for many generations, and the switch between the two types occurs epigenetically, that is, without a change in the primary DNA sequence of the genome. Previous work identified six key transcriptional regulators important for white-opaque switching: Wor1, Wor2, Wor3, Czf1, Efg1, and Ahr1. In this work, we describe the structure of the transcriptional network that specifies the white and opaque cell types and governs the ability to switch between them. In particular, we use a combination of genome-wide chromatin immunoprecipitation, gene expression profiling, and microfluidics-based DNA binding experiments to determine the direct and indirect regulatory interactions that form the switch network. The six regulators are arranged together in a complex, interlocking network with many seemingly redundant and overlapping connections. We propose that the structure (or topology) of this network is responsible for the epigenetic maintenance of the white and opaque states, the switching between them, and the specialized properties of each state.
authors.affiliation: Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, 94158, USA.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Hernday
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Lohse
authors.forename: Polly M
authors.initials: PM
authors.lastname: Fordyce
authors.forename: Clarissa J
authors.initials: CJ
authors.lastname: Nobile
authors.forename: Joseph L
authors.initials: JL
authors.lastname: DeRisi
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Johnson
mesh_terms: D002176:Candida albicans / Q000235:genetics* / Q000254:growth & development*; D047369:Chromatin Immunoprecipitation; D004271:DNA, Fungal / Q000378:metabolism; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D044085:Microfluidics; D008954:Models, Biological; D010641:Phenotype; D011485:Protein Binding
chemical_list: D004271:DNA, Fungal