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Structure of the transcriptional network controlling white‐opaque switching in C andida albicans
Author(s) -
Hernday Aaron D.,
Lohse Matthew B.,
Fordyce Polly M.,
Nobile Clarissa J.,
DeRisi Joseph L.,
Johnson Alexander D.
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12329
Subject(s) - biology , phenotypic switching , genetics , chromatin , epigenetics , gene , genome , gene regulatory network , computational biology , phenotype , gene expression
Summary The human fungal pathogen C andida 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.