Identification and Characterization of Wor4, a New Transcriptional Regulator of White-Opaque Switching

G3 : Genes - Genomes - Genetics
Matthew B Lohse, Alexander D Johnson

Abstract

The human fungal pathogen Candida albicans can switch between two cell types, "white" and "opaque," each of which is heritable through many cell divisions. Switching between these two cell types is regulated by six transcriptional regulators that form a highly interconnected circuit with multiple feedback loops. Here, we identify a seventh regulator of white-opaque switching, which we have named Wor4. We show that ectopic expression of Wor4 is sufficient to drive switching from the white to the opaque cell type, and that deletion of Wor4 blocks switching from the white to the opaque cell type. A combination of ectopic expression and deletion experiments indicates that Wor4 is positioned upstream of Wor1, and that it is formally an activator of the opaque cell type. The combination of ectopic expression and deletion phenotypes for Wor4 is unique; none of the other six white-opaque regulators show this pattern. We determined the pattern of Wor4 binding across the genome by ChIP-seq and found it is highly correlated with that of Wor1 and Wor2, indicating that Wor4 is tightly integrated into the existing white-opaque regulatory circuit. We previously proposed that white-to-opaque switching relies on the activation of a complex circ...Continue Reading

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Citations

Nov 22, 2016·Nature Reviews. Microbiology·Suzanne M NobleJessica N Witchley
Jan 18, 2018·Pathogens·Christina Braunsdorf, Salomé LeibundGut-Landmann
Feb 13, 2019·Current Protocols in Microbiology·Corey FrazerRichard J Bennett
Jun 4, 2020·G3 : Genes - Genomes - Genetics·Lucas R BrenesAlexander D Johnson
Nov 5, 2016·Frontiers in Cellular and Infection Microbiology·Pedro PaisMiguel C Teixeira
Mar 10, 2017·Virulence·Thabiso E MotaungToi J Tsilo
Dec 12, 2019·Proceedings of the National Academy of Sciences of the United States of America·Chiraj K DalalAlexander D Johnson
Jan 12, 2021·Frontiers in Cellular and Infection Microbiology·Diana L RodriguezClarissa J Nobile
Sep 28, 2021·Molecular Microbiology·Laxmi Shanker RaiSophie Bachellier-Bassi
Sep 8, 2021·MBio·Thomas P ConwayDavid R Soll

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Datasets Mentioned

BETA
GSE75124

Methods Mentioned

BETA
ChIP-chip
ChIP-seq
PCR
ChIP
immunoprecipitation
RNA-seq

Software Mentioned

Bowtie2
ELM
SPP R Bioconductor package
MochiView
Fungal Genomes Search
HHpred
TBLASTN
BLASTP

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