title: Identification and Characterization of Wor4, a New Transcriptional Regulator of White-Opaque Switching.
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 circuit of feedback loops that remains excited through many cell divisions. The identification of a new, central regulator of white-opaque switching supports this idea by indicating that the white-opaque switching mechanism is considerably more complex than those controlling conventional, nonheritable patterns of gene expression.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, California 94158.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Lohse
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, California 94158 Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158 ajohnson@cgl.ucsf.edu.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Johnson
mesh_terms: D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism*; D002177:Candidiasis / Q000382:microbiology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000066630:Ectopic Gene Expression; D015966:Gene Expression Regulation, Fungal; D016366:Open Reading Frames; D010641:Phenotype; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D017384:Sequence Deletion; D014158:Transcription, Genetic; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins
keywords: Candida albicans; transcription networks; transcriptional circuits; transcriptional regulation; white-opaque switching