Identification and characterization of a previously undescribed family of sequence-specific DNA-binding domains

• DOI: 10.1073/pnas.1221734110
• Publication Date: 2013-04-23T07:10:22Z
• Authors: Matthew B. Lohse; Aaron D. Hernday; Polly M. Fordyce; Liron Noiman; Trevor R. Sorrells; Victor Hanson-Smith; Clarissa J. Nobile; Joseph L. DeRisi; Alexander D. Johnson
• Keywords: GATA6; DNA binding site; Sequence motif

Sequence-specific DNA-binding proteins are among the most important classes of gene regulatory proteins, controlling changes in transcription that underlie many aspects biology. In this work, we identify a transcriptional regulator from human fungal pathogen Candida albicans binds DNA specifically but has no detectable homology with any previously described DNA- or RNA-binding protein. This protein, named White–Opaque Regulator 3 (Wor3), regulates white–opaque switching, ability C. to switch between two heritable cell types. We demonstrate ectopic overexpression WOR3 results mass conversion white cells opaque and deletion affects stability at physiological temperatures. Genome-wide chromatin immunoprecipitation Wor3 expression profiling wor3 mutant strain indicate is highly integrated into circuit regulating switching it controls subset program. show by biochemical, genetic, microfluidic experiments directly sequence-specific manner, set cis -regulatory sequences recognized Wor3. Bioinformatic analyses family arose more recently evolutionary time than domains; restricted small number fungi include major pathogens humans. These observations new families may be clades suggest current annotations—which rely on deep conservation—underestimate fraction genes coding for regulators.