Genetic suppressors of C. elegans pha-4/FoxA identify the predicted AAA helicase ruvb-1/RuvB

FoxA transcription factors are critical regulators of gut development and function. FoxA proteins specify gut fate during early embryogenesis, drive gut differentiation and morphogenesis at later stages and impact gut function to mediate nutritional responses. The level of FoxA is critical for these roles, yet we know relatively little about regulators for this family of proteins. To address this issue, we conducted a genetic screen for mutants that suppress a partial loss of pha-4, the sole FoxA factor of C. elegans. We identified 55 mutants using either chemical or insertional mutagenesis. 42 of these were informational suppressors that affected nonsense-mediated decay, while the remaining 13 were pha-4 suppressors. These 13 alleles defined at least 6 different loci. Based on mutational frequencies for C. elegans and the genetic dominance of four of the suppressors, we predict that many of the suppressors are either unusual loss-of-function mutations in negative regulators or rare gain-of-function mutations in positive regulators. We characterized one dominant suppressor molecularly and discovered the mutation alters a likely cis-regulatory region within pha-4 itself. A second suppressor defined a new locus, the predicted AAA+ helicase ruvb-1. These results indicate that our screen successfully found cis or trans-acting regulators of pha-4.

Key Words: Mos1, foregut, gonad, pharynx, suppressor screen

Online ISS 1091-6490
Copyright 2008 by the Genetics Society of America
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