The Caenorhabditis elegans peb-1 gene encodes a novel DNA-Binding protein involved in morphogenesis of the pharynx, vulva, and hindgut

Gene expression in the Caenorhabditis elegans pharynx is regulated in part by organ-specific signals, which in the myo-2 gene target a regulatory sequence called the C subelement. C subelement activity requires the organ specification factor PHA-4 a winged-helix transcription factor expressed in all pharyngeal cells. To identify additional factors involved in pharyngeal organogenesis, we performed a yeast one-hybrid screen for C subelement binding proteins. Here we describe the novel factor FEB-I, which is coexpressed with PHA-4 in many pharyngeal cell types, including muscles, epithelial cells, marginal cells, and glands, but is undetectable in the pharyngeal nervous system. PEB-1 is also detected outside the pharynx in cells surrounding the rectum and vulva, as well as in the germ line. Reduction of peb-1 function using RNAi results in morphological defects in the somatic tissues in which peb-1 is expressed. We have mapped the FEB-I DNA-binding domain to a 158-residue region, which is unrelated to known DNA-binding proteins but shares some sequence similarity to the Drosophila Mod(mdg4) proteins. FEB-I specifically recognizes a site in the C subelement that partially overlaps the PHA-4 binding site. Both the PEB-1 and the PHA-4 binding sites are necessary for strong C subelement enhancer activity in some cells iu which these factors are coexpressed. In contrast the FEB-I site is dispensable for C subelement activity in pharyngeal neurons. We propose that PEB-1 functions with PHA-4 to activate target gene expression in cells in which they are coexpressed. (C) 2000 Academic Press.