title: Contribution of the amino and carboxyl termini for PHA-4/FoxA function in Caenorhabditis elegans.
abstract: FoxA transcription factors are central regulators of gut development in all animals that have been studied. Here we examine the sole Caenorhabditis elegans FoxA protein, which is called pha-4. We describe the molecular characterization of five pha-4 mutations and characterize their associated phenotypes. Two nonsense mutations are predicted to truncate PHA-4 after the DNA binding domain and remove the conserved carboxyl terminus. Surprisingly, animals harboring these mutations are viable, provided the mutant mRNAs are stabilized by inactivating the nonsense-mediated decay pathway. Two additional nonsense mutations reveal that the DNA binding domain is critical for activity. A missense mutation predicted to alter the PHA-4 amino terminus leads to a dramatic reduction in pha-4 activity even though the protein is expressed appropriately. We suggest that the PHA-4 amino terminus is essential for PHA-4 function in vivo, possibly as a transactivation domain, and can compensate for loss of the carboxyl terminus. We also provide evidence for autoregulation by PHA-4.
authors.affiliation: Huntsman Cancer Institute and Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Kaltenbach
authors.forename: Dustin L
authors.initials: DL
authors.lastname: Updike
authors.forename: Susan E
authors.initials: SE
authors.lastname: Mango
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D004247:DNA / Q000737:chemistry; D006579:Heterozygote; D006720:Homozygote; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: D029742:Caenorhabditis elegans Proteins; C113277:Pha-4 protein, C elegans; D015534:Trans-Activators; D004247:DNA