Work

Contribution of the amino and carboxyl termini for PHA‐4/FoxA function in Caenorhabditis elegans

Year: 2005

Type: article

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.

Source: Developmental Dynamics

DOI: 10.1002/dvdy.20550

Authors: Linda S. Kaltenbach, Dustin L. Updike, Susan E. Mango

Institutions: University of Utah, Huntsman Cancer Institute

Language: English

Topic: Developmental Biology and Gene Regulation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: bronze

Funders: National Institute of Nursing Research, National Institute of General Medical Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development