A functional NR4A nuclear receptor DNA-binding domain is required for organ development in Caenorhabditis elegans.

NR4A nuclear receptors are a diverse group of orphan nuclear receptors with critical roles in regulating cell proliferation and cell differentiation. The ortholog of the NR4A nuclear receptor in Caenorhabditis elegans, NHR-6, also has a role in cell proliferation and cell differentiation during organogenesis of the spermatheca. Here we show that NHR-6 is able to bind the canonical NR4A monomer response element and can transactivate from this site in mammalian HEK293 cells. Using a functional GFP-tagged NHR-6 fusion, we also demonstrate that NHR-6 is nuclear localized during development of the spermatheca. Mutation of the DNA-binding domain of NHR-6 abolishes its activity in genetic rescue assays, demonstrating a requirement for the DNA-binding domain. This study represents the first genetic demonstration of an in vivo requirement for an NR4A nuclear receptor DNA-binding domain in a whole organism.

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