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.
Heard
Melissa
M
Maina
Claude V
CV
Morehead
Benjamin E
BE
Hoener
Marius C
MC
Nguyen
Tri Q
TQ
Williams
Christopher C
CC
Rowan
Brian G
BG
Gissendanner
Chris R
CR
D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites / Q000235:genetics / Q000502:physiology; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005816:Genetic Complementation Test; D006066:Gonads / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D009154:Mutation; D038081:Organogenesis / Q000235:genetics*; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D014162:Transfection
D029742:Caenorhabditis elegans Proteins; C526782:Nhr-6 protein, C elegans; D018160:Receptors, Cytoplasmic and Nuclear; D049452:Green Fluorescent Proteins; D004247:DNA