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A functional NR4A nuclear receptor DNA‐binding domain is required for organ development in Caenorhabditis elegans
Author(s) -
Heard Melissa,
Maina Claude V.,
Morehead Benjamin E.,
Hoener Marius C.,
Nguyen Tri Q.,
Williams Christopher C.,
Rowan Brian G.,
Gissendanner Chris R.
Publication year - 2010
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20646
Subject(s) - nuclear receptor , biology , microbiology and biotechnology , caenorhabditis elegans , dna binding domain , nuclear dna , cell fate determination , receptor , transcription factor , genetics , gene , mitochondrial dna
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. genesis 48:485–491, 2010. © 2010 Wiley‐Liss, Inc.