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http://purl.uniprot.org/citations/18179707http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18179707http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18179707http://www.w3.org/2000/01/rdf-schema#comment"

Background

The nuclear receptors of the NR2E class play important roles in pattern formation and nervous system development. Based on a phylogenetic analysis of DNA-binding domains, we define two conserved groups of orthologous NR2E genes: the NR2E1 subclass, which includes C. elegans nhr-67, Drosophila tailless and dissatisfaction, and vertebrate Tlx (NR2E2, NR2E4, NR2E1), and the NR2E3 subclass, which includes C. elegans fax-1 and vertebrate PNR (NR2E5, NR2E3). PNR and Tll nuclear receptors have been shown to bind the hexamer half-site AAGTCA, instead of the hexamer AGGTCA recognized by most other nuclear receptors, suggesting unique DNA-binding properties for NR2E class members.

Results

We show that NR2E3 subclass member FAX-1, unlike NHR-67 and other NR2E1 subclass members, binds to hexamer half-sites with relaxed specificity: it will bind hexamers with the sequence ANGTCA, although it prefers a purine to a pyrimidine at the second position. We use site-directed mutagenesis to demonstrate that the difference between FAX-1 and NHR-67 binding preference is partially mediated by a conserved subclass-specific asparagine or aspartate residue at position 19 of the DNA-binding domain. This amino acid position is part of the "P box" that plays a critical role in defining binding site specificity and has been shown to make hydrogen-bond contacts to the second position of the hexamer in co-crystal structures for other nuclear receptors. The relaxed specificity allows FAX-1 to bind a much larger repertoire of half-sites than NHR-67. While NR2E1 class proteins bind both monomeric and dimeric sites, the NR2E3 class proteins bind only dimeric sites. The presence of a single strong site adjacent to a very weak site allows dimeric FAX-1 binding, further increasing the number of dimeric binding sites to which FAX-1 may bind in vivo.

Conclusion

These findings identify subclass-specific DNA-binding specificities and dimerization properties for the NR2E1 and NR2E3 subclasses. For the NR2E1 protein NHR-67, Asp-19 permits binding to AAGTCA half-sites, while Asn-19 permits binding to AGGTCA half-sites. The apparent conservation of DNA-binding properties between vertebrate and nematode NR2E receptors allows for the possibility of evolutionarily-conserved regulatory patterns."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.org/dc/terms/identifier"doi:10.1186/1471-2199-9-2"xsd:string
http://purl.uniprot.org/citations/18179707http://purl.org/dc/terms/identifier"doi:10.1186/1471-2199-9-2"xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"Reinert K."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"Reinert K."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"Smith E.L."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"Smith E.L."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"Clever S."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"Clever S."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"Cronin M."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"Cronin M."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"DeMeo S.D."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"DeMeo S.D."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"Lombel R.M."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"Lombel R.M."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"Snowflack D.R."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"Snowflack D.R."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"Wightman B."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/author"Wightman B."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/name"BMC Mol. Biol."xsd:string
http://purl.uniprot.org/citations/18179707http://purl.uniprot.org/core/name"BMC Mol. Biol."xsd:string
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