Nuclear Receptor Genes

Abstract

Nuclear receptors are ligand‐dependant transcription factors that can directly regulate target genes in response to hormonal ligands, such as steroids, retinoic acid or thyroid hormones. They form a superfamily of genes that have a complex organization with most often alternative promoters, alternative splicing and autoregulation mechanisms. These genes are dispersed in metazoan genomes and their number varies widely from one genome to another (from 21 in Drosophila to about 270 in nematodes).

Keywords: genomes; gene regulation; human; Drosophila; nematode

Figure 1.

Structure of a bona fide NR, showing the various domains and their main functions. From the N‐terminus to the C‐terminus the domains are as follows: the A/B domain, which is implicated in transactivation; the DNA‐binding domain (DBD) or C domain, which is also important for dimerization; the variable hinge or D domain; the ligand‐binding domain (LBD) or E domain, which is implicated in ligand binding, transcriptional regulation and dimerization; and the F domain, which is present in some but not all NRs. The T/A box, which is important for DNA binding, and the AF2‐AD region, which is required for ligand‐dependant transcriptional activation, are also shown. The two small arrows indicate the position of two introns that are conserved in most NRs.

Figure 2.

Organization of the 5′ region of the mouse RARB gene and the principal isoforms expressed. Exons (E1–E5) are indicated by boxes. Dark and light shading represents the translated sequence and the 5′ untranslated region respectively. The initiator codon (AUG or CUG) used for each isoform is indicated, as well as the two promoters that control expression of the RARB gene: P1, which is constitutive; and P2, which is regulated by retinoic acid. The various isoforms differ only in the N‐terminal part of the A/B domain, which is implicated in transactivation. Figure is based on data from Zelent et al..

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References

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Further Reading

Conneely OM, Mulac‐Jericevic B, Lydon JP and De Mayo FJ (2001) Reproductive functions of the progesterone receptor isoforms: lessons from knock‐out mice. Molecular and Cellular Endocrinology 179: 97–103.

Escriva H, Delaunay F and Laudet V (2000) Ligand binding and nuclear receptor evolution. BioEssays 22: 717–727.

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Kliewer SA, Lehmann JM and Willson TM (1999) Orphan nuclear receptors: shifting endocrinology into reverse. Science 284: 757–760.

Laudet V and Gronemeyer H (2002) The Nuclear Receptor Factsbook London, UK: Academic Press.

Mangelsdorf DJ, Thummel C, Beato M, et al. (1995) The nuclear receptor superfamily: the second decade. Cell 83: 835–839.

McKenna NJ and O'Malley BW (2002) Combinatorial control of gene expression by nuclear receptors and coregulators. Cell 108: 465–474.

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Web Links

Nuclear Receptor Nomenclature Committee http://www.ens‐lyon.fr/LBMC/laudet/NucRec/nomenclature.html

NCBI BLAST http://www.ncbi.nlm.nih.gov/BLAST/

Peroxisome proliferative activated receptor, alpha (PPARA); LocusID: 5465. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5465

Progesterone receptor (PGR); LocusID: 5421. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5421

Retinoic acid receptor, alpha (RARA); LocusID: 5914. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5914

Retinoid X receptor, alpha (RXRA); LocusID: 6256. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=6256

Thyroid hormone receptor, alpha (THRA); LocusID: 7067. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=7067

Peroxisome proliferative activated receptor, alpha (PPARA); MIM number: 170998. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?170998

Progesterone receptor (PGR); MIM number: 607311. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?607311

Retinoic acid receptor, alpha (RARA); MIM number: 180240. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?180240

Retinoid X receptor, alpha (RXRA); MIM number: 180245. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?180245

Thyroid hormone receptor, alpha (THRA); MIM number: 190120. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?190120

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How to Cite close
Laudet, Vincent(Jan 2006) Nuclear Receptor Genes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0006154]