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. 1991 Feb 11;19(3):573–578. doi: 10.1093/nar/19.3.573

Genomic organization of the retinoic acid receptor gamma gene.

J M Lehmann 1, B Hoffmann 1, M Pfahl 1
PMCID: PMC333650  PMID: 1849262

Abstract

The retinoic acid receptors (RAR) belong to the large family of ligand responsive gene regulatory proteins that includes receptors for steroid and thyroid hormones. These proteins contain two highly conserved domains, involved in determining their DNA and ligand binding activities. Three distinct RARs have been identified (RAR alpha, beta, and gamma) which are encoded by genes on separate chromosomes. Additional isoforms of the three receptors have been described that all differ in the N-terminal regions. To gain insight into the genomic organization and mechanisms of RAR isoform generation, we have analyzed the genomic structure of the RAR gamma gene. The major portion of the RAR gamma protein, including DNA and ligand binding domains, is encoded by seven exons that are identical for all RARg isoforms and are represented by a relatively small portion of the RAR gamma gene. The major portion of this gene encodes separate N-terminal exons for gamma 1 and gamma 2 isoforms and several exons for gamma 1 untranslated regions. We show that RAR gamma 2 transcription is regulated by its own promoter. In comparison with the steroid receptor subfamily, various splice sites of RAR gamma occur at altered positions, suggesting that the RAR subfamily has diverged early during evolution.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benbrook D., Lernhardt E., Pfahl M. A new retinoic acid receptor identified from a hepatocellular carcinoma. Nature. 1988 Jun 16;333(6174):669–672. doi: 10.1038/333669a0. [DOI] [PubMed] [Google Scholar]
  2. Benbrook D., Pfahl M. A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library. Science. 1987 Nov 6;238(4828):788–791. doi: 10.1126/science.3672126. [DOI] [PubMed] [Google Scholar]
  3. Brand N., Petkovich M., Krust A., Chambon P., de Thé H., Marchio A., Tiollais P., Dejean A. Identification of a second human retinoic acid receptor. Nature. 1988 Apr 28;332(6167):850–853. doi: 10.1038/332850a0. [DOI] [PubMed] [Google Scholar]
  4. Chen C. A., Okayama H. Calcium phosphate-mediated gene transfer: a highly efficient transfection system for stably transforming cells with plasmid DNA. Biotechniques. 1988 Jul-Aug;6(7):632–638. [PubMed] [Google Scholar]
  5. Dollé P., Ruberte E., Kastner P., Petkovich M., Stoner C. M., Gudas L. J., Chambon P. Differential expression of genes encoding alpha, beta and gamma retinoic acid receptors and CRABP in the developing limbs of the mouse. Nature. 1989 Dec 7;342(6250):702–705. doi: 10.1038/342702a0. [DOI] [PubMed] [Google Scholar]
  6. Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. doi: 10.1126/science.3283939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fawell S. E., Lees J. A., White R., Parker M. G. Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor. Cell. 1990 Mar 23;60(6):953–962. doi: 10.1016/0092-8674(90)90343-d. [DOI] [PubMed] [Google Scholar]
  8. Forman B. M., Samuels H. H. Dimerization among nuclear hormone receptors. New Biol. 1990 Jul;2(7):587–594. [PubMed] [Google Scholar]
  9. Forrest D., Sjöberg M., Vennström B. Contrasting developmental and tissue-specific expression of alpha and beta thyroid hormone receptor genes. EMBO J. 1990 May;9(5):1519–1528. doi: 10.1002/j.1460-2075.1990.tb08270.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Giguere V., Ong E. S., Segui P., Evans R. M. Identification of a receptor for the morphogen retinoic acid. Nature. 1987 Dec 17;330(6149):624–629. doi: 10.1038/330624a0. [DOI] [PubMed] [Google Scholar]
  11. Giguère V., Shago M., Zirngibl R., Tate P., Rossant J., Varmuza S. Identification of a novel isoform of the retinoic acid receptor gamma expressed in the mouse embryo. Mol Cell Biol. 1990 May;10(5):2335–2340. doi: 10.1128/mcb.10.5.2335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Glass C. K., Holloway J. M., Devary O. V., Rosenfeld M. G. The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence motif in thyroid hormone and estrogen response elements. Cell. 1988 Jul 29;54(3):313–323. doi: 10.1016/0092-8674(88)90194-8. [DOI] [PubMed] [Google Scholar]
  13. Graupner G., Wills K. N., Tzukerman M., Zhang X. K., Pfahl M. Dual regulatory role for thyroid-hormone receptors allows control of retinoic-acid receptor activity. Nature. 1989 Aug 24;340(6235):653–656. doi: 10.1038/340653a0. [DOI] [PubMed] [Google Scholar]
  14. Green S., Chambon P. Nuclear receptors enhance our understanding of transcription regulation. Trends Genet. 1988 Nov;4(11):309–314. doi: 10.1016/0168-9525(88)90108-4. [DOI] [PubMed] [Google Scholar]
  15. Gronemeyer H., Turcotte B., Quirin-Stricker C., Bocquel M. T., Meyer M. E., Krozowski Z., Jeltsch J. M., Lerouge T., Garnier J. M., Chambon P. The chicken progesterone receptor: sequence, expression and functional analysis. EMBO J. 1987 Dec 20;6(13):3985–3994. doi: 10.1002/j.1460-2075.1987.tb02741.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hodin R. A., Lazar M. A., Wintman B. I., Darling D. S., Koenig R. J., Larsen P. R., Moore D. D., Chin W. W. Identification of a thyroid hormone receptor that is pituitary-specific. Science. 1989 Apr 7;244(4900):76–79. doi: 10.1126/science.2539642. [DOI] [PubMed] [Google Scholar]
  17. Hollenberg S. M., Giguere V., Segui P., Evans R. M. Colocalization of DNA-binding and transcriptional activation functions in the human glucocorticoid receptor. Cell. 1987 Apr 10;49(1):39–46. doi: 10.1016/0092-8674(87)90753-7. [DOI] [PubMed] [Google Scholar]
  18. Jeltsch J. M., Turcotte B., Garnier J. M., Lerouge T., Krozowski Z., Gronemeyer H., Chambon P. Characterization of multiple mRNAs originating from the chicken progesterone receptor gene. Evidence for a specific transcript encoding form A. J Biol Chem. 1990 Mar 5;265(7):3967–3974. [PubMed] [Google Scholar]
  19. Kastner P., Krust A., Mendelsohn C., Garnier J. M., Zelent A., Leroy P., Staub A., Chambon P. Murine isoforms of retinoic acid receptor gamma with specific patterns of expression. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2700–2704. doi: 10.1073/pnas.87.7.2700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Krust A., Kastner P., Petkovich M., Zelent A., Chambon P. A third human retinoic acid receptor, hRAR-gamma. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5310–5314. doi: 10.1073/pnas.86.14.5310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lubahn D. B., Brown T. R., Simental J. A., Higgs H. N., Migeon C. J., Wilson E. M., French F. S. Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9534–9538. doi: 10.1073/pnas.86.23.9534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mader S., Kumar V., de Verneuil H., Chambon P. Three amino acids of the oestrogen receptor are essential to its ability to distinguish an oestrogen from a glucocorticoid-responsive element. Nature. 1989 Mar 16;338(6212):271–274. doi: 10.1038/338271a0. [DOI] [PubMed] [Google Scholar]
  23. Miesfeld R., Godowski P. J., Maler B. A., Yamamoto K. R. Glucocorticoid receptor mutants that define a small region sufficient for enhancer activation. Science. 1987 Apr 24;236(4800):423–427. doi: 10.1126/science.3563519. [DOI] [PubMed] [Google Scholar]
  24. Millán J. L. Molecular cloning and sequence analysis of human placental alkaline phosphatase. J Biol Chem. 1986 Mar 5;261(7):3112–3115. [PubMed] [Google Scholar]
  25. Petkovich M., Brand N. J., Krust A., Chambon P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature. 1987 Dec 3;330(6147):444–450. doi: 10.1038/330444a0. [DOI] [PubMed] [Google Scholar]
  26. Pfahl M., Tzukerman M., Zhang X. K., Lehmann J. M., Hermann T., Wills K. N., Graupner G. Nuclear retinoic acid receptors: cloning, analysis, and function. Methods Enzymol. 1990;189:256–270. doi: 10.1016/0076-6879(90)89297-u. [DOI] [PubMed] [Google Scholar]
  27. Ponglikitmongkol M., Green S., Chambon P. Genomic organization of the human oestrogen receptor gene. EMBO J. 1988 Nov;7(11):3385–3388. doi: 10.1002/j.1460-2075.1988.tb03211.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ruberte E., Dolle P., Krust A., Zelent A., Morriss-Kay G., Chambon P. Specific spatial and temporal distribution of retinoic acid receptor gamma transcripts during mouse embryogenesis. Development. 1990 Feb;108(2):213–222. doi: 10.1242/dev.108.2.213. [DOI] [PubMed] [Google Scholar]
  29. Ryseck R. P., Macdonald-Bravo H., Mattéi M. G., Ruppert S., Bravo R. Structure, mapping and expression of a growth factor inducible gene encoding a putative nuclear hormonal binding receptor. EMBO J. 1989 Nov;8(11):3327–3335. doi: 10.1002/j.1460-2075.1989.tb08494.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  32. Thaller C., Eichele G. Identification and spatial distribution of retinoids in the developing chick limb bud. Nature. 1987 Jun 18;327(6123):625–628. doi: 10.1038/327625a0. [DOI] [PubMed] [Google Scholar]
  33. Thaller C., Eichele G. Isolation of 3,4-didehydroretinoic acid, a novel morphogenetic signal in the chick wing bud. Nature. 1990 Jun 28;345(6278):815–819. doi: 10.1038/345815a0. [DOI] [PubMed] [Google Scholar]
  34. Umesono K., Evans R. M. Determinants of target gene specificity for steroid/thyroid hormone receptors. Cell. 1989 Jun 30;57(7):1139–1146. doi: 10.1016/0092-8674(89)90051-2. [DOI] [PubMed] [Google Scholar]
  35. Zahraoui A., Cuny G. Nucleotide sequence of the chicken proto-oncogene c-erbA corresponding to domain 1 of v-erbA. Eur J Biochem. 1987 Jul 1;166(1):63–69. doi: 10.1111/j.1432-1033.1987.tb13484.x. [DOI] [PubMed] [Google Scholar]

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