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Nucleic Acids Res. 1991 February 11; 19(3): 573–578.
PMCID: PMC333650

Genomic organization of the retinoic acid receptor gamma gene.

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

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  • 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. [PubMed]
  • Kastner P, Krust A, Mendelsohn C, Garnier JM, 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. [PubMed]
  • Hodin RA, Lazar MA, Wintman BI, Darling DS, Koenig RJ, Larsen PR, Moore DD, Chin WW. Identification of a thyroid hormone receptor that is pituitary-specific. Science. 1989 Apr 7;244(4900):76–79. [PubMed]
  • 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. [PubMed]
  • 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. [PubMed]
  • Millán JL. Molecular cloning and sequence analysis of human placental alkaline phosphatase. J Biol Chem. 1986 Mar 5;261(7):3112–3115. [PubMed]
  • Pfahl M, Tzukerman M, Zhang XK, Lehmann JM, Hermann T, Wills KN, Graupner G. Nuclear retinoic acid receptors: cloning, analysis, and function. Methods Enzymol. 1990;189:256–270. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PubMed]
  • Chen CA, 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]
  • 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. [PubMed]
  • Graupner G, Wills KN, Tzukerman M, Zhang XK, Pfahl M. Dual regulatory role for thyroid-hormone receptors allows control of retinoic-acid receptor activity. Nature. 1989 Aug 24;340(6235):653–656. [PubMed]
  • Jeltsch JM, Turcotte B, Garnier JM, 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]
  • Lubahn DB, Brown TR, Simental JA, Higgs HN, Migeon CJ, Wilson EM, French FS. 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. [PubMed]
  • Ponglikitmongkol M, Green S, Chambon P. Genomic organization of the human oestrogen receptor gene. EMBO J. 1988 Nov;7(11):3385–3388. [PubMed]
  • Gronemeyer H, Turcotte B, Quirin-Stricker C, Bocquel MT, Meyer ME, Krozowski Z, Jeltsch JM, Lerouge T, Garnier JM, Chambon P. The chicken progesterone receptor: sequence, expression and functional analysis. EMBO J. 1987 Dec 20;6(13):3985–3994. [PubMed]
  • 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. [PubMed]
  • Ryseck RP, Macdonald-Bravo H, Mattéi MG, 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. [PubMed]
  • 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. [PubMed]
  • Umesono K, Evans RM. Determinants of target gene specificity for steroid/thyroid hormone receptors. Cell. 1989 Jun 30;57(7):1139–1146. [PubMed]
  • Glass CK, Holloway JM, Devary OV, Rosenfeld MG. 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. [PubMed]
  • Miesfeld R, Godowski PJ, Maler BA, Yamamoto KR. Glucocorticoid receptor mutants that define a small region sufficient for enhancer activation. Science. 1987 Apr 24;236(4800):423–427. [PubMed]
  • Hollenberg SM, Giguere V, Segui P, Evans RM. Colocalization of DNA-binding and transcriptional activation functions in the human glucocorticoid receptor. Cell. 1987 Apr 10;49(1):39–46. [PubMed]
  • Thaller C, Eichele G. Identification and spatial distribution of retinoids in the developing chick limb bud. Nature. 1987 Jun 18;327(6123):625–628. [PubMed]
  • 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. [PubMed]
  • Giguere V, Ong ES, Segui P, Evans RM. Identification of a receptor for the morphogen retinoic acid. Nature. 1987 Dec 17;330(6149):624–629. [PubMed]
  • Petkovich M, Brand NJ, 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. [PubMed]
  • Benbrook D, Lernhardt E, Pfahl M. A new retinoic acid receptor identified from a hepatocellular carcinoma. Nature. 1988 Jun 16;333(6174):669–672. [PubMed]
  • 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. [PubMed]
  • Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. [PubMed]
  • Green S, Chambon P. Nuclear receptors enhance our understanding of transcription regulation. Trends Genet. 1988 Nov;4(11):309–314. [PubMed]
  • Fawell SE, Lees JA, White R, Parker MG. Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor. Cell. 1990 Mar 23;60(6):953–962. [PubMed]
  • Forman BM, Samuels HH. Dimerization among nuclear hormone receptors. New Biol. 1990 Jul;2(7):587–594. [PubMed]
  • 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. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Dollé P, Ruberte E, Kastner P, Petkovich M, Stoner CM, Gudas LJ, 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. [PubMed]

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