Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Feb 15;89(4):1448–1452. doi: 10.1073/pnas.89.4.1448

Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling.

S A Kliewer 1, K Umesono 1, R A Heyman 1, D J Mangelsdorf 1, J A Dyck 1, R M Evans 1
PMCID: PMC48468  PMID: 1311101

Abstract

We have recently described the properties of direct repeats (DRs) of the half-site AGGTCA as hormone response elements (HREs). According to our results, spacing the half sites by 3, 4, or 5 nucleotides determines specificity of response for vitamin D3, thyroid hormone, and retinoic acid receptors, respectively. This so-called 3-4-5 rule led to the prediction that remaining spacing options of 0, 1, and 2 might serve as targets for other nuclear receptors. A concurrent prediction is that receptors recognizing common sites might display more complex or combinatorial interactions. In exploring these predictions, we discovered that both the retinoid X receptor (RXR) and COUP-TF bind preferentially to a DR-1 motif. In vivo, RXR and COUP-TF display antagonistic action such that RXR-mediated activation is fully repressed by COUP-TF. In vitro studies reveal that COUP-TF and RXR form heterodimers on DR-1. Thus, these results support a general proposal in which the half-site spacing preferences may be used as a means to decipher potentially complex and interactive regulatory circuits.

Full text

PDF
1448

Images in this article

1449Image
on p.1449
1450Image
on p.1450
1450Image
on p.1450
1450Image
on p.1450
1450Image
on p.1450
1451Image
on p.1451
1451Image
on p.1451
1451Image
on p.1451
1451Image
on p.1451

Selected References

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

  1. 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]
  2. Gibbs J. B. Ras C-terminal processing enzymes--new drug targets? Cell. 1991 Apr 5;65(1):1–4. doi: 10.1016/0092-8674(91)90352-y. [DOI] [PubMed] [Google Scholar]
  3. Glass C. K., Lipkin S. M., Devary O. V., Rosenfeld M. G. Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer. Cell. 1989 Nov 17;59(4):697–708. doi: 10.1016/0092-8674(89)90016-0. [DOI] [PubMed] [Google Scholar]
  4. Haddad I. A., Ordovas J. M., Fitzpatrick T., Karathanasis S. K. Linkage, evolution, and expression of the rat apolipoprotein A-I, C-III, and A-IV genes. J Biol Chem. 1986 Oct 5;261(28):13268–13277. [PubMed] [Google Scholar]
  5. Hijikata M., Wen J. K., Osumi T., Hashimoto T. Rat peroxisomal 3-ketoacyl-CoA thiolase gene. Occurrence of two closely related but differentially regulated genes. J Biol Chem. 1990 Mar 15;265(8):4600–4606. [PubMed] [Google Scholar]
  6. Hwung Y. P., Crowe D. T., Wang L. H., Tsai S. Y., Tsai M. J. The COUP transcription factor binds to an upstream promoter element of the rat insulin II gene. Mol Cell Biol. 1988 May;8(5):2070–2077. doi: 10.1128/mcb.8.5.2070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ladias J. A., Karathanasis S. K. Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily. Science. 1991 Feb 1;251(4993):561–565. doi: 10.1126/science.1899293. [DOI] [PubMed] [Google Scholar]
  8. Lucas P. C., O'Brien R. M., Mitchell J. A., Davis C. M., Imai E., Forman B. M., Samuels H. H., Granner D. K. A retinoic acid response element is part of a pleiotropic domain in the phosphoenolpyruvate carboxykinase gene. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2184–2188. doi: 10.1073/pnas.88.6.2184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mangelsdorf D. J., Ong E. S., Dyck J. A., Evans R. M. Nuclear receptor that identifies a novel retinoic acid response pathway. Nature. 1990 May 17;345(6272):224–229. doi: 10.1038/345224a0. [DOI] [PubMed] [Google Scholar]
  10. Mangelsdorf D. J., Umesono K., Kliewer S. A., Borgmeyer U., Ong E. S., Evans R. M. A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR. Cell. 1991 Aug 9;66(3):555–561. doi: 10.1016/0092-8674(81)90018-0. [DOI] [PubMed] [Google Scholar]
  11. Miyajima N., Kadowaki Y., Fukushige S., Shimizu S., Semba K., Yamanashi Y., Matsubara K., Toyoshima K., Yamamoto T. Identification of two novel members of erbA superfamily by molecular cloning: the gene products of the two are highly related to each other. Nucleic Acids Res. 1988 Dec 9;16(23):11057–11074. doi: 10.1093/nar/16.23.11057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Murakami T., Nishiyori A., Takiguchi M., Mori M. Promoter and 11-kilobase upstream enhancer elements responsible for hepatoma cell-specific expression of the rat ornithine transcarbamylase gene. Mol Cell Biol. 1990 Mar;10(3):1180–1191. doi: 10.1128/mcb.10.3.1180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. O'Malley B. The steroid receptor superfamily: more excitement predicted for the future. Mol Endocrinol. 1990 Mar;4(3):363–369. doi: 10.1210/mend-4-3-363. [DOI] [PubMed] [Google Scholar]
  14. Osumi T., Ishii N., Miyazawa S., Hashimoto T. Isolation and structural characterization of the rat acyl-CoA oxidase gene. J Biol Chem. 1987 Jun 15;262(17):8138–8143. [PubMed] [Google Scholar]
  15. Power R. F., Lydon J. P., Conneely O. M., O'Malley B. W. Dopamine activation of an orphan of the steroid receptor superfamily. Science. 1991 Jun 14;252(5012):1546–1548. doi: 10.1126/science.2047861. [DOI] [PubMed] [Google Scholar]
  16. Rivier J., Rivier C., Vale W. Synthetic competitive antagonists of corticotropin-releasing factor: effect on ACTH secretion in the rat. Science. 1984 May 25;224(4651):889–891. doi: 10.1126/science.6326264. [DOI] [PubMed] [Google Scholar]
  17. Sagami I., Tsai S. Y., Wang H., Tsai M. J., O'Malley B. W. Identification of two factors required for transcription of the ovalbumin gene. Mol Cell Biol. 1986 Dec;6(12):4259–4267. doi: 10.1128/mcb.6.12.4259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sastry K. N., Seedorf U., Karathanasis S. K. Different cis-acting DNA elements control expression of the human apolipoprotein AI gene in different cell types. Mol Cell Biol. 1988 Feb;8(2):605–614. doi: 10.1128/mcb.8.2.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sladek F. M., Zhong W. M., Lai E., Darnell J. E., Jr Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev. 1990 Dec;4(12B):2353–2365. doi: 10.1101/gad.4.12b.2353. [DOI] [PubMed] [Google Scholar]
  20. Sucov H. M., Murakami K. K., Evans R. M. Characterization of an autoregulated response element in the mouse retinoic acid receptor type beta gene. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5392–5396. doi: 10.1073/pnas.87.14.5392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Vaughan J. M., Rivier J., Corrigan A. Z., McClintock R., Campen C. A., Jolley D., Voglmayr J. K., Bardin C. W., Rivier C., Vale W. Detection and purification of inhibin using antisera generated against synthetic peptide fragments. Methods Enzymol. 1989;168:588–617. doi: 10.1016/0076-6879(89)68044-5. [DOI] [PubMed] [Google Scholar]
  22. Wang L. H., Tsai S. Y., Cook R. G., Beattie W. G., Tsai M. J., O'Malley B. W. COUP transcription factor is a member of the steroid receptor superfamily. Nature. 1989 Jul 13;340(6229):163–166. doi: 10.1038/340163a0. [DOI] [PubMed] [Google Scholar]
  23. Wijnholds J., Muller E., Ab G. Oestrogen facilitates the binding of ubiquitous and liver-enriched nuclear proteins to the apoVLDL II promoter in vivo. Nucleic Acids Res. 1991 Jan 11;19(1):33–41. doi: 10.1093/nar/19.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. de Thé H., Vivanco-Ruiz M. M., Tiollais P., Stunnenberg H., Dejean A. Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene. Nature. 1990 Jan 11;343(6254):177–180. doi: 10.1038/343177a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES