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. 1994 Jan;14(1):360–372. doi: 10.1128/mcb.14.1.360

Dominant negative retinoid X receptor beta inhibits retinoic acid-responsive gene regulation in embryonal carcinoma cells.

S Minucci 1, D J Zand 1, A Dey 1, M S Marks 1, T Nagata 1, J F Grippo 1, K Ozato 1
PMCID: PMC358385  PMID: 8264603

Abstract

Retinoid X receptors (RXRs) heterodimerize with multiple nuclear hormone receptors and are thought to exert pleiotropic functions. To address the role of RXRs in retinoic acid- (RA) mediated gene regulation, we designed a dominant negative RXR beta. This mutated receptor, termed DBD-, lacked the DNA binding domain but retained the ability to dimerize with partner receptors, resulting in formation of nonfunctional dimers. DBD- was transfected into P19 murine embryonal carcinoma (EC) cells, in which reporters containing the RA-responsive elements (RAREs) were activated by RA through the activity of endogenous RXR-RA receptor (RAR) heterodimers. We found that DBD- had a dominant negative activity on the RARE reporter activity in these cells. P19 clones stably expressing DBD- were established; these clones also failed to activate RARE-driven reporters in response to RA. Further, these cells were defective in RA-induced mRNA expression of Hox-1.3 and RAR beta, as well as in RA-induced down-regulation of Oct3 mRNA. Gel mobility shift assays demonstrated that RA treatment of control P19 cells induces RARE-binding activity, of which RXR beta is a major component. However, the RA-induced binding activity was greatly reduced in cells expressing DBD-. By genomic footprinting, we show that RA treatment induces in vivo occupancy of the RARE in the endogenous RAR beta gene in control P19 cells but that this occupancy is not observed with the DBD- cells. These data provide evidence that the dominant negative activity of DBD- is caused by the lack of receptor binding to target DNA. Finally, we show that in F9 EC cells expression of DBD- leads to inhibition of the growth arrest that accompanies RA-induced differentiation. Taken together, these results demonstrate that RXR beta and partner receptors play a central role in RA-mediated gene regulation and in the control of growth and differentiation in EC cells.

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Selected References

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  1. Allenby G., Bocquel M. T., Saunders M., Kazmer S., Speck J., Rosenberger M., Lovey A., Kastner P., Grippo J. F., Chambon P. Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):30–34. doi: 10.1073/pnas.90.1.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alonso A., Breuer B., Steuer B., Fischer J. The F9-EC cell line as a model for the analysis of differentiation. Int J Dev Biol. 1991 Dec;35(4):389–397. [PubMed] [Google Scholar]
  3. Barettino D., Bugge T. H., Bartunek P., Vivanco Ruiz M. D., Sonntag-Buck V., Beug H., Zenke M., Stunnenberg H. G. Unliganded T3R, but not its oncogenic variant, v-erbA, suppresses RAR-dependent transactivation by titrating out RXR. EMBO J. 1993 Apr;12(4):1343–1354. doi: 10.1002/j.1460-2075.1993.tb05779.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beato M. Gene regulation by steroid hormones. Cell. 1989 Feb 10;56(3):335–344. doi: 10.1016/0092-8674(89)90237-7. [DOI] [PubMed] [Google Scholar]
  5. Bigler J., Hokanson W., Eisenman R. N. Thyroid hormone receptor transcriptional activity is potentially autoregulated by truncated forms of the receptor. Mol Cell Biol. 1992 May;12(5):2406–2417. doi: 10.1128/mcb.12.5.2406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bugge T. H., Pohl J., Lonnoy O., Stunnenberg H. G. RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors. EMBO J. 1992 Apr;11(4):1409–1418. doi: 10.1002/j.1460-2075.1992.tb05186.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  9. Danielsen M., Hinck L., Ringold G. M. Two amino acids within the knuckle of the first zinc finger specify DNA response element activation by the glucocorticoid receptor. Cell. 1989 Jun 30;57(7):1131–1138. doi: 10.1016/0092-8674(89)90050-0. [DOI] [PubMed] [Google Scholar]
  10. Dey A., Thornton A. M., Lonergan M., Weissman S. M., Chamberlain J. W., Ozato K. Occupancy of upstream regulatory sites in vivo coincides with major histocompatibility complex class I gene expression in mouse tissues. Mol Cell Biol. 1992 Aug;12(8):3590–3599. doi: 10.1128/mcb.12.8.3590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Durand B., Saunders M., Leroy P., Leid M., Chambon P. All-trans and 9-cis retinoic acid induction of CRABPII transcription is mediated by RAR-RXR heterodimers bound to DR1 and DR2 repeated motifs. Cell. 1992 Oct 2;71(1):73–85. doi: 10.1016/0092-8674(92)90267-g. [DOI] [PubMed] [Google Scholar]
  12. Espeseth A. S., Murphy S. P., Linney E. Retinoic acid receptor expression vector inhibits differentiation of F9 embryonal carcinoma cells. Genes Dev. 1989 Nov;3(11):1647–1656. doi: 10.1101/gad.3.11.1647. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Flanagan J. R., Becker K. G., Ennist D. L., Gleason S. L., Driggers P. H., Levi B. Z., Appella E., Ozato K. Cloning of a negative transcription factor that binds to the upstream conserved region of Moloney murine leukemia virus. Mol Cell Biol. 1992 Jan;12(1):38–44. doi: 10.1128/mcb.12.1.38. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Forman B. M., Samuels H. H. Interactions among a subfamily of nuclear hormone receptors: the regulatory zipper model. Mol Endocrinol. 1990 Sep;4(9):1293–1301. doi: 10.1210/mend-4-9-1293. [DOI] [PubMed] [Google Scholar]
  16. Forman B. M., Samuels H. H. pEXPRESS: a family of expression vectors containing a single transcription unit active in prokaryotes, eukaryotes and in vitro. Gene. 1991 Aug 30;105(1):9–15. doi: 10.1016/0378-1119(91)90507-8. [DOI] [PubMed] [Google Scholar]
  17. Forman B. M., Yang C. R., Au M., Casanova J., Ghysdael J., Samuels H. H. A domain containing leucine-zipper-like motifs mediate novel in vivo interactions between the thyroid hormone and retinoic acid receptors. Mol Endocrinol. 1989 Oct;3(10):1610–1626. doi: 10.1210/mend-3-10-1610. [DOI] [PubMed] [Google Scholar]
  18. Garrity P. A., Wold B. J. Effects of different DNA polymerases in ligation-mediated PCR: enhanced genomic sequencing and in vivo footprinting. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1021–1025. doi: 10.1073/pnas.89.3.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Gill G., Ptashne M. Negative effect of the transcriptional activator GAL4. Nature. 1988 Aug 25;334(6184):721–724. doi: 10.1038/334721a0. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Hamada K., Gleason S. L., Levi B. Z., Hirschfeld S., Appella E., Ozato K. H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8289–8293. doi: 10.1073/pnas.86.21.8289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Heyman R. A., Mangelsdorf D. J., Dyck J. A., Stein R. B., Eichele G., Evans R. M., Thaller C. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell. 1992 Jan 24;68(2):397–406. doi: 10.1016/0092-8674(92)90479-v. [DOI] [PubMed] [Google Scholar]
  24. Jones-Villeneuve E. M., McBurney M. W., Rogers K. A., Kalnins V. I. Retinoic acid induces embryonal carcinoma cells to differentiate into neurons and glial cells. J Cell Biol. 1982 Aug;94(2):253–262. doi: 10.1083/jcb.94.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jones-Villeneuve E. M., Rudnicki M. A., Harris J. F., McBurney M. W. Retinoic acid-induced neural differentiation of embryonal carcinoma cells. Mol Cell Biol. 1983 Dec;3(12):2271–2279. doi: 10.1128/mcb.3.12.2271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Jones N. Transcriptional regulation by dimerization: two sides to an incestuous relationship. Cell. 1990 Apr 6;61(1):9–11. doi: 10.1016/0092-8674(90)90207-u. [DOI] [PubMed] [Google Scholar]
  27. Jonk L. J., de Jonge M. E., Kruyt F. A., Mummery C. L., van der Saag P. T., Kruijer W. Aggregation and cell cycle dependent retinoic acid receptor mRNA expression in P19 embryonal carcinoma cells. Mech Dev. 1992 Feb;36(3):165–172. doi: 10.1016/0925-4773(92)90067-t. [DOI] [PubMed] [Google Scholar]
  28. Kitabayashi I., Kawakami Z., Chiu R., Ozawa K., Matsuoka T., Toyoshima S., Umesono K., Evans R. M., Gachelin G., Yokoyama K. Transcriptional regulation of the c-jun gene by retinoic acid and E1A during differentiation of F9 cells. EMBO J. 1992 Jan;11(1):167–175. doi: 10.1002/j.1460-2075.1992.tb05039.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kliewer S. A., Umesono K., Mangelsdorf D. J., Evans R. M. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature. 1992 Jan 30;355(6359):446–449. doi: 10.1038/355446a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kruyt F. A., van den Brink C. E., Defize L. H., Donath M. J., Kastner P., Kruijer W., Chambon P., van der Saag P. T. Transcriptional regulation of retinoic acid receptor beta in retinoic acid-sensitive and -resistant P19 embryocarcinoma cells. Mech Dev. 1991 Mar;33(3):171–178. doi: 10.1016/0925-4773(91)90025-2. [DOI] [PubMed] [Google Scholar]
  31. Langston A. W., Gudas L. J. Identification of a retinoic acid responsive enhancer 3' of the murine homeobox gene Hox-1.6. Mech Dev. 1992 Sep;38(3):217–227. doi: 10.1016/0925-4773(92)90055-o. [DOI] [PubMed] [Google Scholar]
  32. Lee M. S., Kliewer S. A., Provencal J., Wright P. E., Evans R. M. Structure of the retinoid X receptor alpha DNA binding domain: a helix required for homodimeric DNA binding. Science. 1993 May 21;260(5111):1117–1121. doi: 10.1126/science.8388124. [DOI] [PubMed] [Google Scholar]
  33. Leid M., Kastner P., Lyons R., Nakshatri H., Saunders M., Zacharewski T., Chen J. Y., Staub A., Garnier J. M., Mader S. Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell. 1992 Jan 24;68(2):377–395. doi: 10.1016/0092-8674(92)90478-u. [DOI] [PubMed] [Google Scholar]
  34. Leroy P., Krust A., Zelent A., Mendelsohn C., Garnier J. M., Kastner P., Dierich A., Chambon P. Multiple isoforms of the mouse retinoic acid receptor alpha are generated by alternative splicing and differential induction by retinoic acid. EMBO J. 1991 Jan;10(1):59–69. doi: 10.1002/j.1460-2075.1991.tb07921.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Leroy P., Nakshatri H., Chambon P. Mouse retinoic acid receptor alpha 2 isoform is transcribed from a promoter that contains a retinoic acid response element. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10138–10142. doi: 10.1073/pnas.88.22.10138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Levin A. A., Sturzenbecker L. J., Kazmer S., Bosakowski T., Huselton C., Allenby G., Speck J., Kratzeisen C., Rosenberger M., Lovey A. 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha. Nature. 1992 Jan 23;355(6358):359–361. doi: 10.1038/355359a0. [DOI] [PubMed] [Google Scholar]
  37. Linney E. Retinoic acid receptors: transcription factors modulating gene regulation, development, and differentiation. Curr Top Dev Biol. 1992;27:309–350. doi: 10.1016/s0070-2153(08)60538-4. [DOI] [PubMed] [Google Scholar]
  38. Mangelsdorf D. J., Borgmeyer U., Heyman R. A., Zhou J. Y., Ong E. S., Oro A. E., Kakizuka A., Evans R. M. Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev. 1992 Mar;6(3):329–344. doi: 10.1101/gad.6.3.329. [DOI] [PubMed] [Google Scholar]
  39. Marks M. S., Hallenbeck P. L., Nagata T., Segars J. H., Appella E., Nikodem V. M., Ozato K. H-2RIIBP (RXR beta) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes. EMBO J. 1992 Apr;11(4):1419–1435. doi: 10.1002/j.1460-2075.1992.tb05187.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Marks M. S., Levi B. Z., Segars J. H., Driggers P. H., Hirschfeld S., Nagata T., Appella E., Ozato K. H-2RIIBP expressed from a baculovirus vector binds to multiple hormone response elements. Mol Endocrinol. 1992 Feb;6(2):219–230. doi: 10.1210/mend.6.2.1569965. [DOI] [PubMed] [Google Scholar]
  41. Mendelsohn C., Ruberte E., Chambon P. Retinoid receptors in vertebrate limb development. Dev Biol. 1992 Jul;152(1):50–61. doi: 10.1016/0012-1606(92)90155-a. [DOI] [PubMed] [Google Scholar]
  42. Murphy S. P., Garbern J., Odenwald W. F., Lazzarini R. A., Linney E. Differential expression of the homeobox gene Hox-1.3 in F9 embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5587–5591. doi: 10.1073/pnas.85.15.5587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Nagata T., Segars J. H., Levi B. Z., Ozato K. Retinoic acid-dependent transactivation of major histocompatibility complex class I promoters by the nuclear hormone receptor H-2RIIBP in undifferentiated embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):937–941. doi: 10.1073/pnas.89.3.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Nagpal S., Zelent A., Chambon P. RAR-beta 4, a retinoic acid receptor isoform is generated from RAR-beta 2 by alternative splicing and usage of a CUG initiator codon. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2718–2722. doi: 10.1073/pnas.89.7.2718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Odenwald W. F., Taylor C. F., Palmer-Hill F. J., Friedrich V., Jr, Tani M., Lazzarini R. A. Expression of a homeo domain protein in noncontact-inhibited cultured cells and postmitotic neurons. Genes Dev. 1987 Jul;1(5):482–496. doi: 10.1101/gad.1.5.482. [DOI] [PubMed] [Google Scholar]
  46. Okamoto K., Okazawa H., Okuda A., Sakai M., Muramatsu M., Hamada H. A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells. Cell. 1990 Feb 9;60(3):461–472. doi: 10.1016/0092-8674(90)90597-8. [DOI] [PubMed] [Google Scholar]
  47. Okazawa H., Okamoto K., Ishino F., Ishino-Kaneko T., Takeda S., Toyoda Y., Muramatsu M., Hamada H. The oct3 gene, a gene for an embryonic transcription factor, is controlled by a retinoic acid repressible enhancer. EMBO J. 1991 Oct;10(10):2997–3005. doi: 10.1002/j.1460-2075.1991.tb07850.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. 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]
  49. Pratt M. A., Kralova J., McBurney M. W. A dominant negative mutation of the alpha retinoic acid receptor gene in a retinoic acid-nonresponsive embryonal carcinoma cell. Mol Cell Biol. 1990 Dec;10(12):6445–6453. doi: 10.1128/mcb.10.12.6445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Pöpperl H., Featherstone M. S. Identification of a retinoic acid response element upstream of the murine Hox-4.2 gene. Mol Cell Biol. 1993 Jan;13(1):257–265. doi: 10.1128/mcb.13.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Ragsdale C. W., Jr, Brockes J. P. Retinoids and their targets in vertebrate development. Curr Opin Cell Biol. 1991 Dec;3(6):928–934. doi: 10.1016/0955-0674(91)90109-c. [DOI] [PubMed] [Google Scholar]
  52. Reynolds K., Mezey E., Zimmer A. Activity of the beta-retinoic acid receptor promoter in transgenic mice. Mech Dev. 1991 Dec;36(1-2):15–29. doi: 10.1016/0925-4773(91)90068-h. [DOI] [PubMed] [Google Scholar]
  53. Ron D., Habener J. F. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev. 1992 Mar;6(3):439–453. doi: 10.1101/gad.6.3.439. [DOI] [PubMed] [Google Scholar]
  54. Rosner M. H., Vigano M. A., Ozato K., Timmons P. M., Poirier F., Rigby P. W., Staudt L. M. A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature. 1990 Jun 21;345(6277):686–692. doi: 10.1038/345686a0. [DOI] [PubMed] [Google Scholar]
  55. Schöler H. R., Ruppert S., Suzuki N., Chowdhury K., Gruss P. New type of POU domain in germ line-specific protein Oct-4. Nature. 1990 Mar 29;344(6265):435–439. doi: 10.1038/344435a0. [DOI] [PubMed] [Google Scholar]
  56. Segars J. H., Marks M. S., Hirschfeld S., Driggers P. H., Martinez E., Grippo J. F., Brown M., Wahli W., Ozato K. Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways. Mol Cell Biol. 1993 Apr;13(4):2258–2268. doi: 10.1128/mcb.13.4.2258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Segars J. H., Nagata T., Bours V., Medin J. A., Franzoso G., Blanco J. C., Drew P. D., Becker K. G., An J., Tang T. Retinoic acid induction of major histocompatibility complex class I genes in NTera-2 embryonal carcinoma cells involves induction of NF-kappa B (p50-p65) and retinoic acid receptor beta-retinoid X receptor beta heterodimers. Mol Cell Biol. 1993 Oct;13(10):6157–6169. doi: 10.1128/mcb.13.10.6157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Segraves W. A., Hogness D. S. The E75 ecdysone-inducible gene responsible for the 75B early puff in Drosophila encodes two new members of the steroid receptor superfamily. Genes Dev. 1990 Feb;4(2):204–219. doi: 10.1101/gad.4.2.204. [DOI] [PubMed] [Google Scholar]
  59. Seiler-Tuyns A., Walker P., Martinez E., Mérillat A. M., Givel F., Wahli W. Identification of estrogen-responsive DNA sequences by transient expression experiments in a human breast cancer cell line. Nucleic Acids Res. 1986 Nov 25;14(22):8755–8770. doi: 10.1093/nar/14.22.8755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Shen S., van der Saag P. T., Kruijer W. Dominant negative retinoic acid receptor beta. Mech Dev. 1993 Mar;40(3):177–189. doi: 10.1016/0925-4773(93)90075-9. [DOI] [PubMed] [Google Scholar]
  61. Simeone A., Acampora D., Nigro V., Faiella A., D'Esposito M., Stornaiuolo A., Mavilio F., Boncinelli E. Differential regulation by retinoic acid of the homeobox genes of the four HOX loci in human embryonal carcinoma cells. Mech Dev. 1991 Mar;33(3):215–227. doi: 10.1016/0925-4773(91)90029-6. [DOI] [PubMed] [Google Scholar]
  62. Tsai S., Bartelmez S., Heyman R., Damm K., Evans R., Collins S. J. A mutated retinoic acid receptor-alpha exhibiting dominant-negative activity alters the lineage development of a multipotent hematopoietic cell line. Genes Dev. 1992 Dec;6(12A):2258–2269. doi: 10.1101/gad.6.12a.2258. [DOI] [PubMed] [Google Scholar]
  63. Wang Y., Miksicek R. J. Identification of a dominant negative form of the human estrogen receptor. Mol Endocrinol. 1991 Nov;5(11):1707–1715. doi: 10.1210/mend-5-11-1707. [DOI] [PubMed] [Google Scholar]
  64. Yang-Yen H. F., Chiu R., Karin M. Elevation of AP1 activity during F9 cell differentiation is due to increased c-jun transcription. New Biol. 1990 Apr;2(4):351–361. [PubMed] [Google Scholar]
  65. Yu V. C., Delsert C., Andersen B., Holloway J. M., Devary O. V., När A. M., Kim S. Y., Boutin J. M., Glass C. K., Rosenfeld M. G. RXR beta: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. Cell. 1991 Dec 20;67(6):1251–1266. doi: 10.1016/0092-8674(91)90301-e. [DOI] [PubMed] [Google Scholar]
  66. Zelent A., Mendelsohn C., Kastner P., Krust A., Garnier J. M., Ruffenach F., Leroy P., Chambon P. Differentially expressed isoforms of the mouse retinoic acid receptor beta generated by usage of two promoters and alternative splicing. EMBO J. 1991 Jan;10(1):71–81. doi: 10.1002/j.1460-2075.1991.tb07922.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Zhang X. K., Lehmann J., Hoffmann B., Dawson M. I., Cameron J., Graupner G., Hermann T., Tran P., Pfahl M. Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid. Nature. 1992 Aug 13;358(6387):587–591. doi: 10.1038/358587a0. [DOI] [PubMed] [Google Scholar]
  68. Zimmer A., Zimmer A. Induction of a RAR beta 2-lacZ transgene by retinoic acid reflects the neuromeric organization of the central nervous system. Development. 1992 Dec;116(4):977–983. doi: 10.1242/dev.116.4.977. [DOI] [PubMed] [Google Scholar]
  69. de Groot R. P., Kruyt F. A., van der Saag P. T., Kruijer W. Ectopic expression of c-jun leads to differentiation of P19 embryonal carcinoma cells. EMBO J. 1990 Jun;9(6):1831–1837. doi: 10.1002/j.1460-2075.1990.tb08308.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. 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]

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