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. 1992 Dec 11;20(23):6393–6399. doi: 10.1093/nar/20.23.6393

A cyclic AMP response element is involved in retinoic acid-dependent RAR beta 2 promoter activation.

F A Kruyt 1, G Folkers 1, C E van den Brink 1, P T van der Saag 1
PMCID: PMC334532  PMID: 1335571

Abstract

Activation of the retinoic acid receptor (RAR) beta 2 promoter is known to be mediated by a RA response element located in the proximity of the TATA-box. By deletion studies in P19 embryonal carcinoma cells we have analyzed the RAR beta 2 promoter for the presence of additional regulatory elements. We found that the cyclic AMP response element-related motif, TGATGTCA at position -99 to -92, is able to enhance RA-dependent RAR beta 2 promoter activation. In addition we demonstrate that this element, designated CRE-beta 2, is functionally active as a CRE since it can bind members of the CREB/ATF transcription factor family and, moreover, mediates the stimulatory effect of cAMP on RA-dependent RAR beta 2 promoter activation in human foetal kidney 293 cells.

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Selected References

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

  1. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Berkenstam A., Vivanco Ruiz M. M., Barettino D., Horikoshi M., Stunnenberg H. G. Cooperativity in transactivation between retinoic acid receptor and TFIID requires an activity analogous to E1A. Cell. 1992 May 1;69(3):401–412. doi: 10.1016/0092-8674(92)90443-g. [DOI] [PubMed] [Google Scholar]
  5. Bokar J. A., Keri R. A., Farmerie T. A., Fenstermaker R. A., Andersen B., Hamernik D. L., Yun J., Wagner T., Nilson J. H. Expression of the glycoprotein hormone alpha-subunit gene in the placenta requires a functional cyclic AMP response element, whereas a different cis-acting element mediates pituitary-specific expression. Mol Cell Biol. 1989 Nov;9(11):5113–5122. doi: 10.1128/mcb.9.11.5113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Brockes J. Developmental biology. Reading the retinoid signals. Nature. 1990 Jun 28;345(6278):766–768. doi: 10.1038/345766a0. [DOI] [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. Dean D. C., Blakeley M. S., Newby R. F., Ghazal P., Hennighausen L., Bourgeois S. Forskolin inducibility and tissue-specific expression of the fibronectin promoter. Mol Cell Biol. 1989 Apr;9(4):1498–1506. doi: 10.1128/mcb.9.4.1498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Dollé P., Ruberte E., Leroy P., Morriss-Kay G., Chambon P. Retinoic acid receptors and cellular retinoid binding proteins. I. A systematic study of their differential pattern of transcription during mouse organogenesis. Development. 1990 Dec;110(4):1133–1151. doi: 10.1242/dev.110.4.1133. [DOI] [PubMed] [Google Scholar]
  12. Drust D. S., Troccoli N. M., Jameson J. L. Binding specificity of cyclic adenosine 3',5'-monophosphate-responsive element (CRE)-binding proteins and activating transcription factors to naturally occurring CRE sequence variants. Mol Endocrinol. 1991 Oct;5(10):1541–1551. doi: 10.1210/mend-5-10-1541. [DOI] [PubMed] [Google Scholar]
  13. Durston A. J., Timmermans J. P., Hage W. J., Hendriks H. F., de Vries N. J., Heideveld M., Nieuwkoop P. D. Retinoic acid causes an anteroposterior transformation in the developing central nervous system. Nature. 1989 Jul 13;340(6229):140–144. doi: 10.1038/340140a0. [DOI] [PubMed] [Google Scholar]
  14. Edwards M. K., McBurney M. W. The concentration of retinoic acid determines the differentiated cell types formed by a teratocarcinoma cell line. Dev Biol. 1983 Jul;98(1):187–191. doi: 10.1016/0012-1606(83)90348-2. [DOI] [PubMed] [Google Scholar]
  15. Eichele G. Retinoids and vertebrate limb pattern formation. Trends Genet. 1989 Aug;5(8):246–251. doi: 10.1016/0168-9525(89)90096-6. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Fenstermaker R. A., Farmerie T. A., Clay C. M., Hamernik D. L., Nilson J. H. Different combinations of regulatory elements may account for expression of the glycoprotein hormone alpha-subunit gene in primate and horse placenta. Mol Endocrinol. 1990 Oct;4(10):1480–1487. doi: 10.1210/mend-4-10-1480. [DOI] [PubMed] [Google Scholar]
  18. Flint J., Shenk T. Adenovirus E1A protein paradigm viral transactivator. Annu Rev Genet. 1989;23:141–161. doi: 10.1146/annurev.ge.23.120189.001041. [DOI] [PubMed] [Google Scholar]
  19. Flint K. J., Jones N. C. Differential regulation of three members of the ATF/CREB family of DNA-binding proteins. Oncogene. 1991 Nov;6(11):2019–2026. [PubMed] [Google Scholar]
  20. Foulkes N. S., Borrelli E., Sassone-Corsi P. CREM gene: use of alternative DNA-binding domains generates multiple antagonists of cAMP-induced transcription. Cell. 1991 Feb 22;64(4):739–749. doi: 10.1016/0092-8674(91)90503-q. [DOI] [PubMed] [Google Scholar]
  21. Fried M., Crothers D. M. Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis. Nucleic Acids Res. 1981 Dec 11;9(23):6505–6525. doi: 10.1093/nar/9.23.6505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. 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]
  24. Graham F. L., Smiley J., Russell W. C., Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol. 1977 Jul;36(1):59–74. doi: 10.1099/0022-1317-36-1-59. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Habener J. F. Cyclic AMP response element binding proteins: a cornucopia of transcription factors. Mol Endocrinol. 1990 Aug;4(8):1087–1094. doi: 10.1210/mend-4-8-1087. [DOI] [PubMed] [Google Scholar]
  27. Hai T. W., Liu F., Coukos W. J., Green M. R. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989 Dec;3(12B):2083–2090. doi: 10.1101/gad.3.12b.2083. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. 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]
  31. Karin M. Complexities of gene regulation by cAMP. Trends Genet. 1989 Mar;5(3):65–67. doi: 10.1016/0168-9525(89)90027-9. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. 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]
  35. Lee K. A., Bindereif A., Green M. R. A small-scale procedure for preparation of nuclear extracts that support efficient transcription and pre-mRNA splicing. Gene Anal Tech. 1988 Mar-Apr;5(2):22–31. doi: 10.1016/0735-0651(88)90023-4. [DOI] [PubMed] [Google Scholar]
  36. Lee W., Mitchell P., Tjian R. Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements. Cell. 1987 Jun 19;49(6):741–752. doi: 10.1016/0092-8674(87)90612-x. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. 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]
  39. 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]
  40. Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Maden M. Vitamin A and pattern formation in the regenerating limb. Nature. 1982 Feb 25;295(5851):672–675. doi: 10.1038/295672a0. [DOI] [PubMed] [Google Scholar]
  42. 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]
  43. Meijer D., Graus A., Kraay R., Langeveld A., Mulder M. P., Grosveld G. The octamer binding factor Oct6: cDNA cloning and expression in early embryonic cells. Nucleic Acids Res. 1990 Dec 25;18(24):7357–7365. doi: 10.1093/nar/18.24.7357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Moore C. C., Brentano S. T., Miller W. L. Human P450scc gene transcription is induced by cyclic AMP and repressed by 12-O-tetradecanoylphorbol-13-acetate and A23187 through independent cis elements. Mol Cell Biol. 1990 Nov;10(11):6013–6023. doi: 10.1128/mcb.10.11.6013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. 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]
  46. Ragsdale C. W., Jr, Petkovich M., Gates P. B., Chambon P., Brockes J. P. Identification of a novel retinoic acid receptor in regenerative tissues of the newt. Nature. 1989 Oct 19;341(6243):654–657. doi: 10.1038/341654a0. [DOI] [PubMed] [Google Scholar]
  47. Roesler W. J., Vandenbark G. R., Hanson R. W. Cyclic AMP and the induction of eukaryotic gene transcription. J Biol Chem. 1988 Jul 5;263(19):9063–9066. [PubMed] [Google Scholar]
  48. Ruberte E., Dolle P., Chambon P., Morriss-Kay G. Retinoic acid receptors and cellular retinoid binding proteins. II. Their differential pattern of transcription during early morphogenesis in mouse embryos. Development. 1991 Jan;111(1):45–60. doi: 10.1242/dev.111.1.45. [DOI] [PubMed] [Google Scholar]
  49. 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]
  50. Shen S., Kruyt F. A., den Hertog J., van der Saag P. T., Kruijer W. Mouse and human retinoic acid receptor beta 2 promoters: sequence comparison and localization of retinoic acid responsiveness. DNA Seq. 1991;2(2):111–119. doi: 10.3109/10425179109039679. [DOI] [PubMed] [Google Scholar]
  51. Sheng M., Thompson M. A., Greenberg M. E. CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. Science. 1991 Jun 7;252(5011):1427–1430. doi: 10.1126/science.1646483. [DOI] [PubMed] [Google Scholar]
  52. 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]
  53. Summerbell D., Maden M. Retinoic acid, a developmental signalling molecule. Trends Neurosci. 1990 Apr;13(4):142–147. doi: 10.1016/0166-2236(90)90006-v. [DOI] [PubMed] [Google Scholar]
  54. Tassios P. T., La Thangue N. B. A multiplicity of differentiation-regulated ATF site-binding activities in embryonal carcinoma cells with distinct sequence and promoter specificities. New Biol. 1990 Dec;2(12):1123–1134. [PubMed] [Google Scholar]
  55. 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]
  56. Tickle C., Alberts B., Wolpert L., Lee J. Local application of retinoic acid to the limb bond mimics the action of the polarizing region. Nature. 1982 Apr 8;296(5857):564–566. doi: 10.1038/296564a0. [DOI] [PubMed] [Google Scholar]
  57. Tora L., Gaub M. P., Mader S., Dierich A., Bellard M., Chambon P. Cell-specific activity of a GGTCA half-palindromic oestrogen-responsive element in the chicken ovalbumin gene promoter. EMBO J. 1988 Dec 1;7(12):3771–3778. doi: 10.1002/j.1460-2075.1988.tb03261.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. 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]
  59. Zelent A., Krust A., Petkovich M., Kastner P., Chambon P. Cloning of murine alpha and beta retinoic acid receptors and a novel receptor gamma predominantly expressed in skin. Nature. 1989 Jun 29;339(6227):714–717. doi: 10.1038/339714a0. [DOI] [PubMed] [Google Scholar]
  60. 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]
  61. Zhang X. K., Hoffmann B., Tran P. B., Graupner G., Pfahl M. Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors. Nature. 1992 Jan 30;355(6359):441–446. doi: 10.1038/355441a0. [DOI] [PubMed] [Google Scholar]
  62. Ziff E. B. Transcription factors: a new family gathers at the cAMP response site. Trends Genet. 1990 Mar;6(3):69–72. doi: 10.1016/0168-9525(90)90081-g. [DOI] [PubMed] [Google Scholar]
  63. 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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