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. 1997 Apr 15;16(8):2014–2022. doi: 10.1093/emboj/16.8.2014

A CREB-binding site as a target for decapentaplegic signalling during Drosophila endoderm induction.

S Eresh 1, J Riese 1, D B Jackson 1, D Bohmann 1, M Bienz 1
PMCID: PMC1169804  PMID: 9155027

Abstract

Decapentaplegic (Dpp) is an extracellular signal of the transforming growth factor-beta family with multiple functions during Drosophila development. For example, it plays a key role in the embryo during endoderm induction. During this process, Dpp stimulates transcription of the homeotic genes Ultrabithorax in the visceral mesoderm and labial in the subjacent endoderm. Here, we show that a cAMP response element (CRE) from an Ultrabithorax enhancer mediates Dpp-responsive transcription in the embryonic midgut, and that endoderm expression from a labial enhancer depends on multiple CREs. Furthermore, the Drosophila CRE-binding protein dCREB-B binds to the Ultrabithorax CRE, and ubiquitous expression of a dominant-negative form of dCREB-B suppresses CRE-mediated reporter gene expression and reduces labial expression in the endoderm. Therefore, a CREB protein may act as a nuclear target, or as a partner of a nuclear target, for Dpp signalling in the embryonic midgut.

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Selected References

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

  1. Abel T., Bhatt R., Maniatis T. A Drosophila CREB/ATF transcriptional activator binds to both fat body- and liver-specific regulatory elements. Genes Dev. 1992 Mar;6(3):466–480. doi: 10.1101/gad.6.3.466. [DOI] [PubMed] [Google Scholar]
  2. Andrew D. J., Horner M. A., Petitt M. G., Smolik S. M., Scott M. P. Setting limits on homeotic gene function: restraint of Sex combs reduced activity by teashirt and other homeotic genes. EMBO J. 1994 Mar 1;13(5):1132–1144. doi: 10.1002/j.1460-2075.1994.tb06362.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Biggin M. D., Tjian R. Transcription factors that activate the Ultrabithorax promoter in developmentally staged extracts. Cell. 1988 Jun 3;53(5):699–711. doi: 10.1016/0092-8674(88)90088-8. [DOI] [PubMed] [Google Scholar]
  4. Bohmann D., Ellis M. C., Staszewski L. M., Mlodzik M. Drosophila Jun mediates Ras-dependent photoreceptor determination. Cell. 1994 Sep 23;78(6):973–986. doi: 10.1016/0092-8674(94)90273-9. [DOI] [PubMed] [Google Scholar]
  5. Brand A. H., Manoukian A. S., Perrimon N. Ectopic expression in Drosophila. Methods Cell Biol. 1994;44:635–654. doi: 10.1016/s0091-679x(08)60936-x. [DOI] [PubMed] [Google Scholar]
  6. Brand A. H., Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993 Jun;118(2):401–415. doi: 10.1242/dev.118.2.401. [DOI] [PubMed] [Google Scholar]
  7. Carlsson P., Waterman M. L., Jones K. A. The hLEF/TCF-1 alpha HMG protein contains a context-dependent transcriptional activation domain that induces the TCR alpha enhancer in T cells. Genes Dev. 1993 Dec;7(12A):2418–2430. doi: 10.1101/gad.7.12a.2418. [DOI] [PubMed] [Google Scholar]
  8. Cavener D. R. Comparison of the consensus sequence flanking translational start sites in Drosophila and vertebrates. Nucleic Acids Res. 1987 Feb 25;15(4):1353–1361. doi: 10.1093/nar/15.4.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chrivia J. C., Kwok R. P., Lamb N., Hagiwara M., Montminy M. R., Goodman R. H. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature. 1993 Oct 28;365(6449):855–859. doi: 10.1038/365855a0. [DOI] [PubMed] [Google Scholar]
  10. Ferguson E. L., Anderson K. V. Decapentaplegic acts as a morphogen to organize dorsal-ventral pattern in the Drosophila embryo. Cell. 1992 Oct 30;71(3):451–461. doi: 10.1016/0092-8674(92)90514-d. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Frasch M. Induction of visceral and cardiac mesoderm by ectodermal Dpp in the early Drosophila embryo. Nature. 1995 Mar 30;374(6521):464–467. doi: 10.1038/374464a0. [DOI] [PubMed] [Google Scholar]
  13. Giese K., Grosschedl R. LEF-1 contains an activation domain that stimulates transcription only in a specific context of factor-binding sites. EMBO J. 1993 Dec;12(12):4667–4676. doi: 10.1002/j.1460-2075.1993.tb06155.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ginty D. D., Bonni A., Greenberg M. E. Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB. Cell. 1994 Jun 3;77(5):713–725. doi: 10.1016/0092-8674(94)90055-8. [DOI] [PubMed] [Google Scholar]
  15. Gonzalez G. A., Montminy M. R. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell. 1989 Nov 17;59(4):675–680. doi: 10.1016/0092-8674(89)90013-5. [DOI] [PubMed] [Google Scholar]
  16. Green J. B., New H. V., Smith J. C. Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm. Cell. 1992 Nov 27;71(5):731–739. doi: 10.1016/0092-8674(92)90550-v. [DOI] [PubMed] [Google Scholar]
  17. Green J. B., Smith J. C. Graded changes in dose of a Xenopus activin A homologue elicit stepwise transitions in embryonic cell fate. Nature. 1990 Sep 27;347(6291):391–394. doi: 10.1038/347391a0. [DOI] [PubMed] [Google Scholar]
  18. Grieder N. C., Nellen D., Burke R., Basler K., Affolter M. Schnurri is required for Drosophila Dpp signaling and encodes a zinc finger protein similar to the mammalian transcription factor PRDII-BF1. Cell. 1995 Jun 2;81(5):791–800. doi: 10.1016/0092-8674(95)90540-5. [DOI] [PubMed] [Google Scholar]
  19. Gurdon J. B., Harger P., Mitchell A., Lemaire P. Activin signalling and response to a morphogen gradient. Nature. 1994 Oct 6;371(6497):487–492. doi: 10.1038/371487a0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Hai T., Curran T. Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3720–3724. doi: 10.1073/pnas.88.9.3720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jessell T. M., Melton D. A. Diffusible factors in vertebrate embryonic induction. Cell. 1992 Jan 24;68(2):257–270. doi: 10.1016/0092-8674(92)90469-s. [DOI] [PubMed] [Google Scholar]
  23. Jiang J., Struhl G. Protein kinase A and hedgehog signaling in Drosophila limb development. Cell. 1995 Feb 24;80(4):563–572. doi: 10.1016/0092-8674(95)90510-3. [DOI] [PubMed] [Google Scholar]
  24. Lalli E., Sassone-Corsi P. Signal transduction and gene regulation: the nuclear response to cAMP. J Biol Chem. 1994 Jul 1;269(26):17359–17362. [PubMed] [Google Scholar]
  25. Lawrence P. A., Struhl G. Morphogens, compartments, and pattern: lessons from drosophila? Cell. 1996 Jun 28;85(7):951–961. doi: 10.1016/s0092-8674(00)81297-0. [DOI] [PubMed] [Google Scholar]
  26. Lecuit T., Brook W. J., Ng M., Calleja M., Sun H., Cohen S. M. Two distinct mechanisms for long-range patterning by Decapentaplegic in the Drosophila wing. Nature. 1996 May 30;381(6581):387–393. doi: 10.1038/381387a0. [DOI] [PubMed] [Google Scholar]
  27. Li W., Ohlmeyer J. T., Lane M. E., Kalderon D. Function of protein kinase A in hedgehog signal transduction and Drosophila imaginal disc development. Cell. 1995 Feb 24;80(4):553–562. doi: 10.1016/0092-8674(95)90509-x. [DOI] [PubMed] [Google Scholar]
  28. Lloyd A., Yancheva N., Wasylyk B. Transformation suppressor activity of a Jun transcription factor lacking its activation domain. Nature. 1991 Aug 15;352(6336):635–638. doi: 10.1038/352635a0. [DOI] [PubMed] [Google Scholar]
  29. Nellen D., Burke R., Struhl G., Basler K. Direct and long-range action of a DPP morphogen gradient. Cell. 1996 May 3;85(3):357–368. doi: 10.1016/s0092-8674(00)81114-9. [DOI] [PubMed] [Google Scholar]
  30. Newfeld S. J., Chartoff E. H., Graff J. M., Melton D. A., Gelbart W. M. Mothers against dpp encodes a conserved cytoplasmic protein required in DPP/TGF-beta responsive cells. Development. 1996 Jul;122(7):2099–2108. doi: 10.1242/dev.122.7.2099. [DOI] [PubMed] [Google Scholar]
  31. Niswander L., Jeffrey S., Martin G. R., Tickle C. A positive feedback loop coordinates growth and patterning in the vertebrate limb. Nature. 1994 Oct 13;371(6498):609–612. doi: 10.1038/371609a0. [DOI] [PubMed] [Google Scholar]
  32. Noordermeer J., Johnston P., Rijsewijk F., Nusse R., Lawrence P. A. The consequences of ubiquitous expression of the wingless gene in the Drosophila embryo. Development. 1992 Nov;116(3):711–719. doi: 10.1242/dev.116.3.711. [DOI] [PubMed] [Google Scholar]
  33. Panganiban G. E., Reuter R., Scott M. P., Hoffmann F. M. A Drosophila growth factor homolog, decapentaplegic, regulates homeotic gene expression within and across germ layers during midgut morphogenesis. Development. 1990 Dec;110(4):1041–1050. doi: 10.1242/dev.110.4.1041. [DOI] [PubMed] [Google Scholar]
  34. Peverali F. A., Isaksson A., Papavassiliou A. G., Plastina P., Staszewski L. M., Mlodzik M., Bohmann D. Phosphorylation of Drosophila Jun by the MAP kinase rolled regulates photoreceptor differentiation. EMBO J. 1996 Aug 1;15(15):3943–3950. [PMC free article] [PubMed] [Google Scholar]
  35. Reuter R., Panganiban G. E., Hoffmann F. M., Scott M. P. Homeotic genes regulate the spatial expression of putative growth factors in the visceral mesoderm of Drosophila embryos. Development. 1990 Dec;110(4):1031–1040. doi: 10.1242/dev.110.4.1031. [DOI] [PubMed] [Google Scholar]
  36. Saari G., Bienz M. The structure of the Ultrabithorax promoter of Drosophila melanogaster. EMBO J. 1987 Jun;6(6):1775–1779. doi: 10.1002/j.1460-2075.1987.tb02430.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Small S., Kraut R., Hoey T., Warrior R., Levine M. Transcriptional regulation of a pair-rule stripe in Drosophila. Genes Dev. 1991 May;5(5):827–839. doi: 10.1101/gad.5.5.827. [DOI] [PubMed] [Google Scholar]
  38. Smith J. C. Mesoderm-inducing factors in early vertebrate development. EMBO J. 1993 Dec;12(12):4463–4470. doi: 10.1002/j.1460-2075.1993.tb06135.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Smith J. C., Price B. M., Van Nimmen K., Huylebroeck D. Identification of a potent Xenopus mesoderm-inducing factor as a homologue of activin A. Nature. 1990 Jun 21;345(6277):729–731. doi: 10.1038/345729a0. [DOI] [PubMed] [Google Scholar]
  40. Staehling-Hampton K., Hoffmann F. M. Ectopic decapentaplegic in the Drosophila midgut alters the expression of five homeotic genes, dpp, and wingless, causing specific morphological defects. Dev Biol. 1994 Aug;164(2):502–512. doi: 10.1006/dbio.1994.1219. [DOI] [PubMed] [Google Scholar]
  41. Studier F. W., Rosenberg A. H., Dunn J. J., Dubendorff J. W. Use of T7 RNA polymerase to direct expression of cloned genes. Methods Enzymol. 1990;185:60–89. doi: 10.1016/0076-6879(90)85008-c. [DOI] [PubMed] [Google Scholar]
  42. Thüringer F., Bienz M. Indirect autoregulation of a homeotic Drosophila gene mediated by extracellular signaling. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3899–3903. doi: 10.1073/pnas.90.9.3899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Tremml G., Bienz M. Induction of labial expression in the Drosophila endoderm: response elements for dpp signalling and for autoregulation. Development. 1992 Oct;116(2):447–456. doi: 10.1242/dev.116.2.447. [DOI] [PubMed] [Google Scholar]
  44. Yu X., Hoppler S., Eresh S., Bienz M. decapentaplegic, a target gene of the wingless signalling pathway in the Drosophila midgut. Development. 1996 Mar;122(3):849–858. doi: 10.1242/dev.122.3.849. [DOI] [PubMed] [Google Scholar]
  45. Zecca M., Basler K., Struhl G. Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing. Development. 1995 Aug;121(8):2265–2278. doi: 10.1242/dev.121.8.2265. [DOI] [PubMed] [Google Scholar]
  46. de Groot R. P., den Hertog J., Vandenheede J. R., Goris J., Sassone-Corsi P. Multiple and cooperative phosphorylation events regulate the CREM activator function. EMBO J. 1993 Oct;12(10):3903–3911. doi: 10.1002/j.1460-2075.1993.tb06068.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. van Dam H., Duyndam M., Rottier R., Bosch A., de Vries-Smits L., Herrlich P., Zantema A., Angel P., van der Eb A. J. Heterodimer formation of cJun and ATF-2 is responsible for induction of c-jun by the 243 amino acid adenovirus E1A protein. EMBO J. 1993 Feb;12(2):479–487. doi: 10.1002/j.1460-2075.1993.tb05680.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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