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. 1990 May;10(5):2017–2026. doi: 10.1128/mcb.10.5.2017

Organization and expression of the chicken N-myc gene.

S Sawai 1, K Kato 1, Y Wakamatsu 1, H Kondoh 1
PMCID: PMC360548  PMID: 2183017

Abstract

We cloned the chicken N-myc gene and analyzed its structure and expression. We found that it consisted of three exons with coding regions in exons 2 and 3. Comparison to mammalian N-myc genomic sequence indicated that nucleotide sequences of the 5'-flanking region, noncoding exon 1, and introns were not conserved, but coding and 3' noncoding sequences showed significant homology to mammalian N-myc. Alignment of deduced amino acid sequences of chicken and mammalian N-myc proteins revealed nine conserved domains interrupted by different lengths of nonhomologous sequences. Two of the domains were specific to N-myc proteins, and the other seven were common to c-myc proteins. Northern blot (immunoblot) and in situ hybridization analyses of 3.5-day-old chicken embryos revealed that high-level expression of the N-myc gene was confirmed to certain tissues, e.g., the central nervous system, neural crest derivatives, and mesenchyme of limb buds. In the beak and limb primordia, N-myc expression in the mesenchyme was higher toward the distal end, suggesting possible involvement in positional assignment of the tissue within the rudimentary structures.

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Selected References

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

  1. Adamson E. D. Oncogenes in development. Development. 1987 Apr;99(4):449–471. doi: 10.1242/dev.99.4.449. [DOI] [PubMed] [Google Scholar]
  2. Bernard O., Cory S., Gerondakis S., Webb E., Adams J. M. Sequence of the murine and human cellular myc oncogenes and two modes of myc transcription resulting from chromosome translocation in B lymphoid tumours. EMBO J. 1983;2(12):2375–2383. doi: 10.1002/j.1460-2075.1983.tb01749.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Birrer M. J., Segal S., DeGreve J. S., Kaye F., Sausville E. A., Minna J. D. L-myc cooperates with ras to transform primary rat embryo fibroblasts. Mol Cell Biol. 1988 Jun;8(6):2668–2673. doi: 10.1128/mcb.8.6.2668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Braun T., Buschhausen-Denker G., Bober E., Tannich E., Arnold H. H. A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T1/2 fibroblasts. EMBO J. 1989 Mar;8(3):701–709. doi: 10.1002/j.1460-2075.1989.tb03429.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Caput D., Beutler B., Hartog K., Thayer R., Brown-Shimer S., Cerami A. Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1670–1674. doi: 10.1073/pnas.83.6.1670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Caudy M., Vässin H., Brand M., Tuma R., Jan L. Y., Jan Y. N. daughterless, a Drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex. Cell. 1988 Dec 23;55(6):1061–1067. doi: 10.1016/0092-8674(88)90250-4. [DOI] [PubMed] [Google Scholar]
  7. Cox K. H., DeLeon D. V., Angerer L. M., Angerer R. C. Detection of mrnas in sea urchin embryos by in situ hybridization using asymmetric RNA probes. Dev Biol. 1984 Feb;101(2):485–502. doi: 10.1016/0012-1606(84)90162-3. [DOI] [PubMed] [Google Scholar]
  8. Dang C. V., Lee W. M. Identification of the human c-myc protein nuclear translocation signal. Mol Cell Biol. 1988 Oct;8(10):4048–4054. doi: 10.1128/mcb.8.10.4048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dang C. V., van Dam H., Buckmire M., Lee W. M. DNA-binding domain of human c-Myc produced in Escherichia coli. Mol Cell Biol. 1989 Jun;9(6):2477–2486. doi: 10.1128/mcb.9.6.2477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Davis R. L., Weintraub H., Lassar A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987 Dec 24;51(6):987–1000. doi: 10.1016/0092-8674(87)90585-x. [DOI] [PubMed] [Google Scholar]
  11. DePinho R. A., Hatton K. S., Tesfaye A., Yancopoulos G. D., Alt F. W. The human myc gene family: structure and activity of L-myc and an L-myc pseudogene. Genes Dev. 1987 Dec;1(10):1311–1326. doi: 10.1101/gad.1.10.1311. [DOI] [PubMed] [Google Scholar]
  12. DePinho R. A., Legouy E., Feldman L. B., Kohl N. E., Yancopoulos G. D., Alt F. W. Structure and expression of the murine N-myc gene. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1827–1831. doi: 10.1073/pnas.83.6.1827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Downs K. M., Martin G. R., Bishop J. M. Contrasting patterns of myc and N-myc expression during gastrulation of the mouse embryo. Genes Dev. 1989 Jun;3(6):860–869. doi: 10.1101/gad.3.6.860. [DOI] [PubMed] [Google Scholar]
  14. Heine U., Munoz E. F., Flanders K. C., Ellingsworth L. R., Lam H. Y., Thompson N. L., Roberts A. B., Sporn M. B. Role of transforming growth factor-beta in the development of the mouse embryo. J Cell Biol. 1987 Dec;105(6 Pt 2):2861–2876. doi: 10.1083/jcb.105.6.2861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hill R. E., Jones P. F., Rees A. R., Sime C. M., Justice M. J., Copeland N. G., Jenkins N. A., Graham E., Davidson D. R. A new family of mouse homeo box-containing genes: molecular structure, chromosomal location, and developmental expression of Hox-7.1. Genes Dev. 1989 Jan;3(1):26–37. doi: 10.1101/gad.3.1.26. [DOI] [PubMed] [Google Scholar]
  16. Ingvarsson S., Asker C., Axelson H., Klein G., Sümegi J. Structure and expression of B-myc, a new member of the myc gene family. Mol Cell Biol. 1988 Aug;8(8):3168–3174. doi: 10.1128/mcb.8.8.3168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jaffredo T., Vandenbunder B., Dieterlen-Lièvre F. In situ study of c-myc protein expression during avian development. Development. 1989 Apr;105(4):679–695. doi: 10.1242/dev.105.4.679. [DOI] [PubMed] [Google Scholar]
  18. Jakobovits A., Schwab M., Bishop J. M., Martin G. R. Expression of N-myc in teratocarcinoma stem cells and mouse embryos. Nature. 1985 Nov 14;318(6042):188–191. doi: 10.1038/318188a0. [DOI] [PubMed] [Google Scholar]
  19. Johnson P. F., McKnight S. L. Eukaryotic transcriptional regulatory proteins. Annu Rev Biochem. 1989;58:799–839. doi: 10.1146/annurev.bi.58.070189.004055. [DOI] [PubMed] [Google Scholar]
  20. Katoh K., Sawai S., Ueno K., Kondoh H. Complete nucleotide sequence and exon-intron boundaries of the 5' non-coding region of the mouse N-myc gene. Nucleic Acids Res. 1988 Apr 25;16(8):3589–3589. doi: 10.1093/nar/16.8.3589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kaye F., Battey J., Nau M., Brooks B., Seifter E., De Greve J., Birrer M., Sausville E., Minna J. Structure and expression of the human L-myc gene reveal a complex pattern of alternative mRNA processing. Mol Cell Biol. 1988 Jan;8(1):186–195. doi: 10.1128/mcb.8.1.186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kohl N. E., Kanda N., Schreck R. R., Bruns G., Latt S. A., Gilbert F., Alt F. W. Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell. 1983 Dec;35(2 Pt 1):359–367. doi: 10.1016/0092-8674(83)90169-1. [DOI] [PubMed] [Google Scholar]
  23. Kohl N. E., Legouy E., DePinho R. A., Nisen P. D., Smith R. K., Gee C. E., Alt F. W. Human N-myc is closely related in organization and nucleotide sequence to c-myc. Nature. 1986 Jan 2;319(6048):73–77. doi: 10.1038/319073a0. [DOI] [PubMed] [Google Scholar]
  24. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  25. Landschulz W. H., Johnson P. F., McKnight S. L. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science. 1988 Jun 24;240(4860):1759–1764. doi: 10.1126/science.3289117. [DOI] [PubMed] [Google Scholar]
  26. Melton D. W., Konecki D. S., Brennand J., Caskey C. T. Structure, expression, and mutation of the hypoxanthine phosphoribosyltransferase gene. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2147–2151. doi: 10.1073/pnas.81.7.2147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mizusawa S., Nishimura S., Seela F. Improvement of the dideoxy chain termination method of DNA sequencing by use of deoxy-7-deazaguanosine triphosphate in place of dGTP. Nucleic Acids Res. 1986 Feb 11;14(3):1319–1324. doi: 10.1093/nar/14.3.1319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mugrauer G., Alt F. W., Ekblom P. N-myc proto-oncogene expression during organogenesis in the developing mouse as revealed by in situ hybridization. J Cell Biol. 1988 Oct;107(4):1325–1335. doi: 10.1083/jcb.107.4.1325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Murre C., McCaw P. S., Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989 Mar 10;56(5):777–783. doi: 10.1016/0092-8674(89)90682-x. [DOI] [PubMed] [Google Scholar]
  30. Mäkelä T. P., Saksela K., Alitalo K. Two N-myc polypeptides with distinct amino termini encoded by the second and third exons of the gene. Mol Cell Biol. 1989 Apr;9(4):1545–1552. doi: 10.1128/mcb.9.4.1545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Newman S. A. Lineage and pattern in the developing vertebrate limb. Trends Genet. 1988 Dec;4(12):329–332. doi: 10.1016/0168-9525(88)90051-0. [DOI] [PubMed] [Google Scholar]
  32. Nottenburg C., Varmus H. E. Features of the chicken c-myc gene that influence the structure of c-myc RNA in normal cells and bursal lymphomas. Mol Cell Biol. 1986 Aug;6(8):2800–2806. doi: 10.1128/mcb.6.8.2800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Persson H., Leder P. Nuclear localization and DNA binding properties of a protein expressed by human c-myc oncogene. Science. 1984 Aug 17;225(4663):718–721. doi: 10.1126/science.6463648. [DOI] [PubMed] [Google Scholar]
  34. Ramsay G., Stanton L., Schwab M., Bishop J. M. Human proto-oncogene N-myc encodes nuclear proteins that bind DNA. Mol Cell Biol. 1986 Dec;6(12):4450–4457. doi: 10.1128/mcb.6.12.4450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Reynolds G. A., Basu S. K., Osborne T. F., Chin D. J., Gil G., Brown M. S., Goldstein J. L., Luskey K. L. HMG CoA reductase: a negatively regulated gene with unusual promoter and 5' untranslated regions. Cell. 1984 Aug;38(1):275–285. doi: 10.1016/0092-8674(84)90549-x. [DOI] [PubMed] [Google Scholar]
  36. Robert B., Sassoon D., Jacq B., Gehring W., Buckingham M. Hox-7, a mouse homeobox gene with a novel pattern of expression during embryogenesis. EMBO J. 1989 Jan;8(1):91–100. doi: 10.1002/j.1460-2075.1989.tb03352.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rogers S., Wells R., Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. doi: 10.1126/science.2876518. [DOI] [PubMed] [Google Scholar]
  38. Schmid P., Schulz W. A., Hameister H. Dynamic expression pattern of the myc protooncogene in midgestation mouse embryos. Science. 1989 Jan 13;243(4888):226–229. doi: 10.1126/science.2911736. [DOI] [PubMed] [Google Scholar]
  39. Schwab M., Alitalo K., Klempnauer K. H., Varmus H. E., Bishop J. M., Gilbert F., Brodeur G., Goldstein M., Trent J. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature. 1983 Sep 15;305(5931):245–248. doi: 10.1038/305245a0. [DOI] [PubMed] [Google Scholar]
  40. 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. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  41. Slamon D. J., Boone T. C., Seeger R. C., Keith D. E., Chazin V., Lee H. C., Souza L. M. Identification and characterization of the protein encoded by the human N-myc oncogene. Science. 1986 May 9;232(4751):768–772. doi: 10.1126/science.3008339. [DOI] [PubMed] [Google Scholar]
  42. Stanton L. W., Schwab M., Bishop J. M. Nucleotide sequence of the human N-myc gene. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1772–1776. doi: 10.1073/pnas.83.6.1772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Stone J., de Lange T., Ramsay G., Jakobovits E., Bishop J. M., Varmus H., Lee W. Definition of regions in human c-myc that are involved in transformation and nuclear localization. Mol Cell Biol. 1987 May;7(5):1697–1709. doi: 10.1128/mcb.7.5.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Taya Y., Mizusawa S., Nishimura S. Nucleotide sequence of the coding region of the mouse N-myc gene. EMBO J. 1986 Jun;5(6):1215–1219. doi: 10.1002/j.1460-2075.1986.tb04349.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Ueno K., Katoh K., Kondoh H. Subnuclear localization and antitransforming activity of N-myc:beta-galactosidase fusion proteins. Mol Cell Biol. 1988 Oct;8(10):4529–4532. doi: 10.1128/mcb.8.10.4529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Valerio D., Duyvesteyn M. G., Dekker B. M., Weeda G., Berkvens T. M., van der Voorn L., van Ormondt H., van der Eb A. J. Adenosine deaminase: characterization and expression of a gene with a remarkable promoter. EMBO J. 1985 Feb;4(2):437–443. doi: 10.1002/j.1460-2075.1985.tb03648.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Villares R., Cabrera C. V. The achaete-scute gene complex of D. melanogaster: conserved domains in a subset of genes required for neurogenesis and their homology to myc. Cell. 1987 Jul 31;50(3):415–424. doi: 10.1016/0092-8674(87)90495-8. [DOI] [PubMed] [Google Scholar]
  48. Watson D. K., Reddy E. P., Duesberg P. H., Papas T. S. Nucleotide sequence analysis of the chicken c-myc gene reveals homologous and unique coding regions by comparison with the transforming gene of avian myelocytomatosis virus MC29, delta gag-myc. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2146–2150. doi: 10.1073/pnas.80.8.2146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Watt R. A., Shatzman A. R., Rosenberg M. Expression and characterization of the human c-myc DNA-binding protein. Mol Cell Biol. 1985 Mar;5(3):448–456. doi: 10.1128/mcb.5.3.448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Wedden S. E., Ralphs J. R., Tickle C. Pattern formation in the facial primordia. Development. 1988;103 (Suppl):31–40. doi: 10.1242/dev.103.Supplement.31. [DOI] [PubMed] [Google Scholar]
  51. Wright W. E., Sassoon D. A., Lin V. K. Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD. Cell. 1989 Feb 24;56(4):607–617. doi: 10.1016/0092-8674(89)90583-7. [DOI] [PubMed] [Google Scholar]
  52. Yancopoulos G. D., Nisen P. D., Tesfaye A., Kohl N. E., Goldfarb M. P., Alt F. W. N-myc can cooperate with ras to transform normal cells in culture. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5455–5459. doi: 10.1073/pnas.82.16.5455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Zimmerman K. A., Yancopoulos G. D., Collum R. G., Smith R. K., Kohl N. E., Denis K. A., Nau M. M., Witte O. N., Toran-Allerand D., Gee C. E. Differential expression of myc family genes during murine development. 1986 Feb 27-Mar 5Nature. 319(6056):780–783. doi: 10.1038/319780a0. [DOI] [PubMed] [Google Scholar]

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