Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1989 Dec 20;8(13):4273–4279. doi: 10.1002/j.1460-2075.1989.tb08613.x

DNA replication origin and transcriptional enhancer in c-myc gene share the c-myc protein binding sequences.

H Ariga 1, Y Imamura 1, S M Iguchi-Ariga 1
PMCID: PMC401633  PMID: 2686984

Abstract

We have previously reported that c-myc protein, or protein(s) complexed with c-myc protein, binds to the region upstream of the first exon of the c-myc gene and that this region contains an origin of cellular DNA replication (ori) and also a transcriptional enhancer. Here we show by Southwestern blotting that c-myc protein binds directly to a 7 bp sequence within the above region. Furthermore, we show that the c-myc protein binding sequences are indispensable for both ori and enhancer functions, but that additional sequences are required for maximal ori and enhancer activities. Thus, c-myc protein is a sequence specific factor which is apparently used both in initiation of DNA replication and in regulation of RNA transcription.

Full text

PDF
4273

Images in this article

Selected References

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

  1. Angel P., Allegretto E. A., Okino S. T., Hattori K., Boyle W. J., Hunter T., Karin M. Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. Nature. 1988 Mar 10;332(6160):166–171. doi: 10.1038/332166a0. [DOI] [PubMed] [Google Scholar]
  2. Ariga H., Itani T., Iguchi-Ariga S. M. Autonomous replicating sequences from mouse cells which can replicate in mouse cells in vivo and in vitro. Mol Cell Biol. 1987 Jan;7(1):1–6. doi: 10.1128/mcb.7.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bading H., Hansen J., Moelling K. Selective DNA binding of the human cellular myb protein isolated by immunoaffinity chromatography using a monoclonal antibody. Oncogene. 1987;1(4):395–401. [PubMed] [Google Scholar]
  4. Biedenkapp H., Borgmeyer U., Sippel A. E., Klempnauer K. H. Viral myb oncogene encodes a sequence-specific DNA-binding activity. Nature. 1988 Oct 27;335(6193):835–837. doi: 10.1038/335835a0. [DOI] [PubMed] [Google Scholar]
  5. Bohmann D., Bos T. J., Admon A., Nishimura T., Vogt P. K., Tjian R. Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science. 1987 Dec 4;238(4832):1386–1392. doi: 10.1126/science.2825349. [DOI] [PubMed] [Google Scholar]
  6. Braithwaite A. W., Sturzbecher H. W., Addison C., Palmer C., Rudge K., Jenkins J. R. Mouse p53 inhibits SV40 origin-dependent DNA replication. Nature. 1987 Oct 1;329(6138):458–460. doi: 10.1038/329458a0. [DOI] [PubMed] [Google Scholar]
  7. Chiu R., Boyle W. J., Meek J., Smeal T., Hunter T., Karin M. The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell. 1988 Aug 12;54(4):541–552. doi: 10.1016/0092-8674(88)90076-1. [DOI] [PubMed] [Google Scholar]
  8. Classon M., Henriksson M., Sümegi J., Klein G., Hammarskjöld M. L., Hammaskjöld M. L. Elevated c-myc expression facilitates the replication of SV40 DNA in human lymphoma cells. Nature. 1987 Nov 19;330(6145):272–274. doi: 10.1038/330272a0. [DOI] [PubMed] [Google Scholar]
  9. Dang C. V., McGuire M., Buckmire M., Lee W. M. Involvement of the 'leucine zipper' region in the oligomerization and transforming activity of human c-myc protein. Nature. 1989 Feb 16;337(6208):664–666. doi: 10.1038/337664a0. [DOI] [PubMed] [Google Scholar]
  10. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Gannon J. V., Lane D. P. p53 and DNA polymerase alpha compete for binding to SV40 T antigen. Nature. 1987 Oct 1;329(6138):456–458. doi: 10.1038/329456a0. [DOI] [PubMed] [Google Scholar]
  13. Garner M. M., Revzin A. A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system. Nucleic Acids Res. 1981 Jul 10;9(13):3047–3060. doi: 10.1093/nar/9.13.3047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  15. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  16. Iguchi-Ariga S. M., Itani T., Kiji Y., Ariga H. Possible function of the c-myc product: promotion of cellular DNA replication. EMBO J. 1987 Aug;6(8):2365–2371. doi: 10.1002/j.1460-2075.1987.tb02513.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Iguchi-Ariga S. M., Itani T., Yamaguchi M., Ariga H. c-myc protein can be substituted for SV40 T antigen in SV40 DNA replication. Nucleic Acids Res. 1987 Jun 25;15(12):4889–4899. doi: 10.1093/nar/15.12.4889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Iguchi-Ariga S. M., Okazaki T., Itani T., Ariga H. Cloning of the p53-dependent origin of cellular DNA replication. Oncogene. 1988 Nov;3(5):509–515. [PubMed] [Google Scholar]
  19. Iguchi-Ariga S. M., Okazaki T., Itani T., Ogata M., Sato Y., Ariga H. An initiation site of DNA replication with transcriptional enhancer activity present upstream of the c-myc gene. EMBO J. 1988 Oct;7(10):3135–3142. doi: 10.1002/j.1460-2075.1988.tb03180.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jones K. A., Kadonaga J. T., Rosenfeld P. J., Kelly T. J., Tjian R. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell. 1987 Jan 16;48(1):79–89. doi: 10.1016/0092-8674(87)90358-8. [DOI] [PubMed] [Google Scholar]
  21. Kouzarides T., Ziff E. The role of the leucine zipper in the fos-jun interaction. Nature. 1988 Dec 15;336(6200):646–651. doi: 10.1038/336646a0. [DOI] [PubMed] [Google Scholar]
  22. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Lüscher B., Kuenzel E. A., Krebs E. G., Eisenman R. N. Myc oncoproteins are phosphorylated by casein kinase II. EMBO J. 1989 Apr;8(4):1111–1119. doi: 10.1002/j.1460-2075.1989.tb03481.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Miskimins W. K., Roberts M. P., McClelland A., Ruddle F. H. Use of a protein-blotting procedure and a specific DNA probe to identify nuclear proteins that recognize the promoter region of the transferrin receptor gene. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6741–6744. doi: 10.1073/pnas.82.20.6741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Miyamoto C., Chizzonite R., Crowl R., Rupprecht K., Kramer R., Schaber M., Kumar G., Poonian M., Ju G. Molecular cloning and regulated expression of the human c-myc gene in Escherichia coli and Saccharomyces cerevisiae: comparison of the protein products. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7232–7236. doi: 10.1073/pnas.82.21.7232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Naoe T., Shiku H., Yamada K., Okazaki T., Kurosawa Y. Production of a truncated human c-myc protein which binds to DNA. FEBS Lett. 1988 Nov 21;240(1-2):49–54. doi: 10.1016/0014-5793(88)80338-7. [DOI] [PubMed] [Google Scholar]
  28. O'Neill E. A., Fletcher C., Burrow C. R., Heintz N., Roeder R. G., Kelly T. J. Transcription factor OTF-1 is functionally identical to the DNA replication factor NF-III. Science. 1988 Sep 2;241(4870):1210–1213. doi: 10.1126/science.3413485. [DOI] [PubMed] [Google Scholar]
  29. Rauscher F. J., 3rd, Cohen D. R., Curran T., Bos T. J., Vogt P. K., Bohmann D., Tjian R., Franza B. R., Jr Fos-associated protein p39 is the product of the jun proto-oncogene. Science. 1988 May 20;240(4855):1010–1016. doi: 10.1126/science.3130660. [DOI] [PubMed] [Google Scholar]
  30. Sassone-Corsi P., Lamph W. W., Kamps M., Verma I. M. fos-associated cellular p39 is related to nuclear transcription factor AP-1. Cell. 1988 Aug 12;54(4):553–560. doi: 10.1016/0092-8674(88)90077-3. [DOI] [PubMed] [Google Scholar]
  31. Schöler H. R., Gruss P. Specific interaction between enhancer-containing molecules and cellular components. Cell. 1984 Feb;36(2):403–411. doi: 10.1016/0092-8674(84)90233-2. [DOI] [PubMed] [Google Scholar]
  32. Sheiness D., Bishop J. M. DNA and RNA from uninfected vertebrate cells contain nucleotide sequences related to the putative transforming gene of avian myelocytomatosis virus. J Virol. 1979 Aug;31(2):514–521. doi: 10.1128/jvi.31.2.514-521.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  34. Stürzbecher H. W., Brain R., Maimets T., Addison C., Rudge K., Jenkins J. R. Mouse p53 blocks SV40 DNA replication in vitro and downregulates T antigen DNA helicase activity. Oncogene. 1988 Oct;3(4):405–413. [PubMed] [Google Scholar]
  35. Tapscott S. J., Davis R. L., Thayer M. J., Cheng P. F., Weintraub H., Lassar A. B. MyoD1: a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts. Science. 1988 Oct 21;242(4877):405–411. doi: 10.1126/science.3175662. [DOI] [PubMed] [Google Scholar]
  36. Umekawa H., Tamiya-Koizumi K., Takagi E., Ariga H., Kojima K., Yoshida S. Phospholipid modulates in vitro replication of autonomous replicating sequence from human cells. J Biochem. 1988 Sep;104(3):333–336. doi: 10.1093/oxfordjournals.jbchem.a122469. [DOI] [PubMed] [Google Scholar]
  37. Westin G., Gerster T., Müller M. M., Schaffner G., Schaffner W. OVEC, a versatile system to study transcription in mammalian cells and cell-free extracts. Nucleic Acids Res. 1987 Sep 11;15(17):6787–6798. doi: 10.1093/nar/15.17.6787. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES