Abstract
Rat genomic regions covering c-myc were cloned from the DNA of both normal liver and two lines of Morris hepatomas, one of which had c-myc amplification. The three restriction maps showed perfect agreement within the overlapping regions. The 7 kb regions, which included the entire normal rat c-myc and the region 2.2 kb upstream, and one from the hepatomas, were sequenced and found to be identical. The coding regions of exons 2 and 3 were highly conserved between rat, mouse and man, but some differences in amino acids were noted. Exon 1 and the non-coding region of exon 3 showed limited homology between the three species. Rat exon 1 contained several nonsense codons in each frame and no ATG codon, indicating there to be no coding capacity in this exon. The 2.2 kb upstream regions and the introns compared showed unusual conservation between the rat and human genes. Some motifs, previously proposed as having a functional role in human c-myc, were also found in equivalent positions of the rat sequence. Nucleas S1 protection mapping revealed the second promoter to be preferentially used in most tissues or in hepatoma cells, and the second poly A addition signal to be the only one functional in all the RNA sources examined.
Full text
PDF

















Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abrams H. D., Rohrschneider L. R., Eisenman R. N. Nuclear location of the putative transforming protein of avian myelocytomatosis virus. Cell. 1982 Jun;29(2):427–439. doi: 10.1016/0092-8674(82)90159-3. [DOI] [PubMed] [Google Scholar]
- Battey J., Moulding C., Taub R., Murphy W., Stewart T., Potter H., Lenoir G., Leder P. The human c-myc oncogene: structural consequences of translocation into the IgH locus in Burkitt lymphoma. Cell. 1983 Oct;34(3):779–787. doi: 10.1016/0092-8674(83)90534-2. [DOI] [PubMed] [Google Scholar]
- Bentley D. L., Groudine M. A block to elongation is largely responsible for decreased transcription of c-myc in differentiated HL60 cells. Nature. 1986 Jun 12;321(6071):702–706. doi: 10.1038/321702a0. [DOI] [PubMed] [Google Scholar]
- Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
- Berk A. J., Sharp P. A. Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids. Cell. 1977 Nov;12(3):721–732. doi: 10.1016/0092-8674(77)90272-0. [DOI] [PubMed] [Google Scholar]
- 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]
- Birnstiel M. L., Busslinger M., Strub K. Transcription termination and 3' processing: the end is in site! Cell. 1985 Jun;41(2):349–359. doi: 10.1016/s0092-8674(85)80007-6. [DOI] [PubMed] [Google Scholar]
- Bishop J. M. Cellular oncogenes and retroviruses. Annu Rev Biochem. 1983;52:301–354. doi: 10.1146/annurev.bi.52.070183.001505. [DOI] [PubMed] [Google Scholar]
- Blanchard J. M., Piechaczyk M., Dani C., Chambard J. C., Franchi A., Pouyssegur J., Jeanteur P. c-myc gene is transcribed at high rate in G0-arrested fibroblasts and is post-transcriptionally regulated in response to growth factors. Nature. 1985 Oct 3;317(6036):443–445. doi: 10.1038/317443a0. [DOI] [PubMed] [Google Scholar]
- Briggs M. R., Kadonaga J. T., Bell S. P., Tjian R. Purification and biochemical characterization of the promoter-specific transcription factor, Sp1. Science. 1986 Oct 3;234(4772):47–52. doi: 10.1126/science.3529394. [DOI] [PubMed] [Google Scholar]
- Britten R. J. Rates of DNA sequence evolution differ between taxonomic groups. Science. 1986 Mar 21;231(4744):1393–1398. doi: 10.1126/science.3082006. [DOI] [PubMed] [Google Scholar]
- Chung J., Sinn E., Reed R. R., Leder P. Trans-acting elements modulate expression of the human c-myc gene in Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7918–7922. doi: 10.1073/pnas.83.20.7918. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Colby W. W., Chen E. Y., Smith D. H., Levinson A. D. Identification and nucleotide sequence of a human locus homologous to the v-myc oncogene of avian myelocytomatosis virus MC29. Nature. 1983 Feb 24;301(5902):722–725. doi: 10.1038/301722a0. [DOI] [PubMed] [Google Scholar]
- Deininger P. L. Random subcloning of sonicated DNA: application to shotgun DNA sequence analysis. Anal Biochem. 1983 Feb 15;129(1):216–223. doi: 10.1016/0003-2697(83)90072-6. [DOI] [PubMed] [Google Scholar]
- Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duesberg P. H., Bister K., Vogt P. K. The RNA of avian acute leukemia virus MC29. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4320–4324. doi: 10.1073/pnas.74.10.4320. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Einat M., Resnitzky D., Kimchi A. Close link between reduction of c-myc expression by interferon and, G0/G1 arrest. Nature. 1985 Feb 14;313(6003):597–600. doi: 10.1038/313597a0. [DOI] [PubMed] [Google Scholar]
- Enquist L., Sternberg N. In vitro packaging of lambda Dam vectors and their use in cloning DNA fragments. Methods Enzymol. 1979;68:281–298. doi: 10.1016/0076-6879(79)68020-5. [DOI] [PubMed] [Google Scholar]
- Floyd-Smith G., Slattery E., Lengyel P. Interferon action: RNA cleavage pattern of a (2'-5')oligoadenylate--dependent endonuclease. Science. 1981 May 29;212(4498):1030–1032. doi: 10.1126/science.6165080. [DOI] [PubMed] [Google Scholar]
- Frischauf A. M., Lehrach H., Poustka A., Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. doi: 10.1016/s0022-2836(83)80190-9. [DOI] [PubMed] [Google Scholar]
- Gazin C., Dupont de Dinechin S., Hampe A., Masson J. M., Martin P., Stehelin D., Galibert F. Nucleotide sequence of the human c-myc locus: provocative open reading frame within the first exon. EMBO J. 1984 Feb;3(2):383–387. doi: 10.1002/j.1460-2075.1984.tb01816.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gazin C., Rigolet M., Briand J. P., Van Regenmortel M. H., Galibert F. Immunochemical detection of proteins related to the human c-myc exon 1. EMBO J. 1986 Sep;5(9):2241–2250. doi: 10.1002/j.1460-2075.1986.tb04491.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenberg M. E., Ziff E. B. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. doi: 10.1038/311433a0. [DOI] [PubMed] [Google Scholar]
- Hayashi K., Makino R., Sugimura T. Amplification and over-expression of the c-myc gene in Morris hepatomas. Gan. 1984 Jun;75(6):475–478. [PubMed] [Google Scholar]
- Hayflick J., Seeburg P. H., Ohlsson R., Pfeifer-Ohlsson S., Watson D., Papas T., Duesberg P. H. Nucleotide sequence of two overlapping myc-related genes in avian carcinoma virus OK10 and their relation to the myc genes of other viruses and the cell. Proc Natl Acad Sci U S A. 1985 May;82(9):2718–2722. doi: 10.1073/pnas.82.9.2718. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kan N. C., Flordellis C. S., Garon C. F., Duesberg P. H., Papas T. S. Avian carcinoma virus MH2 contains a transformation-specific sequence, mht, and shares the myc sequence with MC29, CMII, and OK10 viruses. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6566–6570. doi: 10.1073/pnas.80.21.6566. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kanehisa M., Klein P., Greif P., DeLisi C. Computer analysis and structure prediction of nucleic acids and proteins. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):417–428. doi: 10.1093/nar/12.1part1.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keath E. J., Kelekar A., Cole M. D. Transcriptional activation of the translocated c-myc oncogene in mouse plasmacytomas: similar RNA levels in tumor and proliferating normal cells. Cell. 1984 Jun;37(2):521–528. doi: 10.1016/0092-8674(84)90382-9. [DOI] [PubMed] [Google Scholar]
- Klein G., Klein E. Evolution of tumours and the impact of molecular oncology. Nature. 1985 May 16;315(6016):190–195. doi: 10.1038/315190a0. [DOI] [PubMed] [Google Scholar]
- Kruijer W., Cooper J. A., Hunter T., Verma I. M. Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and protein. Nature. 1984 Dec 20;312(5996):711–716. doi: 10.1038/312711a0. [DOI] [PubMed] [Google Scholar]
- Linial M., Gunderson N., Groudine M. Enhanced transcription of c-myc in bursal lymphoma cells requires continuous protein synthesis. Science. 1985 Dec 6;230(4730):1126–1132. doi: 10.1126/science.2999973. [DOI] [PubMed] [Google Scholar]
- Makino R., Hayashi K., Sugimura T. C-myc transcript is induced in rat liver at a very early stage of regeneration or by cycloheximide treatment. Nature. 1984 Aug 23;310(5979):697–698. doi: 10.1038/310697a0. [DOI] [PubMed] [Google Scholar]
- Meijlink F., Curran T., Miller A. D., Verma I. M. Removal of a 67-base-pair sequence in the noncoding region of protooncogene fos converts it to a transforming gene. Proc Natl Acad Sci U S A. 1985 Aug;82(15):4987–4991. doi: 10.1073/pnas.82.15.4987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Nagata K., Guggenheimer R. A., Hurwitz J. Specific binding of a cellular DNA replication protein to the origin of replication of adenovirus DNA. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6177–6181. doi: 10.1073/pnas.80.20.6177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Needleman S. B., Wunsch C. D. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol. 1970 Mar;48(3):443–453. doi: 10.1016/0022-2836(70)90057-4. [DOI] [PubMed] [Google Scholar]
- Nepveu A., Marcu K. B. Intragenic pausing and anti-sense transcription within the murine c-myc locus. EMBO J. 1986 Nov;5(11):2859–2865. doi: 10.1002/j.1460-2075.1986.tb04580.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nishikura K., Goldflam S., Vuocolo G. A. Accurate and efficient transcription of human c-myc genes injected into Xenopus laevis oocytes. Mol Cell Biol. 1985 Jun;5(6):1434–1441. doi: 10.1128/mcb.5.6.1434. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pear W. S., Ingvarsson S., Steffen D., Münke M., Francke U., Bazin H., Klein G., Sümegi J. Multiple chromosomal rearrangements in a spontaneously arising t(6;7) rat immunocytoma juxtapose c-myc and immunoglobulin heavy chain sequences. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7376–7380. doi: 10.1073/pnas.83.19.7376. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Remmers E. F., Yang J. Q., Marcu K. B. A negative transcriptional control element located upstream of the murine c-myc gene. EMBO J. 1986 May;5(5):899–904. doi: 10.1002/j.1460-2075.1986.tb04301.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Shilo B. Z., Weinberg R. A. DNA sequences homologous to vertebrate oncogenes are conserved in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6789–6792. doi: 10.1073/pnas.78.11.6789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siebenlist U., Hennighausen L., Battey J., Leder P. Chromatin structure and protein binding in the putative regulatory region of the c-myc gene in Burkitt lymphoma. Cell. 1984 Jun;37(2):381–391. doi: 10.1016/0092-8674(84)90368-4. [DOI] [PubMed] [Google Scholar]
- Stanton L. W., Watt R., Marcu K. B. Translocation, breakage and truncated transcripts of c-myc oncogene in murine plasmacytomas. Nature. 1983 Jun 2;303(5916):401–406. doi: 10.1038/303401a0. [DOI] [PubMed] [Google Scholar]
- Stewart T. A., Bellvé A. R., Leder P. Transcription and promoter usage of the myc gene in normal somatic and spermatogenic cells. Science. 1984 Nov 9;226(4675):707–710. doi: 10.1126/science.6494906. [DOI] [PubMed] [Google Scholar]
- 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]
- Thompson C. B., Challoner P. B., Neiman P. E., Groudine M. Expression of the c-myb proto-oncogene during cellular proliferation. 1986 Jan 30-Feb 5Nature. 319(6052):374–380. doi: 10.1038/319374a0. [DOI] [PubMed] [Google Scholar]
- Vennström B., Moscovici C., Goodman H. M., Bishop J. M. Molecular cloning of the avian myelocytomatosis virus genome and recovery of infectious virus by transfection of chicken cells. J Virol. 1981 Aug;39(2):625–631. doi: 10.1128/jvi.39.2.625-631.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang A. H., Quigley G. J., Kolpak F. J., Crawford J. L., van Boom J. H., van der Marel G., Rich A. Molecular structure of a left-handed double helical DNA fragment at atomic resolution. Nature. 1979 Dec 13;282(5740):680–686. doi: 10.1038/282680a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Williams B. R., Golgher R. R., Brown R. E., Gilbert C. S., Kerr I. M. Natural occurrence of 2-5A in interferon-treated EMC virus-infected L cells. Nature. 1979 Dec 6;282(5739):582–586. doi: 10.1038/282582a0. [DOI] [PubMed] [Google Scholar]
- Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]