Abstract
The chicken c-myc gene, as defined by its homology to the v-myc gene of MC29 virus, is comprised of two exons. Using the techniques of runoff transcription, primer extension, and S1 nuclease protection, we demonstrate that there is a third c-myc exon of approximately equal to 345 base pairs (bp) located 0.7 kbp upstream of the 5' end of the v-myc homology. This first exon is transcribed and present in myc mRNA in normal chicken cells. We also examined RNA from five cell lines derived from avian leukosis virus-induced bursal lymphomas. In all these lines, the level of transcription of the 2.2- to 2.5-kbp myc mRNA is increased 30- to 60-fold over normal cells. The myc mRNA in four of these lines also contains increased levels of the first noncoding exon, and evidence is presented that the long terminal repeat (LTR) in the vicinity of c-myc is functioning as an enhancer of c-myc transcription rather than as a promoter in several of these cell lines. In two cell lines in which the viral LTR has integrated between the first and second exons in the proper orientation for downstream promotion of myc, the LTR does not exhibit promoter function. The pattern of c-myc transcription observed by others in a vast majority of avian leukosis virus-induced neoplasms is not observed in any of the five cell lines examined.
Full text
PDF![53](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c6/396969/b5cbacf1b361/pnas00341-0067.png)
![54](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c6/396969/c50c7f6aa7e0/pnas00341-0068.png)
![55](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c6/396969/99208d5e4028/pnas00341-0069.png)
![56](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c6/396969/564cef706e5c/pnas00341-0070.png)
![57](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c6/396969/7d9cc133228f/pnas00341-0071.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akiyama Y., Kato S. Two cell lines from lymphomas of Marek's disease. Biken J. 1974 Sep;17(3):105–116. [PubMed] [Google Scholar]
- Alitalo K., Bishop J. M., Smith D. H., Chen E. Y., Colby W. W., Levinson A. D. Nucleotide sequence to the v-myc oncogene of avian retrovirus MC29. Proc Natl Acad Sci U S A. 1983 Jan;80(1):100–104. doi: 10.1073/pnas.80.1.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Banerji J., Rusconi S., Schaffner W. Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. Cell. 1981 Dec;27(2 Pt 1):299–308. doi: 10.1016/0092-8674(81)90413-x. [DOI] [PubMed] [Google Scholar]
- Dalla-Favera R., Bregni M., Erikson J., Patterson D., Gallo R. C., Croce C. M. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7824–7827. doi: 10.1073/pnas.79.24.7824. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dalla-Favera R., Martinotti S., Gallo R. C., Erikson J., Croce C. M. Translocation and rearrangements of the c-myc oncogene locus in human undifferentiated B-cell lymphomas. Science. 1983 Feb 25;219(4587):963–967. doi: 10.1126/science.6401867. [DOI] [PubMed] [Google Scholar]
- Dynan W. S., Tjian R. The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell. 1983 Nov;35(1):79–87. doi: 10.1016/0092-8674(83)90210-6. [DOI] [PubMed] [Google Scholar]
- Erikson J., ar-Rushdi A., Drwinga H. L., Nowell P. C., Croce C. M. Transcriptional activation of the translocated c-myc oncogene in burkitt lymphoma. Proc Natl Acad Sci U S A. 1983 Feb;80(3):820–824. doi: 10.1073/pnas.80.3.820. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fung Y. K., Fadly A. M., Crittenden L. B., Kung H. J. On the mechanism of retrovirus-induced avian lymphoid leukosis: deletion and integration of the proviruses. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3418–3422. doi: 10.1073/pnas.78.6.3418. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gonda T. J., Sheiness D. K., Bishop J. M. Transcripts from the cellular homologs of retroviral oncogenes: distribution among chicken tissues. Mol Cell Biol. 1982 Jun;2(6):617–624. doi: 10.1128/mcb.2.6.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Groudine M., Peretz M., Weintraub H. Transcriptional regulation of hemoglobin switching in chicken embryos. Mol Cell Biol. 1981 Mar;1(3):281–288. doi: 10.1128/mcb.1.3.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamlyn P. H., Rabbitts T. H. Translocation joins c-myc and immunoglobulin gamma 1 genes in a Burkitt lymphoma revealing a third exon in the c-myc oncogene. Nature. 1983 Jul 14;304(5922):135–139. doi: 10.1038/304135a0. [DOI] [PubMed] [Google Scholar]
- Hayward W. S., Neel B. G., Astrin S. M. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature. 1981 Apr 9;290(5806):475–480. doi: 10.1038/290475a0. [DOI] [PubMed] [Google Scholar]
- Hihara H., Shimizu T., Yamamoto H. Establishment of tumor cell lines cultured from chickens with avian lymphoid leukosis. Natl Inst Anim Health Q (Tokyo) 1974 Winter;14(4):163–173. [PubMed] [Google Scholar]
- Levinson B., Khoury G., Vande Woude G., Gruss P. Activation of SV40 genome by 72-base pair tandem repeats of Moloney sarcoma virus. Nature. 1982 Feb 18;295(5850):568–572. doi: 10.1038/295568a0. [DOI] [PubMed] [Google Scholar]
- Linial M. Two retroviruses with similar transforming genes exhibit differences in transforming potential. Virology. 1982 Jun;119(2):382–391. doi: 10.1016/0042-6822(82)90097-6. [DOI] [PubMed] [Google Scholar]
- Marcu K. B., Harris L. J., Stanton L. W., Erikson J., Watt R., Croce C. M. Transcriptionally active c-myc oncogene is contained within NIARD, a DNA sequence associated with chromosome translocations in B-cell neoplasia. Proc Natl Acad Sci U S A. 1983 Jan;80(2):519–523. doi: 10.1073/pnas.80.2.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marcu K. B., Harris L. J., Stanton L. W., Erikson J., Watt R., Croce C. M. Transcriptionally active c-myc oncogene is contained within NIARD, a DNA sequence associated with chromosome translocations in B-cell neoplasia. Proc Natl Acad Sci U S A. 1983 Jan;80(2):519–523. doi: 10.1073/pnas.80.2.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McKnight S. L., Gavis E. R., Kingsbury R., Axel R. Analysis of transcriptional regulatory signals of the HSV thymidine kinase gene: identification of an upstream control region. Cell. 1981 Aug;25(2):385–398. doi: 10.1016/0092-8674(81)90057-x. [DOI] [PubMed] [Google Scholar]
- McKnight S. L., Kingsbury R. C., Spence A., Smith M. The distal transcription signals of the herpesvirus tk gene share a common hexanucleotide control sequence. Cell. 1984 May;37(1):253–262. doi: 10.1016/0092-8674(84)90321-0. [DOI] [PubMed] [Google Scholar]
- McKnight S. L., Kingsbury R. Transcriptional control signals of a eukaryotic protein-coding gene. Science. 1982 Jul 23;217(4557):316–324. doi: 10.1126/science.6283634. [DOI] [PubMed] [Google Scholar]
- Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
- Neel B. G., Gasic G. P., Rogler C. E., Skalka A. M., Ju G., Hishinuma F., Papas T., Astrin S. M., Hayward W. S. Molecular analysis of the c-myc locus in normal tissue and in avian leukosis virus-induced lymphomas. J Virol. 1982 Oct;44(1):158–166. doi: 10.1128/jvi.44.1.158-166.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pachl C., Biegalke B., Linial M. RNA and protein encoded by MH2 virus: evidence for subgenomic expression of v-myc. J Virol. 1983 Jan;45(1):133–139. doi: 10.1128/jvi.45.1.133-139.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pachl C., Schubach W., Eisenman R., Linial M. Expression of c-myc RNA in bursal lymphoma cell lines: identification of c-myc-encoded proteins by hybrid-selected translation. Cell. 1983 Jun;33(2):335–344. doi: 10.1016/0092-8674(83)90415-4. [DOI] [PubMed] [Google Scholar]
- Payne G. S., Bishop J. M., Varmus H. E. Multiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas. Nature. 1982 Jan 21;295(5846):209–214. doi: 10.1038/295209a0. [DOI] [PubMed] [Google Scholar]
- Roussel M., Saule S., Lagrou C., Rommens C., Beug H., Graf T., Stehelin D. Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation. Nature. 1979 Oct 11;281(5731):452–455. doi: 10.1038/281452a0. [DOI] [PubMed] [Google Scholar]
- Saito H., Hayday A. C., Wiman K., Hayward W. S., Tonegawa S. Activation of the c-myc gene by translocation: a model for translational control. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7476–7480. doi: 10.1073/pnas.80.24.7476. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schubach W., Groudine M. Alteration of c-myc chromatin structure by avian leukosis virus integration. Nature. 1984 Feb 23;307(5953):702–708. doi: 10.1038/307702a0. [DOI] [PubMed] [Google Scholar]
- Schwartz D. E., Tizard R., Gilbert W. Nucleotide sequence of Rous sarcoma virus. Cell. 1983 Mar;32(3):853–869. doi: 10.1016/0092-8674(83)90071-5. [DOI] [PubMed] [Google Scholar]
- Sheiness D. K., Hughes S. H., Varmus H. E., Stubblefield E., Bishop J. M. The vertebrate homolog of the putative transforming gene of avian myelocytomatosis virus: characteristics of the DNA locus and its RNA transcript. Virology. 1980 Sep;105(2):415–424. doi: 10.1016/0042-6822(80)90042-2. [DOI] [PubMed] [Google Scholar]
- 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]
- Shen-Ong G. L., Keath E. J., Piccoli S. P., Cole M. D. Novel myc oncogene RNA from abortive immunoglobulin-gene recombination in mouse plasmacytomas. Cell. 1982 Dec;31(2 Pt 1):443–452. doi: 10.1016/0092-8674(82)90137-4. [DOI] [PubMed] [Google Scholar]
- Shih C. K., Linial M., Goodenow M. M., Hayward W. S. Nucleotide sequence 5' of the chicken c-myc coding region: localization of a noncoding exon that is absent from myc transcripts in most avian leukosis virus-induced lymphomas. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4697–4701. doi: 10.1073/pnas.81.15.4697. [DOI] [PMC free article] [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]
- Sutrave P., Bonner T. I., Rapp U. R., Jansen H. W., Patschinsky T., Bister K. Nucleotide sequence of avian retroviral oncogene v-mil: homologue of murine retroviral oncogene v-raf. Nature. 1984 May 3;309(5963):85–88. doi: 10.1038/309085a0. [DOI] [PubMed] [Google Scholar]
- Taub R., Kirsch I., Morton C., Lenoir G., Swan D., Tronick S., Aaronson S., Leder P. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7837–7841. doi: 10.1073/pnas.79.24.7837. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- White B. A., Bancroft F. C. Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. J Biol Chem. 1982 Aug 10;257(15):8569–8572. [PubMed] [Google Scholar]