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. 1992 Oct;12(10):4590–4600. doi: 10.1128/mcb.12.10.4590

Sequences in the human c-myc P2 promoter affect the elongation and premature termination of transcripts initiated from the upstream P1 promoter.

T Meulia 1, A Krumm 1, C Spencer 1, M Groudine 1
PMCID: PMC360386  PMID: 1406649

Abstract

A conditional block to transcription elongation provides one mechanism for controlling the steady-state levels of c-myc RNA in mammalian cells. Although prematurely terminated c-myc RNAs are not detectable in mammalian cells, truncated c-myc RNAs with 3' ends that map near the end of the first exon are transcribed from human c-myc templates injected into Xenopus oocytes germinal vesicles. A series of linker scanner and deletion mutants within the c-myc P2 promoter was tested in the Xenopus oocyte injection assay to determine the potential contribution of promoter elements to the elongation or premature termination of c-myc transcription. Although this analysis failed to identify sequences in the P2 promoter that significantly affect the elongation or termination of P2-initiated transcripts, our results suggest that sequences within the P2 promoter contribute to the premature termination of transcripts initiated at the upstream P1 promoter. A subset of these sequences is essential for the efficient elongation of P1-initiated transcripts through intrinsic sites of termination at the end of exon 1. These sequences affect P1 elongation when they are downstream of the site of initiation, and we hypothesize that they may be analogous to a class of prokaryotic elements required for antitermination.

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Selected References

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

  1. Ashfield R., Enriquez-Harris P., Proudfoot N. J. Transcriptional termination between the closely linked human complement genes C2 and factor B: common termination factor for C2 and c-myc? EMBO J. 1991 Dec;10(13):4197–4207. doi: 10.1002/j.1460-2075.1991.tb04998.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Asselin C., Nepveu A., Marcu K. B. Molecular requirements for transcriptional initiation of the murine c-myc gene. Oncogene. 1989 May;4(5):549–558. [PubMed] [Google Scholar]
  3. Ben-Asher E., Aloni Y. Transcription of minute virus of mice, an autonomous parvovirus, may be regulated by attenuation. J Virol. 1984 Oct;52(1):266–276. doi: 10.1128/jvi.52.1.266-276.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bentley D. L., Brown W. L., Groudine M. Accurate, TATA box-dependent polymerase III transcription from promoters of the c-myc gene in injected Xenopus oocytes. Genes Dev. 1989 Aug;3(8):1179–1189. doi: 10.1101/gad.3.8.1179. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Bentley D. L., Groudine M. Novel promoter upstream of the human c-myc gene and regulation of c-myc expression in B-cell lymphomas. Mol Cell Biol. 1986 Oct;6(10):3481–3489. doi: 10.1128/mcb.6.10.3481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bentley D. L., Groudine M. Sequence requirements for premature termination of transcription in the human c-myc gene. Cell. 1988 Apr 22;53(2):245–256. doi: 10.1016/0092-8674(88)90386-8. [DOI] [PubMed] [Google Scholar]
  8. Boorstein W. R., Craig E. A. Primer extension analysis of RNA. Methods Enzymol. 1989;180:347–369. doi: 10.1016/0076-6879(89)80111-9. [DOI] [PubMed] [Google Scholar]
  9. Chang Y., Spicer D. B., Sonenshein G. E. Effects of IL-3 on promoter usage, attenuation and antisense transcription of the c-myc oncogene in the IL-3-dependent Ba/F3 early pre-B cell line. Oncogene. 1991 Nov;6(11):1979–1982. [PubMed] [Google Scholar]
  10. Eick D., Berger R., Polack A., Bornkamm G. W. Transcription of c-myc in human mononuclear cells is regulated by an elongation block. Oncogene. 1987;2(1):61–65. [PubMed] [Google Scholar]
  11. Eick D., Bornkamm G. W. Transcriptional arrest within the first exon is a fast control mechanism in c-myc gene expression. Nucleic Acids Res. 1986 Nov 11;14(21):8331–8346. doi: 10.1093/nar/14.21.8331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Eick D., Polack A., Kofler E., Lenoir G. M., Rickinson A. B., Bornkamm G. W. Expression of P0- and P3-RNA from the normal and translocated c-myc allele in Burkitt's lymphoma cells. Oncogene. 1990 Sep;5(9):1397–1402. [PubMed] [Google Scholar]
  13. Hay N., Skolnik-David H., Aloni Y. Attenuation in the control of SV40 gene expression. Cell. 1982 May;29(1):183–193. doi: 10.1016/0092-8674(82)90102-7. [DOI] [PubMed] [Google Scholar]
  14. Hiebert S. W., Lipp M., Nevins J. R. E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor. Proc Natl Acad Sci U S A. 1989 May;86(10):3594–3598. doi: 10.1073/pnas.86.10.3594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kephart D. D., Marshall N. F., Price D. H. Stability of Drosophila RNA polymerase II elongation complexes in vitro. Mol Cell Biol. 1992 May;12(5):2067–2077. doi: 10.1128/mcb.12.5.2067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kerppola T. K., Kane C. M. RNA polymerase: regulation of transcript elongation and termination. FASEB J. 1991 Oct;5(13):2833–2842. doi: 10.1096/fasebj.5.13.1916107. [DOI] [PubMed] [Google Scholar]
  17. Lindsten T., June C. H., Thompson C. B. Multiple mechanisms regulate c-myc gene expression during normal T cell activation. EMBO J. 1988 Sep;7(9):2787–2794. doi: 10.1002/j.1460-2075.1988.tb03133.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. London L., Keene R. G., Landick R. Analysis of premature termination in c-myc during transcription by RNA polymerase II in a HeLa nuclear extract. Mol Cell Biol. 1991 Sep;11(9):4599–4615. doi: 10.1128/mcb.11.9.4599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Maderious A., Chen-Kiang S. Pausing and premature termination of human RNA polymerase II during transcription of adenovirus in vivo and in vitro. Proc Natl Acad Sci U S A. 1984 Oct;81(19):5931–5935. doi: 10.1073/pnas.81.19.5931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mechti N., Piechaczyk M., Blanchard J. M., Marty L., Bonnieu A., Jeanteur P., Lebleu B. Transcriptional and post-transcriptional regulation of c-myc expression during the differentiation of murine erythroleukemia Friend cells. Nucleic Acids Res. 1986 Dec 22;14(24):9653–9666. doi: 10.1093/nar/14.24.9653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Miller H., Asselin C., Dufort D., Yang J. Q., Gupta K., Marcu K. B., Nepveu A. A cis-acting element in the promoter region of the murine c-myc gene is necessary for transcriptional block. Mol Cell Biol. 1989 Dec;9(12):5340–5349. doi: 10.1128/mcb.9.12.5340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mok M., Maderious A., Chen-Kiang S. Premature termination by human RNA polymerase II occurs temporally in the adenovirus major late transcriptional unit. Mol Cell Biol. 1984 Oct;4(10):2031–2040. doi: 10.1128/mcb.4.10.2031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Nishikura K. Sequences involved in accurate and efficient transcription of human c-myc genes microinjected into frog oocytes. Mol Cell Biol. 1986 Nov;6(11):4093–4098. doi: 10.1128/mcb.6.11.4093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Proudfoot N. J. Transcriptional interference and termination between duplicated alpha-globin gene constructs suggests a novel mechanism for gene regulation. Nature. 1986 Aug 7;322(6079):562–565. doi: 10.1038/322562a0. [DOI] [PubMed] [Google Scholar]
  26. Ray R., Miller D. M. Cloning and characterization of a human c-myc promoter-binding protein. Mol Cell Biol. 1991 Apr;11(4):2154–2161. doi: 10.1128/mcb.11.4.2154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Resnekov O., Aloni Y. RNA polymerase II is capable of pausing and prematurely terminating transcription at a precise location in vivo and in vitro. Proc Natl Acad Sci U S A. 1989 Jan;86(1):12–16. doi: 10.1073/pnas.86.1.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Roberts J. W. Phage lambda and the regulation of transcription termination. Cell. 1988 Jan 15;52(1):5–6. doi: 10.1016/0092-8674(88)90523-5. [DOI] [PubMed] [Google Scholar]
  29. Roberts S., Bentley D. L. Distinct modes of transcription read through or terminate at the c-myc attenuator. EMBO J. 1992 Mar;11(3):1085–1093. doi: 10.1002/j.1460-2075.1992.tb05147.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Roberts S., Purton T., Bentley D. L. A protein-binding site in the c-myc promoter functions as a terminator of RNA polymerase II transcription. Genes Dev. 1992 Aug;6(8):1562–1574. doi: 10.1101/gad.6.8.1562. [DOI] [PubMed] [Google Scholar]
  31. Spencer C. A., Groudine M. Control of c-myc regulation in normal and neoplastic cells. Adv Cancer Res. 1991;56:1–48. doi: 10.1016/s0065-230x(08)60476-5. [DOI] [PubMed] [Google Scholar]
  32. Spencer C. A., Groudine M. Transcription elongation and eukaryotic gene regulation. Oncogene. 1990 Jun;5(6):777–785. [PubMed] [Google Scholar]
  33. Spencer C. A., LeStrange R. C., Novak U., Hayward W. S., Groudine M. The block to transcription elongation is promoter dependent in normal and Burkitt's lymphoma c-myc alleles. Genes Dev. 1990 Jan;4(1):75–88. doi: 10.1101/gad.4.1.75. [DOI] [PubMed] [Google Scholar]
  34. Thalmeier K., Synovzik H., Mertz R., Winnacker E. L., Lipp M. Nuclear factor E2F mediates basic transcription and trans-activation by E1a of the human MYC promoter. Genes Dev. 1989 Apr;3(4):527–536. doi: 10.1101/gad.3.4.527. [DOI] [PubMed] [Google Scholar]
  35. Vieira J., Messing J. Production of single-stranded plasmid DNA. Methods Enzymol. 1987;153:3–11. doi: 10.1016/0076-6879(87)53044-0. [DOI] [PubMed] [Google Scholar]
  36. Wright S., Bishop J. M. DNA sequences that mediate attenuation of transcription from the mouse protooncogene myc. Proc Natl Acad Sci U S A. 1989 Jan;86(2):505–509. doi: 10.1073/pnas.86.2.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wright S., Mirels L. F., Calayag M. C., Bishop J. M. Premature termination of transcription from the P1 promoter of the mouse c-myc gene. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11383–11387. doi: 10.1073/pnas.88.24.11383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Yanofsky C. Transcription attenuation. J Biol Chem. 1988 Jan 15;263(2):609–612. [PubMed] [Google Scholar]
  39. ar-Rushdi A., Nishikura K., Erikson J., Watt R., Rovera G., Croce C. M. Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma. Science. 1983 Oct 28;222(4622):390–393. doi: 10.1126/science.6414084. [DOI] [PubMed] [Google Scholar]

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