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. 1984 Aug;3(8):1891–1899. doi: 10.1002/j.1460-2075.1984.tb02064.x

Modulation of enhancer activity by the hormone responsive regulatory element from mouse mammary tumor virus.

M C Ostrowski, A L Huang, M Kessel, R G Wolford, G L Hager
PMCID: PMC557614  PMID: 6090130

Abstract

Addition of the transcriptional enhancers present in the U3 region of the Harvey murine sarcoma virus (HaMuSV) long terminal repeat (LTR) to recombinant chimeras in which the HaMuSV transforming gene (Ha-v-ras) is expressed from the mouse mammary tumor virus (MMTV) promoter increases the ability of the MMTV v-ras chimeras to transform mouse fibroblasts in culture 50- to 100-fold. Significant stimulation of transfection efficiency occurs only when glucocorticoids are present in the culture medium. Glucocorticoids also elevate the steady-state concentration of MMTV-initiated v-ras mRNA in cell lines isolated from these transfections, and MMTV-v-ras fusion transcripts are initiated at the normal MMTV cap site; potential cryptic initiation events associated with the enhancer could not be detected. The ability of the enhancer to increase the transcriptional activity of the MMTV promoter was also studied in acute transfection assays where expression of the chloramphenical acetyl transferase (CAT) gene is driven by the MMTV promoter. In this system the strong positive effect on MMTV transcription is again obtained only when the cells are hormone treated. These experiments indicate that the hormone-regulatory region is capable of modulating the function of an exogenously introduced enhancer element.

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Selected References

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  1. Banerji J., Olson L., Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983 Jul;33(3):729–740. doi: 10.1016/0092-8674(83)90015-6. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Benoist C., Chambon P. In vivo sequence requirements of the SV40 early promotor region. Nature. 1981 Mar 26;290(5804):304–310. doi: 10.1038/290304a0. [DOI] [PubMed] [Google Scholar]
  4. Berg P. E., Yu J. K., Popovic Z., Schumperli D., Johansen H., Rosenberg M., Anderson W. F. Differential activation of the mouse beta-globin promoter by enhancers. Mol Cell Biol. 1983 Jul;3(7):1246–1254. doi: 10.1128/mcb.3.7.1246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Buetti E., Diggelmann H. Glucocorticoid regulation of mouse mammary tumor virus: identification of a short essential DNA region. EMBO J. 1983;2(8):1423–1429. doi: 10.1002/j.1460-2075.1983.tb01601.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chandler V. L., Maler B. A., Yamamoto K. R. DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter hormone responsive in vivo. Cell. 1983 Jun;33(2):489–499. doi: 10.1016/0092-8674(83)90430-0. [DOI] [PubMed] [Google Scholar]
  8. Corden J., Wasylyk B., Buchwalder A., Sassone-Corsi P., Kedinger C., Chambon P. Promoter sequences of eukaryotic protein-coding genes. Science. 1980 Sep 19;209(4463):1406–1414. doi: 10.1126/science.6251548. [DOI] [PubMed] [Google Scholar]
  9. Dhar R., Ellis R. W., Shih T. Y., Oroszlan S., Shapiro B., Maizel J., Lowy D., Scolnick E. Nucleotide sequence of the p21 transforming protein of Harvey murine sarcoma virus. Science. 1982 Sep 3;217(4563):934–936. doi: 10.1126/science.6287572. [DOI] [PubMed] [Google Scholar]
  10. Dhar R., McClements W. L., Enquist L. W., Vande Woude G. F. Nucleotide sequences of integrated Moloney sarcoma provirus long terminal repeats and their host and viral junctions. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3937–3941. doi: 10.1073/pnas.77.7.3937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Donehower L. A., Huang A. L., Hager G. L. Regulatory and coding potential of the mouse mammary tumor virus long terminal redundancy. J Virol. 1981 Jan;37(1):226–238. doi: 10.1128/jvi.37.1.226-238.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gillies S. D., Morrison S. L., Oi V. T., Tonegawa S. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell. 1983 Jul;33(3):717–728. doi: 10.1016/0092-8674(83)90014-4. [DOI] [PubMed] [Google Scholar]
  13. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Govindan M. V., Spiess E., Majors J. Purified glucocorticoid receptor-hormone complex from rat liver cytosol binds specifically to cloned mouse mammary tumor virus long terminal repeats in vitro. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5157–5161. doi: 10.1073/pnas.79.17.5157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gross-Bellard M., Oudet P., Chambon P. Isolation of high-molecular-weight DNA from mammalian cells. Eur J Biochem. 1973 Jul 2;36(1):32–38. doi: 10.1111/j.1432-1033.1973.tb02881.x. [DOI] [PubMed] [Google Scholar]
  16. Hager G. L., Chang E. H., Chan H. W., Garon C. F., Israel M. A., Martin M. A., Scolnick E. M., Lowy D. R. Molecular cloning of the Harvey sarcoma virus closed circular DNA intermediates: initial structural and biological characterization. J Virol. 1979 Sep;31(3):795–809. doi: 10.1128/jvi.31.3.795-809.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Huang A. L., Ostrowski M. C., Berard D., Hager G. L. Glucocorticoid regulation of the Ha-MuSV p21 gene conferred by sequences from mouse mammary tumor virus. Cell. 1981 Dec;27(2 Pt 1):245–255. doi: 10.1016/0092-8674(81)90408-6. [DOI] [PubMed] [Google Scholar]
  18. Hynes N., van Ooyen A. J., Kennedy N., Herrlich P., Ponta H., Groner B. Subfragments of the large terminal repeat cause glucocorticoid-responsive expression of mouse mammary tumor virus and of an adjacent gene. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3637–3641. doi: 10.1073/pnas.80.12.3637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jainchill J. L., Aaronson S. A., Todaro G. J. Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells. J Virol. 1969 Nov;4(5):549–553. doi: 10.1128/jvi.4.5.549-553.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Laimins L. A., Khoury G., Gorman C., Howard B., Gruss P. Host-specific activation of transcription by tandem repeats from simian virus 40 and Moloney murine sarcoma virus. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6453–6457. doi: 10.1073/pnas.79.21.6453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lee F., Mulligan R., Berg P., Ringold G. Glucocorticoids regulate expression of dihydrofolate reductase cDNA in mouse mammary tumour virus chimaeric plasmids. Nature. 1981 Nov 19;294(5838):228–232. doi: 10.1038/294228a0. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Luciw P. A., Bishop J. M., Varmus H. E., Capecchi M. R. Location and function of retroviral and SV40 sequences that enhance biochemical transformation after microinjection of DNA. Cell. 1983 Jul;33(3):705–716. doi: 10.1016/0092-8674(83)90013-2. [DOI] [PubMed] [Google Scholar]
  24. Majors J., Varmus H. E. A small region of the mouse mammary tumor virus long terminal repeat confers glucocorticoid hormone regulation on a linked heterologous gene. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5866–5870. doi: 10.1073/pnas.80.19.5866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Myers R. M., Rio D. C., Robbins A. K., Tjian R. SV40 gene expression is modulated by the cooperative binding of T antigen to DNA. Cell. 1981 Aug;25(2):373–384. doi: 10.1016/0092-8674(81)90056-8. [DOI] [PubMed] [Google Scholar]
  27. Ostrowski M. C., Berard D., Hager G. L. Specific transcriptional initiation in vitro on murine type C retrovirus promoters. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4485–4489. doi: 10.1073/pnas.78.7.4485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Parks W. P., Hubbell E. S., Goldberg R. J., O'Neill F. J., Scolnick E. M. High frequency variation in mammary tumor virus expression in cell culture. Cell. 1976 May;8(1):87–93. doi: 10.1016/0092-8674(76)90189-6. [DOI] [PubMed] [Google Scholar]
  29. Payvar F., DeFranco D., Firestone G. L., Edgar B., Wrange O., Okret S., Gustafsson J. A., Yamamoto K. R. Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region. Cell. 1983 Dec;35(2 Pt 1):381–392. doi: 10.1016/0092-8674(83)90171-x. [DOI] [PubMed] [Google Scholar]
  30. Payvar F., Firestone G. L., Ross S. R., Chandler V. L., Wrange O., Carlstedt-Duke J., Gustafsson J. A., Yamamoto K. R. Multiple specific binding sites for purified glucocorticoid receptors on mammary tumor virus DNA. J Cell Biochem. 1982;19(3):241–247. doi: 10.1002/jcb.240190305. [DOI] [PubMed] [Google Scholar]
  31. Perucho M., Hanahan D., Wigler M. Genetic and physical linkage of exogenous sequences in transformed cells. Cell. 1980 Nov;22(1 Pt 1):309–317. doi: 10.1016/0092-8674(80)90178-6. [DOI] [PubMed] [Google Scholar]
  32. Pfahl M. Specific binding of the glucocorticoid-receptor complex to the mouse mammary tumor proviral promoter region. Cell. 1982 Dec;31(2 Pt 1):475–482. doi: 10.1016/0092-8674(82)90140-4. [DOI] [PubMed] [Google Scholar]
  33. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  34. Ringold G. M., Shank P. R., Varmus H. E., Ring J., Yamamoto K. R. Integration and transcription of mouse mammary tumor virus DNA in rat hepatoma cells. Proc Natl Acad Sci U S A. 1979 Feb;76(2):665–669. doi: 10.1073/pnas.76.2.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Scheidereit C., Geisse S., Westphal H. M., Beato M. The glucocorticoid receptor binds to defined nucleotide sequences near the promoter of mouse mammary tumour virus. Nature. 1983 Aug 25;304(5928):749–752. doi: 10.1038/304749a0. [DOI] [PubMed] [Google Scholar]
  36. Sekikawa K., Levine A. J. Isolation and characterization of polyoma host range mutants that replicate in nullipotential embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1100–1104. doi: 10.1073/pnas.78.2.1100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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]
  38. Thompson E. B., Granner D. K., Gelehrter T., Erickson J., Hager G. L. Unlinked control of multiple glucocorticoid-induced processes in HTC cells. Mol Cell Endocrinol. 1979 Sep;15(3):135–150. doi: 10.1016/0303-7207(79)90034-0. [DOI] [PubMed] [Google Scholar]
  39. Ucker D. S., Ross S. R., Yamamoto K. R. Mammary tumor virus DNA contains sequences required for its hormone-regulated transcription. Cell. 1981 Dec;27(2 Pt 1):257–266. doi: 10.1016/0092-8674(81)90409-8. [DOI] [PubMed] [Google Scholar]
  40. Wasylyk B., Wasylyk C., Augereau P., Chambon P. The SV40 72 bp repeat preferentially potentiates transcription starting from proximal natural or substitute promoter elements. Cell. 1983 Feb;32(2):503–514. doi: 10.1016/0092-8674(83)90470-1. [DOI] [PubMed] [Google Scholar]
  41. Young H. A., Shih T. Y., Scolnick E. M., Parks W. P. Steroid induction of mouse mammary tumor virus: effect upon synthesis and degradation of viral RNA. J Virol. 1977 Jan;21(1):139–146. doi: 10.1128/jvi.21.1.139-146.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]

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