Abstract
Enhancers are cis-act ing control elements which can stimulate at a distance the activity of a variety of eukaryotic promoters. First identified as a repeated 72 base pair (bp) sequence upstream of the simian virus 40 (SV40) early gene promoter1–5, enhancers have since been shown to be associated with numerous other viral6 and cellular7–13 genes. Although there are no strong homologies between the sequences of different enhancers, a number of short and degenerate consensus sequences have been identified, including the ‘core’ element GTGGA/TA/TA/TG (refs 14, 15) and stretches of alternating purines and pyrimidines which may have the potential to form left-handed Z DNA16. To study the functional significance of two alternating purine and pyrimidine sequences in the SV40 enhancer, we have introduced various combinations of point mutations into a modified SV40 enhancer which contained only one copy of the 72 bp element (W.H., Y.G., A. Nordheim and A. Rich, unpublished results); one of these combinations impaired both the activity of the enhancer and growth of SV40. We describe here the structure of 18 revertants of this mutant and suggest that in each of the 18 revertants, the defects of the original mutant have been overcome by simple tandem duplications in the enhancer region, all of which include the ‘core’ element.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Banerji, J., Rusconi, S. & Schaffner, W. Cell 27, 299–308 (1981).
Moreau, P. et al. Nucleic Acids Res. 9, 6047–6068 (1981).
Gruss, P., Dhar, R. & Khoury, G. Proc. natn. Acad. Sci. U.S.A. 78, 943–947 (1981).
Benoist, C. & Chambon, P. Nature 290, 304–310 (1981).
Fromm, M. & Berg, P. J. molec. appl. Genet. 1, 457–481 (1982).
Gluzman, Y. & Shenk, T. (eds) Enhancers and Eukaryotic gene expression. (Cold Spring Harbor Laboratory, New York, 1983).
Banerji, J., Olson, L. & Schaffner, W. Cell 33, 729–740 (1983).
Gillies, S. D., Morrison, S. L., Oi, V. T. & Tonegawa, S. Cell 33, 717–728 (1983).
Neuberger, M. S. EMBO J. 2, 1373–1378 (1983).
Queen, C. & Baltimore, D. Cell 33, 741–748 (1983).
Picard, D. & Schaffner, W. Nature 307, 80–82 (1984).
Walker, M. D., Edlund, T., Boulet, A. M. & Rutter, W. J. Nature 306, 557–561 (1983).
Gillies, S. D., Folsom, V. & Tonegawa, S. Nature 310, 594–597 (1984).
Laimins, L. A., Khoury, G., Gorman, C., Howard, B. & Gruss, P. Proc. natn. Acad. Sci. U.S.A. 79, 6453–6457 (1982).
Weiher, H., Konig, M. & Gruss, P. Science 219, 626–631 (1983).
Nordheim, A. & Rich, A. Nature 303, 674–679 (1983).
Weber, F., de Villiers, J. & Schaffner, W. Cell 36, 983–992.
Swimmer, C. & Shenk, T. Proc. natn. Acad. Sci. U.S.A. 81, 6652–6656 (1984).
Rosenthal, N., Kress, M., Gruss, P. & Khoury, G. Science 222, 749–755 (1983).
Ruley, H. E. & Fried, M. J. Virol. 47, 233–237 (1983).
Fujimura, F. K., Deininger, P. L., Friedmann, T. & Linney, E. Cell 23, 809–814 (1981).
Sekikawa, K. & Levine, A. J. Proc. natn. Acad. Sci U.S.A. 78, 1100–1104 (1981).
Katinka, M., Yaniv, M., Vasseur, M. & Blangy, D. Cell 20, 393–399 (1980).
Weiss, R., Teich, N., Varmus, H. & Coffin, J. RNA Tumour Viruses, (Cold Spring Harbor Laboratory, New York, (1982).
Lusky, M., Berg, L., Weiher, H. & Botchan, M. Molec. Cell Biol. 3, 1108–1122 (1983).
Lavi, S. & Winocour, E. J. Virol. 9, 309–316 (1972).
Tai, H. T., Smith, C. A., Sharp, P. A. & Vinograd, J. J. Virol. 9, 317–325 (1972).
Martin, M. A., Gelb, L. D., Fareed, G. C. & Milstein, J. B. J. Virol. 12, 748–757 (1973).
Reddy, V. B. et al. Science 200, 494–502 (1978).
Ghosh, P. K. et al. Proc. natn. Acad. Sci. U.S.A. 78, 1386–1390 (1981).
Been, M. D., Burgess, R. R. & Champoux, J. J. Nucleic Adds Res. 12, 3097–3114 (1984).
Tooze, J. (ed.) DNA Tumor Viruses. (Cold Spring Harbor Laboratory, New York, (1981).
Zoller, M. J. & Smith, M. Nucleic Acids Res. 10, 6487–6500 (1982).
Gluzman, Y. & Ahrens, B. Virology 123, 78–92 (1982).
McCutchan, J. H. & Pagano, J. S. J. natn. Cancer Inst. 41, 351–357 (1968).
Hirt, B. J. molec. Biol. 26, 365–369 (1967).
Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).
Biggin, M. D., Gibson, T. J. & Hong, G. F. Proc. natn. Acad. Sci. U.S.A 80, 3963–3965 (1983).
Messing, J. & Vieira, J. Gene 19, 269–276 (1982).
Treisman, R., Green, M. R. & Maniatis, T. Proc. natn. Acad. Sci. U.S.A. 80, 7428–7432 (1983).
de Villiers, J. & Schaffner, W. Nucleic Acids Res. 9, 6251–6264 (1981).
Ish-Horowitz, D. & Burke, J. F. Nucleic Acids Res. 9, 2989–2998 (1981).
Berk, A. J. & Sharp, P. A. Cell 12, 721–732 (1977).
Zinn, K., DiMaio, D. & Maniatis, T. Cell 34, 865–879 (1983).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Herr, W., Gluzman, Y. Duplications of a mutated simian virus 40 enhancer restore its activity. Nature 313, 711–714 (1985). https://doi.org/10.1038/313711a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/313711a0
This article is cited by
-
Epigenetic Thpok silencing limits the time window to choose CD4+ helper-lineage fate in the thymus
The EMBO Journal (2013)
-
Enhancer binding factors AP-4 and AP-1 act in concert to activate SV40 late transcription in vitro
Nature (1988)
-
The SV40 enhancer contains two distinct levels of organization
Nature (1988)
-
Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40
Nature (1987)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
