Abstract
Proteins binding to specific regions of DNA with high affinity frequently govern or regulate reactions at the gene level1–8. We have identified a high-affinity binding site in the immunoglobulin μ gene that binds a specific nuclear protein, and have now characterized it fully using nuclear factor 1 (NF-1), a protein purified from the nuclei of HeLa cells9,10 and required for the in vitro replication of adenovirus (Ad) DNA9–12. NF-1 protects a 25-base pair (bp) double-stranded segment of DNA which shares a consensus sequence, 5′ TGGA/CNNNNNGCCAA 3′, with similar binding sites in the Ad-5 terminal repeat10–12 and the human c-myc gene13. Although this site differs from the enhancer region13–16, a biological function is suggested by the fact that it is DNase I hypersensitive in immunoglobulin-producing lymphoblastoid cells. The binding site for the NF-1 protein in the μ gene, by analogy with the site in the Ad-5 terminal repeat, may represent one component of a cellular origin of replication; alternatively, it may be responsible for the activation of the chromatin in this region.
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Gilbert, W., Maizels, N. & Maxam, A. Cold Spring Harb. Symp. quant. Biol. 38, 845–855 (1974).
Maniatis, T. et al. Cell 5, 109–113 (1975).
Dynan, W. S. & Tjian, R. Cell 35, 79–87 (1983).
Jones, K. A. & Tjian, R. Cell 36, 155–162 (1984).
Compton, J. G., Schrader, W. T. & O'Malley, B. W. Proc. nat. Acad. Sci. U.S.A. 80, 16–20 (1983).
Karin, M. et al. Nature 308, 513–519 (1984).
Renkawitz, R., Schutz, G. von der Ahe, D. & Beato, M. Cell 37, 503–510 (1984).
Chandler, V. L., Maler, B. A. & Yamamoto, K. R. Cell 33, 489–499 (1983).
Nagata, K., Guggenheimer, R. A., Enomoto, T., Lichy, J. H. & Hurwitz, J. Proc. natn. Acad. Sci. U.S.A. 79, 6438–6442 (1982).
Rawlins, D. R., Rosenfeld, P. J., Wides, R. J., Challberg, M. D. & Kelly, T. J. Jr Cell 37, 309–319 (1984).
Nagata, K., Guggenheimer, R. A. & Hurwitz, J. Proc. natn. Acad. Sci. U.S.A. 80, 6177–6181 (1983).
Guggenheimer, R. A., Stillman, B. W., Nagata, K., Tamanoi, F. & Hurwitz, J. Proc. natn. Acad. Sci. U.S.A. 81, 3069–3073 (1984).
Siebenlist, U., Hennighausen, L., Battey, J. & Leder, P. Cell 37, 381–391 (1984).
Hayday, A. et al. Nature 307, 334–340 (1984).
Rabbitts, T. H., Hamlyn, P. H. & Baer, R. Nature 306, 760–765 (1983).
Bannerji, J., Olson, L. & Schaffner, W. Cell 33, 729–740 (1983).
Taub, R. et al. Proc. natn. Acad. Sci. U.S.A. 79, 7837–7841 (1982).
Leder, P. et al. Science 222, 765–771 (1983).
Battey, J. et al. Cell 34, 779–789 (1983).
Taub, R. et al. Cell 36, 339–348 (1984).
Riggs, A. D., Bourgeois, S. & Cohn, M. J. molec. Biol. 53, 401–417 (1970).
Jack, R. S., Gehring, W. J. & Brack, C. Cell 24, 321–333 (1981).
Borgmeyer, U., Nowock, J. & Sippel, A. E. Nucleic Acids Res. 12, 4295–4311 (1984).
Pabo, C. & Lewis, A. Nature 298, 443–447 (1982).
Shermoen, A. W. & Beckendorf, S. K. Cell 29, 601–607 (1982).
Emerson, B. M. & Felsenfeld, G. Proc. natn. Acad. Sci. U.S.A. 81, 95–99 (1984).
Gronostajski, R. M., Nagata, K. & Hurwitz, J. Proc. natn. Acad. Sci. U.S.A. 81, 4013–4017 (1984).
Lewin, B. M. Gene Expression 2 2nd edn (Wiley, New York, 1980).
Leder, P. Sci. Am. 246(5), 102–115 (1982).
Shimizu, A. & Honjo, T. Cell 36, 801–803 (1984).
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Hennighausen, L., Siebenlist, U., Danner, D. et al. High-affinity binding site for a specific nuclear protein in the human IgM gene. Nature 314, 289–292 (1985). https://doi.org/10.1038/314289a0
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DOI: https://doi.org/10.1038/314289a0
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