Abstract
Heavy chain immunoglobulin gene expression requires two independent DNA recombination systems1–3. The first DNA rearrangement event (V–D–J recombination) involves the formation of a complete variable region (VH) gene in pre-B lymphocytes3–6. The second series of recombination events allows for a switch in heavy chain constant region class from μ to either γ3, γ1, γ2b, γ2a, ɛ or α1–3. These recombination events occur in intervening sequences but do not alter or generate new coding information which is a common feature of V–D–J unions1–3. Tandemly repeated DNA sequences, spanning ∼2–5 kilobases (b), are localized ∼1.5 kilobase pairs 5′ of each CH gene and have been termed CH switch (S) regions.2,7. Two short, simple sequences that are shared by all switch region repeats (GAGCT and GGGGT) have been proposed to facilitate CH switching by homologous DNA recombination8. Unlike other switch regions, a large portion of the Sμ region (3 kb) consists of essentially pure tandem repeats of GAGCT which are occasionally interrupted by a GGGGT8. However, the precise sites of switch-recombination in Sμ are generally located considerably 5′ of this genetically unstable stretch9,10 of GAGCT repeats (Fig. 1). We now report the properties of a novel CH S region sequence, YAGGTTG, which is 5′ of switch recombination sites and preferentially repeated in S regions.
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References
Davis, M. M. et al. Nature 283, 733–739 (1980).
Kataoka, T., Kawakami, T., Takahashi, N. & Honjo, T. Proc. natn. Acad. Sci. U.S.A. 77, 919–923 (1980).
Sakano, H., Maki, R., Kurosawa, Y., Roeder, W. & Tonegawa, S. Nature 286, 676–683 (1980).
Early, P., Huang, H., Davis, M., Calame, K. & Hood, L. Cell 19, 981–992 (1980).
Matthyssens, G. & Rabbitts, T. H. Proc. natn. Acad. Sci. U.S.A. 77, 6561–6565 (1980).
Siebenlist, U., Ravetch, J. U., Korsmeyer, S., Waldmann, T. & Leder, P. Nature 294, 631–635 (1981).
Davis, M. M., Kim, S. K. & Hood, L. Science 209, 1360–1365 (1980).
Nikaido, T., Nakai, S. & Honjo, T. Nature 292, 845–848 (1981).
Marcu, K. B., Banerji, J., Penncavage, N. A., Lang, R. & Arnheim, N. Cell 22, 187–196 (1980a).
Marcu, K. B. et al. Cold Spring Harb. Symp. quant. Biol. 45, 899–911 (1980).
Kataoka, T., Miyata, T. & Honjo, T. Cell 23, 357–368 (1981).
Hood, L. et al. Cold Spring Harb. Symp. quant. Biol. 45, 887–898 (1980).
Dunnick, W., Rabbitts, T. H. & Milstein, C. Nature 286, 669–675 (1980).
Takahashi, N., Kataoka, T. & Honjo, T. Gene 11, 117–127 (1980).
Konkel, D. A., Maizel, J. V. & Leder, P. Cell 18, 865–873 (1979).
Nishioka, Y. & Leder, P. Cell 18, 875–882 (1979).
Sakano, H., Huppi, K., Heinrich, G. & Tonegawa, S. Nature 280, 288–294 (1979).
Leder, P. et al. Cold Spring Harb. Symp. quant. Biol. 45, 859–865 (1980).
Morrison, S. L. in Cells of Immunoglobulin Synthesis (eds Pernis, B. & Vogel, H. J.) 113–126 (Academic, New York, 1979).
Franklin, E. C., Frangione, B. & Buxbaum, J. in Cells of Immunoglobulin Synthesis (eds Pernis, B. & Vogel, H. J.) 89–95 (Academic, New York, 1979).
Takahashi, N., Nikai, S. & Honjo, T. Nucleic Acids. Res. 8, 5983–5991 (1980).
Ravetch, J. V., Kirsch, I. R. & Leder, P. Proc. natn. Acad. Sci. U.S.A. 77, 6734–6738 (1980).
Rabbitts, T. H., Forster, A. and Milstein, C. P. Nucleic Acids Res. 9, 4509–4524 (1981).
Seidman, J. G. & Leder, P. Nature 286, 779–783 (1980).
Kenter, A. L., Eckhardt, L. A., Tilley, S. A., Birshtein, B. K. in Immunoglobulin Idiotypes and Their Expression, ICN-UCLA Symp. molec. cell. Biol. (eds Janeway, C., Sercarz, E. E., Wigzell, H. & Fox, C. F.) (Academic, New York, in the press).
Eckhardt, L. A., Tilley, S. A., Lang, R. B., Marcu, K. B. & Birshtein, B. K. Proc. natn. Acad. Sci. U.S.A. 79, 3006–3010 (1982).
Stanton, L. W. & Marcu, K. B. Nucleic Acids Res. (submitted).
Kawakami, T., Takahashi, N. & Honjo, T. Nucleic Acids. Res. 8, 3933–3945 (1980).
Honjo, T. et al. Cell 18, 559–568 (1979).
Tucker, P. W., Marcu, K. B., Newell, N., Richards, J. & Blattner, F. R. Science 206, 1301–1306 (1979).
Yamawaki-Kataoka, Y., Kataoka, T., Takahashi, N., Obata, M. & Honjo, T. Nature 283, 786–789 (1980).
Ollo, R., Auffray, C., Morchamps, C. & Rougeon, F. Proc. natn. Acad. Sci. U.S.A. 78, 2442–2446 (1981).
Tucker, P. W., Slightom, J. L. & Blattner, F. R. Proc. natn. Acad. Sci. U.S.A. 78, 7684–7688 (1981).
Kim, S., Davis, M. M., Sinn, E., Patten, P. & Hood, L. Cell 27, 573–581 (1981).
Obata, M. et al. Proc. natn. Acad. Sci. U.S.A. 78, 2437–2441 (1981).
Lang, R. B., Stanton, L. W. & Marcu, K. B. Nucleic Acids Res. 10, 611–630 (1982).
Kirsch, I. R. et al. Nature 293, 585–587 (1981).
Harris, L. J., Lang, R. B. & Marcu, K. B. Proc. natn. Acad. Sci. U.S.A. 79 (in the press).
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Marcu, K., Lang, R., Stanton, L. et al. A model for the molecular requirements of immunoglobulin heavy chain class switching. Nature 298, 87–89 (1982). https://doi.org/10.1038/298087a0
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DOI: https://doi.org/10.1038/298087a0
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