Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Cell-type-specific contacts to immunoglobulin enhancers in nuclei

Nature volume 313, pages 798–801 (1985)Cite this article

Abstract

The introns separating the variable and constant regions of active immunoglobulin genes contain tissue-specific transcriptional enhancer elements1–3, DNA segments which act in cis in an orientation and distanceindependent (up to a few kilobases (kb)) manner to enhance transcription initiation at adjacent promoters4–9. The immunoglobulin heavy-chain enhancer is active only in lymphoid cells: in transfection assays it is capable of controlling in cis transcription from the simian virus 40 (SV40) T-antigen, rabbit β-globin and immunoglobulin gene promoters up to at least 2 kb away1–3. Genetic deletion analysis suggests that a region of as few as 140 base pairs (bp) is sufficient for the enhancement effect1,2. These functional characteristics and DNA sequences are conserved between mouse and man10–15. However, it is riot known whether tissue-specific proteins bind to the enhancer. Proteins that interact with DNA at specific sequences can prevent or enhance the reactions of individual guanines or adenines with dimethyl sulphate (DMS)16, and this property has been used to display the DNA contacts of various regulatory proteins16–26. Here we apply this DMS strategy in experiments involving single-copy genes within intact mammalian nuclei using genomic sequencing27.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Gillies, S. D., Morrison, S. L., Oi, V. T. & Tonegawa, S. Cell 33, 717–728 (1983).

    Article  CAS  Google Scholar 

  2. Banergi, J., Olson, L. & Schaffner, W. Cell 33, 729–740 (1983).

    Article  Google Scholar 

  3. Neuberger, M. S. EMBO J. 2, 1373–1378 (1983).

    Article  CAS  Google Scholar 

  4. Benoist, C. & Chambon, P. Nature 290, 304–310 (1981).

    Article  ADS  CAS  Google Scholar 

  5. de Villiers, J. & Schaffner, W. Nucleic Acids Res. 9, 6251–6264 (1981).

    Article  CAS  Google Scholar 

  6. Gruss, P., Dhar, R. & Khoury, G. Proc. natn. Acad. Sci. U.S.A. 8, 943–947 (1981).

    Article  ADS  Google Scholar 

  7. Moreau, P. et al. Nucleic Acids Res. 9, 6047–6068 (1981).

    Article  ADS  CAS  Google Scholar 

  8. Wasylyk, B., Wasylyk, C., Augereau, P. & Chambon, P. Cell 32, 503–514 (1983).

    Article  CAS  Google Scholar 

  9. Banerji, J., Rusconi, S. & Schaffner, W. Cell 27, 299–308 (1981).

    Article  CAS  Google Scholar 

  10. Picard, D. & Schaffner, W. Nature 307, 80–82 (1984).

    Article  ADS  CAS  Google Scholar 

  11. Emorine, L., Kuehl, M., Weir, L., Leder, P. & Max, E. E. Nature 304, 447–449 (1983).

    Article  ADS  CAS  Google Scholar 

  12. Rabbits, T. H., Forster, A., Baer, R. & Hamlyn, P. H. Nature 306, 806–809 (1983).

    Article  ADS  Google Scholar 

  13. Hayday, A. et al. Nature 307, 334–340 (1984).

    Article  ADS  CAS  Google Scholar 

  14. Mills, F. C., Fisher, L. M., Kuroda, R., Ford, A. M. & Gould, H. J. Nature 306, 809–812 (1983).

    Article  ADS  CAS  Google Scholar 

  15. Chung, S.-Y., Folsom, V. & Wooley, J. Proc. natn. Acad. Sci. U.S.A. 80, 2427–2431 (1983).

    Article  ADS  CAS  Google Scholar 

  16. Gilbert, W., Maxam, A. & Mirzabekov, A. Alfred Benzon Symp. 9, 139–148 (Munksgaard, Copenhagen, 1976).

    CAS  Google Scholar 

  17. Johnson, A. D. et al. Nature 294, 217–223 (1981).

    Article  ADS  CAS  Google Scholar 

  18. Taniguchi, T., O'Neill, M. & De Crombrugghe, B. Proc. natn. Acad. Sci. U.S.A. 76, 5090–5094 (1979).

    Article  ADS  CAS  Google Scholar 

  19. Siebenlist, U., Simpson, R. B. & Gilbert, W. Cell 20, 269–281 (1980).

    Article  CAS  Google Scholar 

  20. Johnsrud, L. Proc. natn. Acad. Sci. U.S.A. 75, 5314–5318 (1978).

    Article  ADS  CAS  Google Scholar 

  21. Lu, A.-L., Jack, W. E. & Modrich, P. J. biol. Chem. 256, 13200–13206 (1981).

    CAS  PubMed  Google Scholar 

  22. Germino, J. & Bastia, D. Cell 34, 124–134 (1983).

    Article  Google Scholar 

  23. Brent, R. & Ptashne, M. Proc. natn. Acad. Sci. U.S.A. 78, 4204–4208 (1981).

    Article  ADS  CAS  Google Scholar 

  24. Kirkegaard, K. & Wang, J. Cell 23, 721–729 (1981).

    Article  CAS  Google Scholar 

  25. Karin, M. et al. Nature 308, 513–519 (1984).

    Article  ADS  CAS  Google Scholar 

  26. Myers, R. M., Rio, D. C., Robbins, A. K. & Tjian, R. Cell 25, 373–384 (1981).

    Article  CAS  Google Scholar 

  27. Church, G. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 81, 1991–1995 (1984).

    Article  ADS  CAS  Google Scholar 

  28. Wigler, M. et al. Proc. natn. Acad. Sci. U.S.A. 76, 1373–1376 (1979).

    Article  ADS  CAS  Google Scholar 

  29. Gerondakis, S., Cory, S. & Adams, J. M. Cell 36, 973–998 (1984).

    Article  CAS  Google Scholar 

  30. Kemp, D. J., Harris, A. W., Cory, S. & Adams, J. M. Proc. natn. Acad. Sci. U.S.A. 77, 2876–2880 (1980).

    Article  ADS  CAS  Google Scholar 

  31. Volloch, V. & Housman, D. J. Cell Biol. 93, 390 (1982).

    Article  CAS  Google Scholar 

  32. McIntire, K. R., Asofsky, R. M., Potter, M. & Kuff, E. L. Science 150, 361–363 (1965).

    Article  ADS  CAS  Google Scholar 

  33. Maxam, A. M. & Gilbert, W. Meth. Enzym. 65, 497–560 (1980).

    Article  Google Scholar 

  34. Rubin, C. M. & Schmid, C. W. Nucleic Acids Res. 8, 4613–4619 (1980).

    Article  CAS  Google Scholar 

  35. Herr, W., Corbin, V. & Gilbert, W. Nucleic Acids Res. 10, 6931–6944 (1983).

    Article  Google Scholar 

  36. Ephrussi, A., Church, G., Tonegawa, S. & Gilbert, W. Science 227, 134–140 (1985).

    Article  ADS  CAS  Google Scholar 

  37. Emorine, L. & Max, E. E. Nucleic Acids Res. 11, 8877–8890 (1983).

    Article  CAS  Google Scholar 

  38. Weiher, H., Konig, M. & Gruss, P. Science 219, 626–631 (1983).

    Article  ADS  CAS  Google Scholar 

  39. Reddy, V. B. et al. Science 200, 494–502 (1978).

    Article  ADS  CAS  Google Scholar 

  40. Fiers, W. et al. Nature 273, 113–119 (1978).

    Article  ADS  CAS  Google Scholar 

  41. Sutcliffe, J. G. Cold Spring Hrb. Symp. quant. Biol. 43, 77–90 (1978).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy, University of California, San Francisco, California, 94143, USA

    George M. Church

  2. Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    Anne Ephrussi & Susumu Tonegawa

  3. Biogen Research Corporation, 14 Cambridge Center, Cambridge, Massachusetts, 02142, USA

    Walter Gilbert

Authors
  1. George M. Church
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne Ephrussi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Walter Gilbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susumu Tonegawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Church, G., Ephrussi, A., Gilbert, W. et al. Cell-type-specific contacts to immunoglobulin enhancers in nuclei. Nature 313, 798–801 (1985). https://doi.org/10.1038/313798a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/313798a0

This article is cited by

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.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing