Skip to main content
SpringerLink
Log in

DNA binding factors for the CpG-rich island containing the promoter of the human X-linkedPGK gene

  • Published:
Somatic Cell and Molecular Genetics

Abstract

The gene coding for the glycolytic enzyme phosphoglycerate kinase (PGK-1) is X-linked in mammals and has a G+C-rich 5′ region characteristic of several constitutive genes. Despite the fact that PGK-1 is constitutively expressed, it is transcriptionally regulated in female cells by X chromosome inactivation. To study the expression and regulation of the PGK-1 gene, we have analyzed the binding of transacting factors to the 5′ region of the PGK-1 gene. We detect at least three distinct binding activities that interact in a sequence-specific manner in vitro with at least six different sites in the 5′ region. Two of these binding activities generate DNase I-protected footprints centered approximately 360 bp and 130 bp upstream of the transcription start point. We have examined the promoter specificity of the three binding activities in gel mobility-shift assays by competition with cloned promoter fragments of other genes. None of the binding activities interacts exclusively with X-linked promoters. However, one activity binds preferentially to G+C-rich promoters, and another activity appears to bind preferentially to only two of the promoters tested. Previous studies have demonstrated that one HpaII/MspI site, which is included within a footprinted region observed in this study, is fully methylated in the inactive X chromosome and totally unmethylated on the active X chromosome. Competition studies using synthetic oligonucleotides containing 5-methylcytosine at all CpG sites in this region demonstrate that DNA methylation does not significantly alter the affinity between the corresponding binding activity and this binding site.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Literature cited

  1. Bird, A.P. (1986).Nature 321:209–213.

    PubMed  Google Scholar 

  2. Singer-Sam, J., Keith, D.H., Tani, K., Simmer, R.L., Shively, L., Lindsay, S., Yoshida, A., and Riggs, A.D. (1984).Gene 32:409–417.

    PubMed  Google Scholar 

  3. Conklin, K.F., Groudine, M. (1984). InDNA Methylation, (eds.) Razin, A., Cedar, H., and Riggs, A.D. (Springer-Verlag, New York), pp. 293–351.

    Google Scholar 

  4. Martini, G., Toniolo, D., Vulliamy, T., Luzzatto, L., Dono, R., Viglietto, G., Paonessa, G., D'Urso, M., and Persico, M.G. (1986).EMBO J. 5:1849–1855.

    PubMed  Google Scholar 

  5. Monk, M. (1986).Bioessays 4:204–208.

    PubMed  Google Scholar 

  6. Chapman, V.M., Kratzer, P.G., Siracusa, L.O., Quarantillo, B.A., Evans, R., and Liskay, R.M. (1982).Proc. Natl. Acad. Sci. U.S.A. 79:5357–5361.

    PubMed  Google Scholar 

  7. Kratzer, P.G., Chapman, V.M., Lambert, H., Evans, R., and Liskay, R.M. (1983).Cell 33:37–42.

    PubMed  Google Scholar 

  8. Liskay, R.M., and Evans, R. (1980).Proc. Natl. Acad. Sci. U.S.A. 77:4895–4898.

    PubMed  Google Scholar 

  9. Venolia, L., and Gartler, S.M. (1983).Nature 302:82–83.

    PubMed  Google Scholar 

  10. Graves, J.A.M. (1982).Exp. Cell. Res. 141:99–105.

    PubMed  Google Scholar 

  11. Lester, S.C., Korn, N.J., and DeMars, R. (1982).Somat. Cell Genet. 8:265–284.

    PubMed  Google Scholar 

  12. Mohandas, T., Sparkes, R.S., and Shapiro, L.J. (1981).Science 211:393–396.

    PubMed  Google Scholar 

  13. Venolia, L., Gartler, S.M., Wasserman, E.R., Yen, P., Mohandas, T., and Shapiro, L.J. (1982).Proc. Natl. Acad. Sci. U.S.A. 79:2352–2354.

    PubMed  Google Scholar 

  14. Keith, D.H., Singer-Sam, J., and Riggs, A.D. (1986).Mol. Cell. Biol. 6:4122–4125.

    PubMed  Google Scholar 

  15. Wolfe, S.F., Dintzis, S., Toniolo, D., Persico, G., Lunnen, K.D., Axelman, J., and Migeon, B.R. (1984).Nucleic Acids Res. 12:9333–9348.

    PubMed  Google Scholar 

  16. Wolf, S.F., Jolly, D.J., Lunnen, K.D., Friedmann, T., and Migeon, B.R. (1984).Proc. Natl. Acad. Sci. U.S.A. 81:2806–2810.

    PubMed  Google Scholar 

  17. Yen, P.H., Patel, P.I., Chinault, A.C., Mohandas, T., and Shapiro, L.J. (1984).Proc. Natl. Acad. Sci. U.S.A. 81:1759–1763.

    PubMed  Google Scholar 

  18. Dynan, W.S., and Tjian, R., (1985).Nature 316:774–778.

    PubMed  Google Scholar 

  19. Maniatis, T., Goodbourn, S., and Fischer, J.A. (1987).Science 236:1237–1245.

    PubMed  Google Scholar 

  20. Riggs, A.D., Singer-Sam, J., and Keith, D.H. (1985). InBiochemistry and Biology of DNA Methylation, (eds.) Cantoni, G.L., Razin, A. (Alan R. Liss, New York), pp. 211–222.

    Google Scholar 

  21. Dignam, J.D., Lebovitz, R.M., and Roeder, R.G. (1983).Nucleic Acids Res. 11:1475–1489.

    PubMed  Google Scholar 

  22. Chamberlin, M., Kinston, R., Gilman, M., Wiggs, J., and deVera, A. (1983). InMethods in Enzymology—Recombinant DNA, (eds.) Wu, R., Grossman, L., and Moldave, K. (Academic Press, New York), pp. 540–582.

    Google Scholar 

  23. Carthew, R.W., Chodosh, L.A., and Sharp, P.A. (1985).Cell 43:439–448.

    PubMed  Google Scholar 

  24. Singh, H., Sen, R., Baltimore, D., and Sharp, P.A. (1986).Nature 319:154–158.

    PubMed  Google Scholar 

  25. Yang, T.P., Patel, P.I., Chinault, A.C., Stout, J.T., Jackson, L.G., Hildebrand, B.M., and Caskey, C.T. (1984).Nature 310:412–414.

    PubMed  Google Scholar 

  26. Maniatis, T., Fritsch, E.F., and Sambrook, J. (1982).Molecular Cloning: A Laboratory Manual, (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York).

    Google Scholar 

  27. Jones, K.A., Yamamoto, K.R., and Tjian, R. (1985).Cell 42:559–572.

    PubMed  Google Scholar 

  28. Melton, D.W., Konecki, D.S., Brennand, J., and Caskey, C.T. (1984).Proc. Natl. Acad. Sci. U.S.A. 81:2147–2151.

    PubMed  Google Scholar 

  29. Dush, M.D., Sikela, J.M., Khan, S.A., Tischfield, J.A., and Stambrook, P.J. (1985).Proc. Natl. Acad. Sci. U.S.A. 82:2731–2735.

    PubMed  Google Scholar 

  30. Farnham, P.J., and Schimke, R.T. (1985).J. Biol. Chem. 260:7675–7680.

    PubMed  Google Scholar 

  31. Gitschier, J., Wood, W.I., Goralka, T.M., Wion, K.L., Chen, E.Y., Eaton, D.H., Vehar, G.A., Capon, D.J., and Lawn, R.M. (1984).Nature 312:326–330.

    PubMed  Google Scholar 

  32. Minghetti, P.P., Ruffner, D.E., Kuange, W.-J., Dennison, O.E., Hawkins, J.W., Beattie, W.G., and Dugaiczyk, A. (1986).J. Biol. Chem. 261:6747–6757.

    PubMed  Google Scholar 

  33. Weil, P.A., Luse, D.S., Segall, J., and Roeder, R.G. (1979).Cell 18:469–484.

    PubMed  Google Scholar 

  34. Maxam, A.M., and Gilbert, W. (1977).Proc. Natl. Acad. Sci. U.S.A. 74:560–564.

    PubMed  Google Scholar 

  35. Briggs, M.R., Kadonaga, J.T., Bell, S.P., and Tijan, R. (1986).Science 234:47–52.

    PubMed  Google Scholar 

  36. Staudt, L.M., Singh, H., Sen, R., Wirth, T., Sharp, P.A., and Baltimore, D. (1986).Nature 323:640–643.

    PubMed  Google Scholar 

  37. Piette, J., and Yaniv, M. (1986).Nucleic Acids Res. 14:9595–9611.

    PubMed  Google Scholar 

  38. Jones, K.A., Kadonaga, J.T., Rosenfeld, P.J., Kelly, T.J., and Tjian, R. (1987).Cell 48:79–89.

    PubMed  Google Scholar 

  39. Dorn, A., Bollekens, J., Staub, A., Benoist, C., and Mathis, D. (1987).Cell 50:863–872.

    PubMed  Google Scholar 

  40. Buschhausen, G., Wittig, B., Graessmann, M., and Graessmann, A. (1987).Proc. Natl. Acad. Sci. U.S.A. 84:1177–1181.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Biology, Beckman Research Institute of the City of Hope, 91010, Duarte, California

    Thomas P. Yang, Judith Singer-Sam, Josephine C. Flores & Arthur D. Riggs

Authors
  1. Thomas P. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Judith Singer-Sam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Josephine C. Flores
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arthur D. Riggs
    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

Yang, T.P., Singer-Sam, J., Flores, J.C. et al. DNA binding factors for the CpG-rich island containing the promoter of the human X-linkedPGK gene. Somat Cell Mol Genet 14, 461–472 (1988). https://doi.org/10.1007/BF01534712

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01534712

Keywords

Search

Navigation