Abstract
To determine if expression of genes on the inactive X is inducible in human cells, we looked for reactivation events in a clone of fibroblasts transformed with origin-defective SV40. The karyotype of these cells was grossly heteroploid so that the aneuploidy associated with SV40 transformation occurs even in the absence of viral replication. This transformed clone, heterozygous for hypoxanthine phosphoribosyltransferase (HPRT), lacks HPRT activity, as the mutant allele is on the active X and the normal allele on the inactive X. Reactivation of the HPRT + allele on the inactive X was observed at a frequency of 6 x 10 −5 per cell and increased approximately eightfold following treatment with the cytidine analogs 5-azacytidine (5azaC) and 5-azadeoxycytidine. The fact that spontaneous reactivation is detectable in some clones, but not all, suggests that the environment of the SV40-transformed cell, although not sufficient to induce generalized derepression, increases the frequency of rare reactivation events. The methylation pattern at the HPRTlocus revealed transformation-associated alterations that may have predisposed these cells to reactivation events, spontaneous as well as 5azaC-induced.
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Literature cited
Lyon, M.F. (1973).Biol. Rev. 47:1–35.
Gartler, S.M., Liskay, R.M., Campbell, B.K., Sparks, R., and Grant, N. (1972).Cell Differ. 1:215–218.
Migeon, B.R., Wolf, S.F., Axelman, J., Kaslow, D.C., and Schmidt, M. (1985).Proc. Natl. Acad. Sci. U.S.A. 82:3390–3394.
Migeon, B.R., Wolf, S.F., Mareni, C., and Axelman, J. (1982).Cell 29:595–600.
Mohandas, T., Sparks, R.S., and Shapiro, L.J. (1981).Science 211:393–396.
Graves, J.A.M. (1982).Exp. Cell Res. 141:99–105.
Jones, P.A., Taylor, S.M., Mohandas, T., and Shapiro, L.J. (1982).Proc. Natl. Acad. Sci. U.S.A. 79:1215–1219.
Lester, S.C., Korn, N.J., and DeMars, R. (1982).Somat. Cell Genet. 8:265–284.
Hors-Cayla, M.C., Heuertz, S., and Frezal, J. (1983).Somat. Cell Genet. 9:645–657.
Kahan, B., and DeMars, R. (1975).Proc. Natl. Acad. Sci. U.S.A. 72:1510–1514.
Hellkuhl, B., and Grzeschik, K.H. (1978).Cytogenet. Cell Genet. 22:527–530.
Jones, P.A., and Taylor, S.M. (1980).Cell 20:85–93.
Graves, J.A.M., and Young, G.J. (1982).Exp. Cell Res. 141:87–97.
Comings, D.E. (1966).Lancet 2:1137–1138.
Migeon, B.R. (1972).Nature 239:87–89.
Wolf, S.F., and Migeon, B.R. (1982).Nature 295:667–671.
Romeo, G., and Migeon, B.R. (1975).Humangenetik 29:165–170.
Raskind, W.H., and Gartler, S.M. (1979).Somat. Cell Genet. 5:945–955.
Sack, G.H. (1981).In Vitro 17:1–19.
Gluzman, Y., Frisque, R.J., and Sambrook, J. (1980).Cold Spring Harbor Symp. Quant. Biol. 44:293–299.
Wolf, S.F., Jolly, D.J., Lunnen, K.D., Friedman, T., and Migeon, B.R. (1984).Proc. Natl. Acad. Sci. U.S.A. 81:2806–2810.
Migeon, B.R., Sprenkle, J.A., and Do, T.T. (1978). InGenetic Mosaics and Chimeras in Mammals, (ed.) Russell, L.B. (Plenum Press, New York), pp. 329–337.
Gluzman, Y., Sambrook, J.F., and Frisque, R.J. (1980).Proc. Natl. Acad. Sci. U.S.A. 77:3898–3902.
Corsaro, C.M., and Pearson, M.L. (1981).Somat. Cell Genet. 7:603–616.
Small, J.A., Blair, D.G., Showalter, S.D., and Scangos, G.A. (1985).Mol. Cell. Biol. 5:642–648.
Yunis, J., and Chandler, M.E. (1977). InProgress in Clinical Pathology, (eds.) Stefanini, M., and Hossaini, A.A. (Grune & Stratton, New York), pp. 267–288.
Casperson, T., Lomakaa, G., and Zech, L. (1971).Hereditas 67:89–102.
Schmidt, M., Wolf, S.F., and Migeon, B.R. (1985).Exp. Cell Res. 158:301–310.
Christy, B., and Scangos, G. (1982).Proc. Natl. Acad. Sci. U.S.A. 79:6299–6303.
Koprowski, H., Ponten, J.A., Jensen, F., Ravdin, R.G., Moorhead, P., and Saksela, E. (1962).J. Cell. Comp. Physiol. 59:281–292.
Moorhead, P.S., and Saksela, E. (1963).J. Cell. Comp. Physiol. 62:57–83.
Wolman, S.R., Hirschhorn, K., and Todaro, G.J. (1964).Cytogenetics 3:45–61.
Zuna, R.G., and Lehman, J.M. (1977).J. Natl. Cancer Inst. 58:1463–1472.
Mohandas, T., Sparkes, R.S., Bishop, D.F., Desnick, R.J., and Shapiro, L.J. (1984).Am. J. Hum. Genet. 36:916–925.
Yen, P.H., Patel, P., Chinault, A.C., Mohandas, T., and Shapiro, L.J. (1984).Proc. Natl. Acad. Sci. U.S.A. 81:1759–1763.
Cooper, D.N., Taggart, M.H., and Bird, A.P. (1985).Nucleic Acids Res. 11:647–658.
Wolf, S.F., and Migeon, B.R. (1985).Nature 314:467–469.
Kingston, R.E., Baldwin, A.S., and Sharp, A. (1985).Cell 41:3–5.
Nadon, N., Sekhon, G., Chang, C., Peterson, J., Strandtmann, J., Brown, L., and DeMars, R. (1985).Am. J. Hum. Genet. 37:A234.
Paterno, G.D., Adra, C.N., and McBurney, M.W. (1985).Mol Cell. Biol. 5:2705–2712.
Gama-Sosa, M.A., Slagel, V.A., Trewyn, R.W., Oxenhandler, R., Kuo, K.C., Gehrke, C.W., and Ehrlich M. (1983).Nucleic Acids Res. 11:6883–6894.
Kautiainen, T.L., and Jones, P.A. (1986).J. Biol. Genet. 4:1594–1598.
Levitt, L.J., Boss, G.R., and Erbe, R.W. (1986).Cancer 57:764–768.
Small, M.B., Gluzman, Y., and Ozer, H.L. (1982).Nature 296:671–672.
Schwartzbaum, S., Halpern, R., and Diamond, B. (1984).J. Immunol. 132:1158–1162.
Littlefield, J.W. (1976).Variation, Senescence, and Neoplasia, (Harvard University Press, Cambridge).
Nagata, Y., Diamond, B., and Bloom, B.R. (1983).Nature 306:597–599.
Canaani, D., Naiman, T., Teitz, T., and Berg, P. (1986).Somat. Cell Mol. Genet. 12:13–20.
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Beggs, A.H., Axelman, J. & Migeon, B.R. Reactivation of X-linked genes in human fibroblasts transformed by origin-defective SV40. Somat Cell Mol Genet 12, 585–594 (1986). https://doi.org/10.1007/BF01671944
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DOI: https://doi.org/10.1007/BF01671944