Abstract
Epigenetic changes at one, two, or three loci were induced with 5-azacytidine in CHO-K1 cells, using markers (proline dependence, asparagine dependence, and thymidine kinase deficiency) which respond by high-frequency reversion to wild-type states. The observed incidence of dual or triple revertants was compared with the frequency expected by chance as the product of single frequencies measured separately for the markers involved. Values observed for dual reversions consistently exceeded levels predicted by this purely stochastic model, and for triple reversion the divergence was 1000-fold. Coordinate responses could account for this disparity, if minority cell types with higher reactivity to 5-azacytidine exist in target cell populations. To test this hypothesis, single colonies were isolated under nonselective conditions from a mass culture of CHO-K1 cells that had been treated with 5-azacytidine. These clones showed wide and reproducible differences in competence for reversion from proline dependence to independence. Our data thus suggest that simultaneity of epigenetic changes depends on random events which are modulated by a mosaic of inductive potentials within individual cells of the reacting system.
Similar content being viewed by others
Literature cited
Harris, M. (1984).Somat. Cell Mol. Genet. 10:615–624.
Harris, M. (1986).Somat. Cell Mol. Genet. 12:459–466.
Harris, M. (1982).Cell 29:483–492.
Bradley, W.E.C. (1984).Mol. Cell Biol. 3:1172–1181.
Harris, M. (1984).Somat. Cell Mol. Genet. 10:275–281.
Taylor, S.M., and Jones, P.A. (1979).Cell 17:771–779.
Jones, P.A., and Taylor S.M. (1980).Cell 20:85–93.
Mohandas, T., Sparkes, R.S., and Shapiro, L.J. (1981).Science 211:393–396.
Harris, M. (1975).J. Cell Physiol. 86:413–430.
Lowry, O.H., Rosebrough, J.A., Farr, A.L., and Randall, R.J. (1951).J. Biol. Chem. 193:265–275.
Wise, T. (1985). PhD thesis (Zoology), University of California. 114 pp.
Wise, T., and Harris, M. (1986). (submitted for publication).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Harris, M. Simultaneous induction of epigenetic variants. Somat Cell Mol Genet 12, 567–573 (1986). https://doi.org/10.1007/BF01671942
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01671942