Derepression of genes on the human inactive X chromosome: evidence for differences in locus-specific rates of derepression and rates of transfer of active and inactive genes after DNA-mediated transformation.

Abstract

Mouse-human hybrid cells that contained an inactive human X chromosome were treated with agents known to alter gene expression and to perturb DNA methylation. 5-Azacytidine greatly increased the rate of derepression of HPRT on the inactive X, while butyrate and dimethyl sulfoxide had smaller effects. Ethionine did not change the rate of derepression. Derepression of two other X-chromosomal loci, PGK and GPD, was also detected. The rate of derepression of PGK was 20-fold higher than the rate for HPRT. Derepression events at the two loci appeared to be independent. Hybrids expressing derepressed X-chromosomal genes had more variable levels of human enzyme activities when compared to control hybrids. HPRT+ clones did not appear after transfer of purified DNA from a cell hybrid containing an inactive human X into HPRT- recipients, but such clones did appear after transfer of DNA from derivative cells in which HPRT had been derepressed.