Stability of DNA methylation of the human hypoxanthine phosphoribosyltransferase gene.

Methylation sensitive restriction enzymes were used to evaluate the methylation level of several restriction sites near human hypoxanthine phosphoribosyltransferase (HPRT) genes on active and inactive X chromosomes. DNA samples from leukocytes, from clonally derived fibroblasts, and from independent mouse-human hybrid lines isolated from the fusion of A-9 cells and these clonally derived human cells were studied. Comparison of the methylation patterns shows that restriction sites may show variable or constant methylation among tissues and clones, and heritability of methylation is also different among restriction sites. Methylation is more stable at sites whose methylation status correlate well with HPRT activity. Our results suggest that the methylation of certain cytosine residues may critically affect gene activity and that the methylation pattern of these sites is stably inherited.