Methylation patterns in the gene for the alpha subunit of chorionic gonadotropin are inherited with variable fidelity in clonal lineages of human fibroblasts.

Cytosine methylation in DNA of an endogenous single-copy gene locus, the alpha-subunit of human chorionic gonadotropin (alpha-hCG), was assessed in a mass culture and individual clonal lineages of human diploid fibroblasts. Progressive hypomethylation at -CCGG- sites in this gene occurred during the replicative lifespan of the mass culture and was shown to arise randomly during clonal expansion. Thus, some clones and subclones lost -CCGG- methylation in the alpha-hCG gene region while others maintained essentially complete methylation. These data indicate significant interclonal variability in the fidelity with which DNA methylation is transmitted in an endogenous gene.