Evidence for DNA modification in the maintenance of X-chromosome inactivation of adult mouse tissues.

The role of DNA modification in the maintenance of mammalian X-chromosome inactivation was investigated by using the technique of DNA transformation in mammalian cells. The ability of inactive X-chromosome DNA from adult mouse tissues to act in transformation for the X-linked hypoxanthine phosphoribosyltransferase gene (Hprt) could be ascertained by utilizing a recently discovered electrophoretic variant form of the hypoxanthine phosphoribosyltransferase enzyme and a previously available X:autosome translocation. Our findings indicate that inactive X-chromosome DNA from several tissues of adult female mice is strikingly inefficient, in comparison to active X-chromosome DNA, in eliciting genetic transformation for hypoxanthine phosphoribosyltransferase. These results provide in vivo evidence that is consistent with DNA modification playing an important role in the maintenance of X-chromosome inactivation.