Differences in the DNA of the inactive X chromosomes of fetal and extraembryonic tissues of mice.

We have examined the role of DNA modification in X chromosome inactivation of fetal tissues of the mouse using DNA-mediated gene transfer for the gene hypoxanthine phosphoribosyltransferase (HPRT). Two types of tissues have been examined with respect to randomness of inactivation in 14-day mouse conceptuses: 1) fetal tissue, which undergoes random inactivation of either the maternal or paternal X; and 2) yolk sac endoderm tissue, an extraembryonic membrane, which normally undergoes nonrandom inactivation of the paternal X. Exploiting an electrophoretic variant of HPRT as a means to mark the active and inactive HPRT alleles we provide evidence that: 1) inactive X DNA of the fetus at 14 days behaves like that of both adult tissue and cell lines in that the inactive X DNA is not efficient in gene transfer; and 2) in contrast, inactive X DNA from yolk sac endoderm is functional in gene transfer. Thus, despite the similarity in single active X chromosome expression in yolk sac endoderm and somatic tissues, there appears to be a difference at the level of DNA modification between these two tissues.