To study whether cloning resets the epigenetic differences between the two
X chromosomes of a somatic female nucleus, we monitored X inactivation in c
loned mouse embryos. Both X chromosomes were active during cleavage of clon
ed embryos, followed by random X inactivation in the embryo proper. In the
trophectoderm (TE), X inactivation was nonrandom with the inactivated X of
the somatic donor being chosen for inactivation. When female embryonic stem
cells with two active X chromosomes were used as donors, random X inactiva
tion was seen in the TE and embryo. These results demonstrate that epigenet
ic marks can be removed and reestablished on either X chromosome during clo
ning. Our results also suggest that the epigenetic marks imposed on the X c
hromosomes during gametogenesis, responsible for normal imprinted X inactiv
ation in the TE, are functionally equivalent to the marks imposed on the ch
romosomes during somatic X inactivation.