In mice, X inactivation is preceded by in cis Xist expression. Initial
ly, normal female embryos express the paternal Xist allele exclusively
, preceding imprinted X inactivation in the trophectoderm Later expres
sion of Xist alleles is random, preceding random X inactivation in the
epiblast lineage. In this study using uniparental embryos, we demonst
rate that Xist expression is initially dictated solely by parental imp
rinting, causing expression of all paternal alleles. Maternal alleles
remain repressed, irrespective of X chromosome number. At the compacti
ng morula stage, this parental imprint is erased, and the mechanism co
unting the X chromosomes imposes appropriate Xist expression with resp
ect to chromosome number. Our results also suggest that Xist expressio
n may itself be regulated by a novel imprinted maternally expressed ge
ne.