Imprinting and X chromosome counting mechanisms determine Xist expression in early mouse development

Abstract

In mice, X inactivation is preceded by in cis Xist expression. Initially, normal female embryos express the paternal Xist allele exclusively, preceding imprinted X inactivation in the trophectoderm. Later expression of Xist alleles is random, preceding random X inactivation in the epiblast lineage. In this study using uniparental embryos, we demonstrate that Xist expression is initially dictated solely by parental imprinting, causing expression of all paternal alleles. Maternal alleles remain repressed, irrespective of X chromosome number. At the compacting morula stage, this parental imprint is erased, and the mechanism counting the X chromosomes imposes appropriate Xist expression with respect to chromosome number. Our results also suggest that Xist expression may itself be regulated by a novel imprinted maternally expressed gene.