Regulation of X-linked gene expression during early mouse development by <i>Rlim</i>.

Abstract

Mammalian X-linked gene expression is highly regulated as female cells contain two and male one X chromosome (X). To adjust the X gene dosage between genders, female mouse preimplantation embryos undergo an imprinted form of X chromosome inactivation (iXCI) that requires both <i>Rlim</i> (also known as Rnf12) and the long non-coding RNA <i>Xist</i>. Moreover, it is thought that gene expression from the single active X is upregulated to correct for bi-allelic autosomal (A) gene expression. We have combined mouse genetics with RNA-seq on single mouse embryos to investigate functions of <i>Rlim</i> on the temporal regulation of iXCI and <i>Xist</i>. Our results reveal crucial roles of <i>Rlim</i> for the maintenance of high <i>Xist</i> RNA levels, <i>Xist</i> clouds and X-silencing in female embryos at blastocyst stages, while initial <i>Xist</i> expression appears <i>Rlim</i>-independent. We find further that X/A upregulation is initiated in early male and female preimplantation embryos.