Unraveling the role of Xist in X chromosome inactivation: insights from rabbit model and deletion analysis of exons and repeat A

Abstract

X chromosome inactivation (XCI) is a dosage compensation process that aims to equalize the expression of X-linked genes between males and females. Initiation of XCI relies on Xist, which is continuously expressed in somatic cells during XCI maintenance. How Xist impacts XCI maintenance remains unclear, and its functional motifs remain unclear. In this study, we conducted a comprehensive analysis of the Xist. The results demonstrate that rabbits serve as an ideal non-primate animal model for investigating the functions of Xist in vivo. And homozygous knockout of exon 1, exon 6 and repeat A in females resulted in embryonic lethality. However, X{Delta}ReAX females with Xist expression from the intact X chromosome, did not display any abnormalities. Interestingly, there were no significant differences between females with homozygous knockout of exons 2-5 and wild-type rabbits. This suggests that exons 2, 3, 4, and 5 of Xist are less important for XCI. These insights provide valuable knowledge about the functional mechanism of Xist.