Imprinted MousE X-Inactivation

All cells of the early female mouse embryo undergo inactivation of the paternal X-chromosome. Imprinted X-inactivation is a paradigm of transgenerational epigenetic inheritance, since the transcriptional fates of the two X-chromosomes is determined by their parent-of-origin. A hallmark of both imprinted and random X-inactivation is the expression of the Xist non-coding RNA from the prospective inactive-X. In the early mouse embryo, Xist RNA is only expressed from the paternal-X due to imprinted X-inactivation.

Soon after Xist RNA is transcribed from the paternal-X, Xist RNA physically coats the paternal X-chromosome, followed closely by accumulation of proteins such as the Polycomb group along with the histone modifications they enact on the paternal-X. These proteins, recruited by Xist RNA, are in turn posited to bring about silencing of paternal X-linked genes.

While Xist RNA stabilizes the inactive state of the paternal-X (Kalantry et al., 2009), the Tsix non-coding RNA is expressed solely from the active, maternal X-chromosome. Tsix expression maintains silencing of Xist on the active X-chromosome and thus prevents its ectopic inactivation once X-inactivation has occurred during both imprinted and random X-inactivation (see Maclary et al., 2014; Gayen et al., 2015).

An active area of research in the lab is to understand when and how Xist RNA, Tsix RNA, and novel inactive X-linked lncRNAs that we have discovered contribute to both imprinted and random X-inactivation.