Pluto Bioinformatics

GSE36463: Profiling of differential allelic expression in mouse placental tissues from two reciprocal crosses at embryonic day 13.5 and 17.5.

Bulk RNA sequencing

Mammals achieve parity in expression of X linked genes in somatic tissue of males and females through the mechanism of X inactivation. Not all X-linked genes are silenced on the inactivated X, and genes that escape X-inactivation provide key insights about the mechanism of X inactivation. In humans, 15% of X-linked genes escape random X inactivation whereas in mouse 3% of X-linked genes escape inactivation. In marsupials and mouse, extraembryonic tissues (which give rise to the placenta) display another form of dosage compensation called imprinted X inactivation. Imprinted X inactivation is not random, as it is always the paternal X that is inactivated. There are as yet no reports in the literature of genes that might escape imprinted X inactivation. Here, we performed a deep RNA-seq study in mouse placenta samples from reciprocal crosses and discovered that 7.4% (21/282) of X-linked genes escape imprinted X inactivation. Strikingly, there is zero overlap between the set of imprinted X inactivation escapers and random X inactivation escapers. Imprinted X inactivation escapers are stable and show >35% paternal expression compared to >10% expression from the inactive X for random X inactivation escapers. Imprinted X inactivation escapers are all of clear functional importance to the placenta, and they are strongly clustered on the X. GO analysis reveals that glycoproteins and transmembrane proteins are significantly enriched among imprinted X inactivation escapers. The X-added region (XAR) of the eutherian mammal X is autosomal in marsupials and these genes were added to the X in eutherian mammals since the time of common ancestry. Fully 70% of the genes in the XAR escape random X inactivation, as though they have yet to acquire normal dosage compensation. But fewer than 10% of the genes in the X-added region (XAR) escape imprinted X inactivation, consistent with a imprinted X inactivation being a default state, and escape occurs only for genes requiring biallelic expression. The deep interspecific conservation of X inactivation escaper status that we find across mammals (including marsupials) despite the radical variation in mechanism provides strong evidence that there is a functional basis for escaper genes to retain their biallelic expression. Discussion of the specific genes that are escapers of imprinted X inactivation will suggest reasons for this functional conservation. SOURCE: Andrew Clark (ac347@cornell.edu) - Cornell University