X Chromosome inactivation (XCI) silences one copy of most X-linked genes in female mammals. Notably, human and mouse differ strikingly in the number and organization of the genes that escape XCI. While on the human X Chromosome (Chr) escape genes are organized in domains, the few known genes that escape inactivation in the mouse appear to be isolated. Here we characterize the gene Cxorf26 and adjacent noncoding transcripts that map to XqD. We assess allelic expression in a nonrandomly X-inactivated cell line and directly demonstrate that 2610029G23Rik (Cxorf26) and its head-to-head neighbor (5530601H04Rik) escape X inactivation, creating a small escape domain. Both genes are robustly expressed from the inactive X Chr at approximately 50 and 30% of the expression levels of the active X, respectively. Additionally, consistent with XCI escape, the first exon of Cxorf26 is embedded within an unmethylated CpG island. To extend these results, we assayed ncRNAs adjacent to three other escape genes, Eif2s3x, Kdm5c, and Ddx3x. By allelic expression, three ncRNAs (D330035k16Rik, D930009k15Rik, and Gm16481) also escape X inactivation in the mouse, consistent with previous studies that reported female-biased expression. Altogether, these results establish that mouse escapees, like their human counterparts, can be clustered. Moreover, the fact that these ncRNAs are not found on the human X raises intriguing questions about potential regulatory roles of rapidly evolving ncRNAs in controlling escape gene expression.
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