![]() ![]() ![]() Insertion of an ERV into an A-repeat deficient Xist rescues binding of Xist RNA to Spen and results in strictly local gene silencing in cis. ERV RNA and Xist A-repeat bind the RRM domains of Spen in a competitive manner. Spen binds directly to ERV RNAs that show structural similarity to the A-repeat of Xist, a region critical for Xist-mediated gene silencing. ![]() Spen loss activates a subset of endogenous retroviral (ERV) elements in mouse embryonic stem cells, with gain of chromatin accessibility, active histone modifications, and ERV RNA transcription. Here we show that Spen, an Xist-binding repressor protein essential for XCI, binds to ancient retroviral RNA, performing a surveillance role to recruit chromatin silencing machinery to these parasitic loci. The Xist lncRNA mediates X chromosome inactivation (XCI). ![]()
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