Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation [irCLIP-seq]

We show that Spen, an Xist binding repressor protein essential for XCI, binds to ancient retroviral RNA transcribed genome-wide, performing a surveillance role to recruit chromatin silencing machinery to these parasitic loci. Spen inactivation leads to de-repression of endogenous retroviral (ERV) elements in embryonic stem cells, with gain of chromatin accessibility, active histone modifications, and ERV RNA transcription. Spen binds directly to ERV RNAs that are highly similar to the A-repeat of Xist, a region critical for Xist-mediated gene silencing. ERV RNA and Xist A-repeat bind the RRM3 domain of Spen in a competitive manner and insertion of an ERV into an A-repeat deficient Xist rescues binding of Xist RNA to Spen. Overall design: irCLIP-seq was performed in WT and SpenKO mESCs in vivo and vitro conditions . At least two Libraries(2 replicates per line) were sequenced on an Illumina Illumina Nextseq