This silencing has likely evolved for the protection of germline cells from insertional mutagenesis ( Gaudet et al., 2004 Walsh et al., 1998). The expression of proviruses and endogenous retroviruses (ERVs) is restricted in pluripotent stem cells ( Feuer et al., 1989 Niwa et al., 1983 Teich et al., 1977). Our study reports a genome-wide atlas of functional nodes that mediate proviral silencing in ESCs and illuminates the comprehensive, interconnected, and multi-layered genetic and epigenetic mechanisms by which ESCs repress retroviruses within the genome. Chaf1a reinforces transcriptional repression via its interaction with members of the NuRD complex (Kdm1a, Hdac1/2) and Eset, while Sumo2 orchestrates the provirus repressive function of the canonical Zfp809/Trim28/Eset machinery by sumoylation of Trim28. ChIP-seq analysis demonstrates direct recruitment of Chaf1a and Sumo2 to ERVs. RNA-seq analysis uncovered the roles of Chaf1a/b and sumoylation modifiers in the repression of ERVs. Histone chaperones (Chaf1a/b), sumoylation factors (Sumo2/Ube2i/Sae1/Uba2/Senp6), and chromatin modifiers (Trim28/Eset/At-f7ip) are key determinants that establish provirus silencing. Here, we systematically dissected the cellular factors involved in provirus repression in embryonic carcinomas (ECs) and ESCs by a genome-wide siRNA screen. Embryonic stem cells (ESCs) repress the expression of exogenous proviruses and endogenous retroviruses (ERVs).

Silent sifter demo