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Silent sifter demo
Silent sifter demo




The expression and DNA methylation profiles of the Moloney murine leukemia virus (MMLV) have been investigated in embryonic carcinoma cells (ECs) and embryonic stem cells (ESCs) ( Niwa et al., 1983). 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.

silent sifter demo

Embryonic stem cells (ESCs) repress the expression of exogenous proviruses and endogenous retroviruses (ERVs).






Silent sifter demo