| Literature DB >> 26365490 |
Bin Xia Yang1, Chadi A El Farran2, Hong Chao Guo3, Tao Yu2, Hai Tong Fang1, Hao Fei Wang2, Sharon Schlesinger4, Yu Fen Samantha Seah1, Germaine Yen Lin Goh5, Suat Peng Neo6, Yinghui Li7, Matthew C Lorincz8, Vinay Tergaonkar9, Tit-Meng Lim10, Lingyi Chen3, Jayantha Gunaratne11, James J Collins12, Stephen P Goff13, George Q Daley14, Hu Li15, Frederic A Bard16, Yuin-Han Loh17.
Abstract
Embryonic stem cells (ESCs) repress the expression of exogenous proviruses and endogenous retroviruses (ERVs). Here, we systematically dissected the cellular factors involved in provirus repression in embryonic carcinomas (ECs) and ESCs by a genome-wide siRNA screen. Histone chaperones (Chaf1a/b), sumoylation factors (Sumo2/Ube2i/Sae1/Uba2/Senp6), and chromatin modifiers (Trim28/Eset/Atf7ip) are key determinants that establish provirus silencing. RNA-seq analysis uncovered the roles of Chaf1a/b and sumoylation modifiers in the repression of ERVs. ChIP-seq analysis demonstrates direct recruitment of Chaf1a and Sumo2 to ERVs. 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. 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.Entities:
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Year: 2015 PMID： 26365490 PMCID： PMC4686136 DOI： 10.1016/j.cell.2015.08.037
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582