Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells
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Collins_Systematic identification.pdf
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Author(s)
Yang, Bin Xia
EL Farran, Chadi A.
Guo, Hong Chao
Yu, Tao
Fang, Hai Tong
Wang, Hao Fei
Schlesinger, Sharon
Seah, Yu Fen Samantha
Goh, Germaine Yen Lin
Neo, Suat Peng
Date Issued
September 2015
Journal
Cell
Publisher
Elsevier
Citation
Yang, Bin Xia; EL Farran, Chadi A.; Guo, Hong Chao; Yu, Tao; Fang, Hai Tong; Wang, Hao Fei; Schlesinger, Sharon et al. “Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells.” Cell 163, no. 1 (September 2015): 230–245. © 2015 Elsevier Inc
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1016/j.cell.2015.08.037
