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Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells
Author(s) -
Bin Yang,
Chadi El Farran,
Hongchao Guo,
Tao Yu,
Haitong Fang,
Haofei Wang,
S. P. Schlesinger,
Samantha Seah,
Germaine Goh,
Suat Peng Neo,
Yinghui Li,
Matthew C. Lorincz,
Vinay Tergaonkar,
T. M. Lim,
Lingyi Chen,
Jayantha Gunaratne,
James J. Collins,
Stephen P. Goff,
George Q. Daley,
Hu Li,
Frédéric Bard,
YuinHan Loh
Publication year - 2015
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2015.08.037
Subject(s) - biology , provirus , sumo protein , chromatin , gene silencing , embryonic stem cell , genetics , psychological repression , histone , endogenous retrovirus , retrotransposon , epigenetics , polycomb group proteins , microbiology and biotechnology , genome , transcription factor , repressor , gene , gene expression , transposable element , ubiquitin
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.

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