Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells
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), s...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/108347 https://orcid.org/0000-0002-5560-8246 |
| _version_ | 1811096321358036992 |
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| author | 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 Li, Yinghui Lorincz, Matthew C. Tergaonkar, Vinay Lim, Tit-Meng Chen, Lingyi Gunaratne, Jayantha Goff, Stephen P. Daley, George Q. Li, Hu Bard, Frederic A. Loh, Yuin-Han Collins, James J. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering 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 Li, Yinghui Lorincz, Matthew C. Tergaonkar, Vinay Lim, Tit-Meng Chen, Lingyi Gunaratne, Jayantha Goff, Stephen P. Daley, George Q. Li, Hu Bard, Frederic A. Loh, Yuin-Han Collins, James J. |
| author_sort | Yang, Bin Xia |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:41:58Z |
| format | Article |
| id | mit-1721.1/108347 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:41:58Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1083472022-10-03T07:42:08Z Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells 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 Li, Yinghui Lorincz, Matthew C. Tergaonkar, Vinay Lim, Tit-Meng Chen, Lingyi Gunaratne, Jayantha Goff, Stephen P. Daley, George Q. Li, Hu Bard, Frederic A. Loh, Yuin-Han Collins, James J. Massachusetts Institute of Technology. Department of Biological Engineering Collins, James J. 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. 2017-04-21T17:23:53Z 2017-04-21T17:23:53Z 2015-09 2015-07 Article http://purl.org/eprint/type/JournalArticle 0092-8674 1097-4172 http://hdl.handle.net/1721.1/108347 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 https://orcid.org/0000-0002-5560-8246 en_US http://dx.doi.org/10.1016/j.cell.2015.08.037 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | 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 Li, Yinghui Lorincz, Matthew C. Tergaonkar, Vinay Lim, Tit-Meng Chen, Lingyi Gunaratne, Jayantha Goff, Stephen P. Daley, George Q. Li, Hu Bard, Frederic A. Loh, Yuin-Han Collins, James J. Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells |
| title | Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells |
| title_full | Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells |
| title_fullStr | Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells |
| title_full_unstemmed | Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells |
| title_short | Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells |
| title_sort | systematic identification of factors for provirus silencing in embryonic stem cells |
| url | http://hdl.handle.net/1721.1/108347 https://orcid.org/0000-0002-5560-8246 |
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