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Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs
TLR7/9 signals are capable of mounting massive interferon (IFN) response in plasmacytoid dendritic cells (pDCs) immediately after viral infection, yet the involvement of epigenetic regulation in this process has not been documented. Here, we report that zinc finger CXXC family epigenetic regulator C...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413332/ https://www.ncbi.nlm.nih.gov/pubmed/28416650 http://dx.doi.org/10.1084/jem.20161149 |
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author | Ma, Shixin Wan, Xiaoling Deng, Zihou Shi, Lei Hao, Congfang Zhou, Zhenyuan Zhou, Chun Fang, Yiyuan Liu, Jinghua Yang, Jing Chen, Xia Li, Tiantian Zang, Aiping Yin, Shigang Li, Bin Plumas, Joel Chaperot, Laurence Zhang, Xiaoming Xu, Guoliang Jiang, Lubin Shen, Nan Xiong, Sidong Gao, Xiaoming Zhang, Yan Xiao, Hui |
author_facet | Ma, Shixin Wan, Xiaoling Deng, Zihou Shi, Lei Hao, Congfang Zhou, Zhenyuan Zhou, Chun Fang, Yiyuan Liu, Jinghua Yang, Jing Chen, Xia Li, Tiantian Zang, Aiping Yin, Shigang Li, Bin Plumas, Joel Chaperot, Laurence Zhang, Xiaoming Xu, Guoliang Jiang, Lubin Shen, Nan Xiong, Sidong Gao, Xiaoming Zhang, Yan Xiao, Hui |
author_sort | Ma, Shixin |
collection | PubMed |
description | TLR7/9 signals are capable of mounting massive interferon (IFN) response in plasmacytoid dendritic cells (pDCs) immediately after viral infection, yet the involvement of epigenetic regulation in this process has not been documented. Here, we report that zinc finger CXXC family epigenetic regulator CXXC5 is highly expressed in pDCs, where it plays a crucial role in TLR7/9- and virus-induced IFN response. Notably, genetic ablation of CXXC5 resulted in aberrant methylation of the CpG-containing island (CGI) within the Irf7 gene and impaired IRF7 expression in steady-state pDCs. Mechanistically, CXXC5 is responsible for the recruitment of DNA demethylase Tet2 to maintain the hypomethylation of a subset of CGIs, a process coincident with active histone modifications and constitutive transcription of these CGI-containing genes. Consequently, CXXC5-deficient mice had compromised early IFN response and became highly vulnerable to infection by herpes simplex virus and vesicular stomatitis virus. Together, our results identify CXXC5 as a novel epigenetic regulator for pDC-mediated antiviral response. |
format | Online Article Text |
id | pubmed-5413332 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-54133322017-11-01 Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs Ma, Shixin Wan, Xiaoling Deng, Zihou Shi, Lei Hao, Congfang Zhou, Zhenyuan Zhou, Chun Fang, Yiyuan Liu, Jinghua Yang, Jing Chen, Xia Li, Tiantian Zang, Aiping Yin, Shigang Li, Bin Plumas, Joel Chaperot, Laurence Zhang, Xiaoming Xu, Guoliang Jiang, Lubin Shen, Nan Xiong, Sidong Gao, Xiaoming Zhang, Yan Xiao, Hui J Exp Med Research Articles TLR7/9 signals are capable of mounting massive interferon (IFN) response in plasmacytoid dendritic cells (pDCs) immediately after viral infection, yet the involvement of epigenetic regulation in this process has not been documented. Here, we report that zinc finger CXXC family epigenetic regulator CXXC5 is highly expressed in pDCs, where it plays a crucial role in TLR7/9- and virus-induced IFN response. Notably, genetic ablation of CXXC5 resulted in aberrant methylation of the CpG-containing island (CGI) within the Irf7 gene and impaired IRF7 expression in steady-state pDCs. Mechanistically, CXXC5 is responsible for the recruitment of DNA demethylase Tet2 to maintain the hypomethylation of a subset of CGIs, a process coincident with active histone modifications and constitutive transcription of these CGI-containing genes. Consequently, CXXC5-deficient mice had compromised early IFN response and became highly vulnerable to infection by herpes simplex virus and vesicular stomatitis virus. Together, our results identify CXXC5 as a novel epigenetic regulator for pDC-mediated antiviral response. The Rockefeller University Press 2017-05-01 /pmc/articles/PMC5413332/ /pubmed/28416650 http://dx.doi.org/10.1084/jem.20161149 Text en © 2017 Ma et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Ma, Shixin Wan, Xiaoling Deng, Zihou Shi, Lei Hao, Congfang Zhou, Zhenyuan Zhou, Chun Fang, Yiyuan Liu, Jinghua Yang, Jing Chen, Xia Li, Tiantian Zang, Aiping Yin, Shigang Li, Bin Plumas, Joel Chaperot, Laurence Zhang, Xiaoming Xu, Guoliang Jiang, Lubin Shen, Nan Xiong, Sidong Gao, Xiaoming Zhang, Yan Xiao, Hui Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs |
title | Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs |
title_full | Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs |
title_fullStr | Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs |
title_full_unstemmed | Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs |
title_short | Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs |
title_sort | epigenetic regulator cxxc5 recruits dna demethylase tet2 to regulate tlr7/9-elicited ifn response in pdcs |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413332/ https://www.ncbi.nlm.nih.gov/pubmed/28416650 http://dx.doi.org/10.1084/jem.20161149 |
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