Virus-human chromatin interactions reorganise 3D genome and hijack KDM5B for promoting metastasis in nasopharyngeal carcinoma
Abstract Epstein–Barr virus, the first identified human DNA tumour virus, is detectable in more than 90% of nasopharyngeal carcinoma patients in endemic regions. The 3D chromosome conformation analysis reveals that virus‒host chromatin interactions induce the spatial reorganisation of loops and comp...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61597-1 |
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| author | Dittman Lai-Shun Chung Zhaozheng Hou Ying Wang Kazi Anisha Islam Songran Liu Jiayan Liu Larry Ka-Yue Chow Yuki Yuk-Wun Wong Cyrus Paak-Ting Chak Yingpei Zhang Lanqi Gong Ziyang Qi Kiu-Wai Cheng Zhuoyou Yu Ping Feng Zilu Huang Roger Kai-Cheong Ngan Xinyuan Guan Wai-Tong Ng Zhonghua Liu Anna Chi-Man Tsang Dora Lai-Wan Kwong Anne Wing-Mui Lee Victor Ho-Fun Lee Honglin Chen Yunfei Xia Wei Dai |
| author_facet | Dittman Lai-Shun Chung Zhaozheng Hou Ying Wang Kazi Anisha Islam Songran Liu Jiayan Liu Larry Ka-Yue Chow Yuki Yuk-Wun Wong Cyrus Paak-Ting Chak Yingpei Zhang Lanqi Gong Ziyang Qi Kiu-Wai Cheng Zhuoyou Yu Ping Feng Zilu Huang Roger Kai-Cheong Ngan Xinyuan Guan Wai-Tong Ng Zhonghua Liu Anna Chi-Man Tsang Dora Lai-Wan Kwong Anne Wing-Mui Lee Victor Ho-Fun Lee Honglin Chen Yunfei Xia Wei Dai |
| author_sort | Dittman Lai-Shun Chung |
| collection | DOAJ |
| description | Abstract Epstein–Barr virus, the first identified human DNA tumour virus, is detectable in more than 90% of nasopharyngeal carcinoma patients in endemic regions. The 3D chromosome conformation analysis reveals that virus‒host chromatin interactions induce the spatial reorganisation of loops and compartments, resulting in “enhancer infestation” and switch of “H3K27 bivalency” at EBV-interacting regions. Through this mechanism, EBV hijacks KDM5B, a gatekeeper of genome stability, and its binding targets, leading to aberrant activation of an EBVIR-enhancer-KDM5B signature. Cancer cells with this signature present increased MYC activation, DNA damage responses, and epigenetic plasticity of epithelial-immune dual features with metastatic potential. Our multicentre multiomics study confirms that this signature is the prerequisite for chromosome instability and can be utilised as a risk factor for distant metastasis. This study highlights a mechanism in which latent viral episomes can alter the host high-order epigenotype, promoting transcriptional rewiring and metastasis in NPC. |
| format | Article |
| id | doaj-art-0d56b1eb26db4790b7e479641a2f9a0c |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0d56b1eb26db4790b7e479641a2f9a0c2025-08-20T03:43:00ZengNature PortfolioNature Communications2041-17232025-08-0116112110.1038/s41467-025-61597-1Virus-human chromatin interactions reorganise 3D genome and hijack KDM5B for promoting metastasis in nasopharyngeal carcinomaDittman Lai-Shun Chung0Zhaozheng Hou1Ying Wang2Kazi Anisha Islam3Songran Liu4Jiayan Liu5Larry Ka-Yue Chow6Yuki Yuk-Wun Wong7Cyrus Paak-Ting Chak8Yingpei Zhang9Lanqi Gong10Ziyang Qi11Kiu-Wai Cheng12Zhuoyou Yu13Ping Feng14Zilu Huang15Roger Kai-Cheong Ngan16Xinyuan Guan17Wai-Tong Ng18Zhonghua Liu19Anna Chi-Man Tsang20Dora Lai-Wan Kwong21Anne Wing-Mui Lee22Victor Ho-Fun Lee23Honglin Chen24Yunfei Xia25Wei Dai26Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, The Sun Yat-sen University Cancer CenterDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongCentre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology ParkDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Radiation Oncology, Sun Yat-sen University Cancer CentreDepartment of Radiation Oncology, Sun Yat-sen University Cancer CentreDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Biostatistics, Columbia UniversityDepartment of Anatomical and Cellular Pathology and State Key Laboratory of Translational Oncology, The Chinese University of Hong KongDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongCentre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology ParkState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, The Sun Yat-sen University Cancer CenterDepartment of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongAbstract Epstein–Barr virus, the first identified human DNA tumour virus, is detectable in more than 90% of nasopharyngeal carcinoma patients in endemic regions. The 3D chromosome conformation analysis reveals that virus‒host chromatin interactions induce the spatial reorganisation of loops and compartments, resulting in “enhancer infestation” and switch of “H3K27 bivalency” at EBV-interacting regions. Through this mechanism, EBV hijacks KDM5B, a gatekeeper of genome stability, and its binding targets, leading to aberrant activation of an EBVIR-enhancer-KDM5B signature. Cancer cells with this signature present increased MYC activation, DNA damage responses, and epigenetic plasticity of epithelial-immune dual features with metastatic potential. Our multicentre multiomics study confirms that this signature is the prerequisite for chromosome instability and can be utilised as a risk factor for distant metastasis. This study highlights a mechanism in which latent viral episomes can alter the host high-order epigenotype, promoting transcriptional rewiring and metastasis in NPC.https://doi.org/10.1038/s41467-025-61597-1 |
| spellingShingle | Dittman Lai-Shun Chung Zhaozheng Hou Ying Wang Kazi Anisha Islam Songran Liu Jiayan Liu Larry Ka-Yue Chow Yuki Yuk-Wun Wong Cyrus Paak-Ting Chak Yingpei Zhang Lanqi Gong Ziyang Qi Kiu-Wai Cheng Zhuoyou Yu Ping Feng Zilu Huang Roger Kai-Cheong Ngan Xinyuan Guan Wai-Tong Ng Zhonghua Liu Anna Chi-Man Tsang Dora Lai-Wan Kwong Anne Wing-Mui Lee Victor Ho-Fun Lee Honglin Chen Yunfei Xia Wei Dai Virus-human chromatin interactions reorganise 3D genome and hijack KDM5B for promoting metastasis in nasopharyngeal carcinoma Nature Communications |
| title | Virus-human chromatin interactions reorganise 3D genome and hijack KDM5B for promoting metastasis in nasopharyngeal carcinoma |
| title_full | Virus-human chromatin interactions reorganise 3D genome and hijack KDM5B for promoting metastasis in nasopharyngeal carcinoma |
| title_fullStr | Virus-human chromatin interactions reorganise 3D genome and hijack KDM5B for promoting metastasis in nasopharyngeal carcinoma |
| title_full_unstemmed | Virus-human chromatin interactions reorganise 3D genome and hijack KDM5B for promoting metastasis in nasopharyngeal carcinoma |
| title_short | Virus-human chromatin interactions reorganise 3D genome and hijack KDM5B for promoting metastasis in nasopharyngeal carcinoma |
| title_sort | virus human chromatin interactions reorganise 3d genome and hijack kdm5b for promoting metastasis in nasopharyngeal carcinoma |
| url | https://doi.org/10.1038/s41467-025-61597-1 |
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