PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub
Abstract Latent HIV-1 presents a formidable challenge for viral eradication. HIV-1 transcription and latency reversal require interactions between the viral promoter and host proteins. Here, we perform the dCas9-targeted locus-specific protein analysis and discover the interaction of human arginine...
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| Format: | Article |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59578-5 |
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| author | Xinyu Wang Yuhua Xue Lin Li Jinwen Song Lei Jia Xu Li Miao Fan Lu Lu Wen Su Jingwan Han Dandan Lin Rongdiao Liu Xiang Gao Yafei Guo Zixun Xiang Chunjing Chen Linyu Wan Huihui Chong Yuxian He Fusheng Wang Kaihu Yao Qiang Zhou Dan Yu |
| author_facet | Xinyu Wang Yuhua Xue Lin Li Jinwen Song Lei Jia Xu Li Miao Fan Lu Lu Wen Su Jingwan Han Dandan Lin Rongdiao Liu Xiang Gao Yafei Guo Zixun Xiang Chunjing Chen Linyu Wan Huihui Chong Yuxian He Fusheng Wang Kaihu Yao Qiang Zhou Dan Yu |
| author_sort | Xinyu Wang |
| collection | DOAJ |
| description | Abstract Latent HIV-1 presents a formidable challenge for viral eradication. HIV-1 transcription and latency reversal require interactions between the viral promoter and host proteins. Here, we perform the dCas9-targeted locus-specific protein analysis and discover the interaction of human arginine methyltransferase 3 (PRMT3) with the HIV-1 promoter. This interaction reverses latency in cell line models and primary cells from latently infected persons by increasing the levels of H4R3Me2a and transcription factor P-TEFb at the viral promoter. PRMT3 is found to promote chromatin accessibility and transcription of HIV-1 and a small subset of host genes in regions harboring the classical recognition motif for another transcription factor TEAD4. This motif attracts TEAD4 and PRMT3 to the viral promoter to synergistically activate transcription. Physical interactions among PRMT3, P-TEFb, and TEAD4 exist, which may help form a transcriptional hub at the viral promoter. Our study reveals the potential of targeting these hub proteins to eradicate latent HIV-1. |
| format | Article |
| id | doaj-art-1e295f0cd50c441f9da7b5daf0c210a1 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-1e295f0cd50c441f9da7b5daf0c210a12025-08-20T03:48:06ZengNature PortfolioNature Communications2041-17232025-05-0116111810.1038/s41467-025-59578-5PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hubXinyu Wang0Yuhua Xue1Lin Li2Jinwen Song3Lei Jia4Xu Li5Miao Fan6Lu Lu7Wen Su8Jingwan Han9Dandan Lin10Rongdiao Liu11Xiang Gao12Yafei Guo13Zixun Xiang14Chunjing Chen15Linyu Wan16Huihui Chong17Yuxian He18Fusheng Wang19Kaihu Yao20Qiang Zhou21Dan Yu22Laboratory of Infection and Microbiology, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s HealthState Key Laboratory of Vaccines for Infectious Diseases, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiang An Biomedicine Laboratory, Affiliated Xiamen Eye Center, Xiamen UniversityState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesDepartment of Dermatology, The First Hospital of HohhotLaboratory of Infection and Microbiology, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s HealthLaboratory of Infection and Microbiology, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s HealthLaboratory of Infection and Microbiology, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s HealthState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesState Key Laboratory of Vaccines for Infectious Diseases, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiang An Biomedicine Laboratory, Affiliated Xiamen Eye Center, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiang An Biomedicine Laboratory, Affiliated Xiamen Eye Center, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiang An Biomedicine Laboratory, Affiliated Xiamen Eye Center, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiang An Biomedicine Laboratory, Affiliated Xiamen Eye Center, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiang An Biomedicine Laboratory, Affiliated Xiamen Eye Center, Xiamen UniversityThe First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of ChinaNHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical CollegeSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesLaboratory of Infection and Microbiology, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s HealthSchool of Biological Sciences, Faculty of Science, The University of Hong KongLaboratory of Infection and Microbiology, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s HealthAbstract Latent HIV-1 presents a formidable challenge for viral eradication. HIV-1 transcription and latency reversal require interactions between the viral promoter and host proteins. Here, we perform the dCas9-targeted locus-specific protein analysis and discover the interaction of human arginine methyltransferase 3 (PRMT3) with the HIV-1 promoter. This interaction reverses latency in cell line models and primary cells from latently infected persons by increasing the levels of H4R3Me2a and transcription factor P-TEFb at the viral promoter. PRMT3 is found to promote chromatin accessibility and transcription of HIV-1 and a small subset of host genes in regions harboring the classical recognition motif for another transcription factor TEAD4. This motif attracts TEAD4 and PRMT3 to the viral promoter to synergistically activate transcription. Physical interactions among PRMT3, P-TEFb, and TEAD4 exist, which may help form a transcriptional hub at the viral promoter. Our study reveals the potential of targeting these hub proteins to eradicate latent HIV-1.https://doi.org/10.1038/s41467-025-59578-5 |
| spellingShingle | Xinyu Wang Yuhua Xue Lin Li Jinwen Song Lei Jia Xu Li Miao Fan Lu Lu Wen Su Jingwan Han Dandan Lin Rongdiao Liu Xiang Gao Yafei Guo Zixun Xiang Chunjing Chen Linyu Wan Huihui Chong Yuxian He Fusheng Wang Kaihu Yao Qiang Zhou Dan Yu PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub Nature Communications |
| title | PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub |
| title_full | PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub |
| title_fullStr | PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub |
| title_full_unstemmed | PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub |
| title_short | PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub |
| title_sort | prmt3 reverses hiv 1 latency by increasing chromatin accessibility to form a tead4 p tefb containing transcriptional hub |
| url | https://doi.org/10.1038/s41467-025-59578-5 |
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