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
{"title":"PRMT3通过增加染色质可及性来逆转HIV-1潜伏期,形成含有tead4 - p - tefb的转录中心","authors":"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","doi":"10.1038/s41467-025-59578-5","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"77 1","pages":""},"PeriodicalIF":14.7000,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub\",\"authors\":\"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\",\"doi\":\"10.1038/s41467-025-59578-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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.</p>\",\"PeriodicalId\":19066,\"journal\":{\"name\":\"Nature Communications\",\"volume\":\"77 1\",\"pages\":\"\"},\"PeriodicalIF\":14.7000,\"publicationDate\":\"2025-05-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Communications\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1038/s41467-025-59578-5\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-025-59578-5","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub
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.
期刊介绍:
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.