biostudies-literatureWang XNatural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation)National Natural Science Foundation of China (National Science Foundation of China)4529https://www.ebi.ac.uk/biostudies/studies/S-EPMC12081701biostudies-literatureUnknown16(1)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 Nature communicationsPRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub.PMC1208170131900132324705887232052Yao KChong HZhou QGuo YWan LFan MWang FLiu RYu DChen CLi LJia LSong JXue YLi XLu LHe YLin DXiang ZWang XHan JGao XSu WfalsePRMT3 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 2025-01-01T00:00:00Z2025 May2026-06-01T23:01:41.492Z2026-05-23T03:08:16.754ZS-EPMC120817014037460710.1038/s41467-025-59578-5