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.
Authors
- Xiang Gao (ORCID: https://orcid.org/0000-0002-3774-1852)
- Zixun Xiang
- Yuxian He (ORCID: https://orcid.org/0000-0003-2048-6696)
- Lei Jia (ORCID: https://orcid.org/0000-0003-3721-1998)
- Qiang Zhou (ORCID: https://orcid.org/0000-0001-7202-3947)
- Rongdiao Liu (ORCID: https://orcid.org/0000-0002-3802-3561)
- Yuhua Xue (ORCID: https://orcid.org/0000-0001-5804-5162)
- Wen Su (ORCID: https://orcid.org/0000-0002-2248-7361)
- Yafei Guo (ORCID: https://orcid.org/0000-0002-8054-1856)
- Dan Yu (ORCID: https://orcid.org/0000-0003-3488-0467)
- Jingwan Han
- Huihui Chong (ORCID: https://orcid.org/0000-0001-6965-2742)
- Dandan Lin (ORCID: https://orcid.org/0000-0003-3843-6945)
- Chunjing Chen (ORCID: https://orcid.org/0009-0009-1270-6530)
- Jin‐Wen Song (ORCID: https://orcid.org/0000-0002-8582-8012)
- Xinyu Wang (ORCID: https://orcid.org/0000-0002-6248-9601)
- Lin Li (ORCID: https://orcid.org/0000-0001-6124-5237)
- Fu‐Sheng Wang (ORCID: https://orcid.org/0000-0002-8043-6685)
- Li Xu (ORCID: https://orcid.org/0000-0003-3255-326X)
- Kaihu Yao (ORCID: https://orcid.org/0000-0002-4747-8920)
- Lu Lü (ORCID: https://orcid.org/0000-0002-8290-8834)
- Miao Fan
- Leilei Wan
Institutions
- University of Science and Technology of China (CN)
- Xiamen University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Wenzhou Medical University (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- Academy of Military Medical Sciences (CN)
- Chinese PLA General Hospital (CN)
- Hong Kong Virtual University (CN)
- China Academy of Chinese Medical Sciences (CN)
- Beijing Children’s Hospital (CN)
- Hohhot First Hospital (CN)
- University of Hong Kong (HK)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-15
- DOI
- https://doi.org/10.1038/s41467-025-59578-5
- Citations
- 4
- Primary Topic
- Cancer-related gene regulation
- Type
- article
- Field-Weighted Citation Impact
- 3.22
Funders
- National Natural Science Foundation of China
- Capital Medical University
- Beijing Municipal Health Commission