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PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub

Author

Listed:
  • Xinyu Wang

    (National Center for Children’s Health)

  • Yuhua Xue

    (Xiamen University)

  • Lin Li

    (Academy of Military Medical Sciences)

  • Jinwen Song

    (National Clinical Research Center for Infectious Diseases)

  • Lei Jia

    (Academy of Military Medical Sciences)

  • Xu Li

    (The First Hospital of Hohhot)

  • Miao Fan

    (National Center for Children’s Health)

  • Lu Lu

    (National Center for Children’s Health
    Xiamen University)

  • Wen Su

    (National Center for Children’s Health)

  • Jingwan Han

    (Academy of Military Medical Sciences)

  • Dandan Lin

    (Academy of Military Medical Sciences)

  • Rongdiao Liu

    (Xiamen University
    Wenzhou Medical University)

  • Xiang Gao

    (Xiamen University)

  • Yafei Guo

    (Xiamen University)

  • Zixun Xiang

    (Xiamen University)

  • Chunjing Chen

    (Xiamen University)

  • Linyu Wan

    (University of Science and Technology of China)

  • Huihui Chong

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Yuxian He

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Fusheng Wang

    (National Clinical Research Center for Infectious Diseases)

  • Kaihu Yao

    (National Center for Children’s Health)

  • Qiang Zhou

    (The University of Hong Kong)

  • Dan Yu

    (National Center for Children’s Health
    Chinese Institutes for Medical Research)

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.

Suggested Citation

  • 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 , 2025. "PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59578-5
    DOI: 10.1038/s41467-025-59578-5
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    References listed on IDEAS

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    1. Iain C. Clark & Prakriti Mudvari & Shravan Thaploo & Samuel Smith & Mohammad Abu-Laban & Mehdi Hamouda & Marc Theberge & Sakshi Shah & Sung Hee Ko & Liliana Pérez & Daniel G. Bunis & James S. Lee & Di, 2023. "HIV silencing and cell survival signatures in infected T cell reservoirs," Nature, Nature, vol. 614(7947), pages 318-325, February.
    2. Xiang-Hong Ran & Jia-Wu Zhu & Run-Ze Ni & Yong-Tang Zheng & Ya-Yun Chen & Wei-Hua Zheng & Dan Mu, 2023. "TRIM5α recruits HDAC1 to p50 and Sp1 and promotes H3K9 deacetylation at the HIV-1 LTR," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
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