ArticleScience advances2020
Competition between PAF1 and MLL1/COMPASS confers the opposing function of LEDGF/p75 in HIV latency and proviral reactivation.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 23 citations in OpenAlex.
- The HIV-1 restriction factor RPRD2 does not inhibit transcription of HIV-1 or endogenous retroelements.bioRxiv : the preprint server for biology · 2026Article
- Structure and function of IWS1 in transcription elongation.Nucleic acids research · 2026Article
- HIV-1 Tat: Molecular Switch in Viral Persistence and Emerging Technologies for Functional Cure.International journal of molecular sciences · 2025Review
- HIV-1 latency: From acquaintance to confidant.Journal of virus eradication · 2025Review
- PSIP1 promotes gefitinib resistance in lung adenocarcinoma by inducing the expression of WASF3 and its downstream ITGB3/AKT signaling.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- The HIV-1 Transcriptional Program: From Initiation to Elongation Control.Journal of molecular biology · 2025Review
- Release of P-TEFb from the Super Elongation Complex promotes HIV-1 latency reversal.PLoS pathogens · 2024Article
- Release of P-TEFb from the Super Elongation Complex promotes HIV-1 latency reversal.bioRxiv : the preprint server for biology · 2024Article
- Review
- Premature transcription termination complex proteins PCF11 and WDR82 silence HIV-1 expression in latently infected cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- PRMT2 promotes HIV-1 latency by preventing nucleolar exit and phase separation of Tat into the Super Elongation Complex.Nature communications · 2023Article
- PRMT3 regulates the progression of invasive micropapillary carcinoma of the breast.Cancer science · 2023Article
- Review
- Enhancing HIV-1 latency reversal through regulating the elongating RNA Pol II pause-release by a small-molecule disruptor of PAF1C.Science advances · 2023Article
- Article
- Review
- Coordinated regulation of RNA polymerase II pausing and elongation progression by PAF1.Science advances · 2022Article
- Transcription Pause and Escape in Neurodevelopmental Disorders.Frontiers in neuroscience · 2022Review
- Insights Into Persistent HIV-1 Infection and Functional Cure: Novel Capabilities and Strategies.Frontiers in microbiology · 2022Review
- Viruses in the Nucleus.Cold Spring Harbor perspectives in biology · 2021Review
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcriptional status determines the HIV replicative state in infected patients. However, the transcriptional mechanisms for proviral replication control remain unclear. In this study, we show that, apart from its function in HIV integration, LEDGF/p75 differentially regulates HIV transcription in latency and proviral reactivation. During latency, LEDGF/p75 suppresses proviral transcription via promoter-proximal pausing of RNA polymerase II (Pol II) by recruiting PAF1 complex to the provirus. Following latency reversal, MLL1 complex competitively displaces PAF1 from the provirus through casein kinase II (CKII)-dependent association with LEDGF/p75. Depleting or pharmacologically inhibiting CKII prevents PAF1 dissociation and abrogates the recruitment of both MLL1 and Super Elongation Complex (SEC) to the provirus, thereby impairing transcriptional reactivation for latency reversal. These findings, therefore, provide a mechanistic understanding of how LEDGF/p75 coordinates its distinct regulatory functions at different stages of the post-integrated HIV life cycles. Targeting these mechanisms may have a therapeutic potential to eradicate HIV infection.
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