ArticleNucleic acids research2019
Post-mitotic BET-induced reshaping of integrase quaternary structure supports wild-type MLV integration.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Review
- BET-Independent Murine Leukemia Virus Integration Is RetargetedMicrobiology spectrum · 2022Article
- A common binding motif in the ET domain of BRD3 forms polymorphic structural interfaces with host and viral proteins.Structure (London, England : 1993) · 2021Article
- Capsid-Labelled HIV To Investigate the Role of Capsid during Nuclear Import and Integration.Journal of virology · 2020Article
- Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase.Nucleic acids research · 2019Article
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Moloney murine leukemia virus (MLV) is a prototype gammaretrovirus requiring nuclear disassembly before DNA integration. In the nucleus, integration site selection towards promoter/enhancer elements is mediated by the host factor bromo- and extraterminal domain (BET) proteins (bromodomain (Brd) proteins 2, 3 and 4). MLV-based retroviral vectors are used in gene therapy trials. In some trials leukemia occurred through integration of the MLV vector in close proximity to cellular oncogenes. BET-mediated integration is poorly understood and the nature of integrase oligomers heavily debated. Here, we created wild-type infectious MLV vectors natively incorporating fluorescent labeled IN and performed single-molecule intensity and Förster resonance energy transfer experiments. The nuclear localization of the MLV pre-integration complex neither altered the IN content, nor its quaternary structure. Instead, BET-mediated interaction of the MLV intasome with chromatin in the post-mitotic nucleus reshaped its quaternary structure.
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Registered trials
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