ArticleNucleic acids research2014
Bimodal high-affinity association of Brd4 with murine leukemia virus integrase and mononucleosomes.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Specialized DNA Structures Act as Genomic Beacons for Integration by Evolutionarily Diverse Retroviruses.Viruses · 2023Pooled it
- BRD4 binds the nucleosome via both histone and DNA interactions.Molecular cell · 2026Article
- Retroviral intasome architecture shapes the dynamics of target DNA search and integration.PLoS pathogens · 2026Article
- Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication.FEMS microbiology reviews · 2026Review
- The BRD4-nucleosome interaction is enhanced modestly and non-selectively by histone acetylation.Nucleic acids research · 2025Article
- BET Inhibitor JQ1 Attenuates Feline Leukemia Virus DNA, Provirus, and Antigen Production in Domestic Cat Cell Lines.Viruses · 2023Article
- GS-9822, a preclinical LEDGIN candidate, displays a block-and-lock phenotype in cell culture.Antimicrobial agents and chemotherapy · 2023Article
- BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications.Molecules (Basel, Switzerland) · 2023Review
- Delivering genes with human immunodeficiency virus-derived vehicles: still state-of-the-art after 25 years.Journal of biomedical science · 2022Review
- BET-Independent Murine Leukemia Virus Integration Is RetargetedMicrobiology spectrum · 2022Article
- Alternative Mechanisms for DNA Engagement by BET Bromodomain-Containing Proteins.Biochemistry · 2022Article
- Structure and function of retroviral integrase.Nature reviews. Microbiology · 2022Review
- Development of Murine Leukemia Virus Integrase-Derived Peptides That Bind Brd4 Extra-Terminal Domain as Candidates for Suppression of Acute Myeloid Leukemia.ACS pharmacology & translational science · 2021Article
- Rationally Designed ACE2-Derived Peptides Inhibit SARS-CoV-2.Bioconjugate chemistry · 2021Article
- Retroviral integrase: Structure, mechanism, and inhibition.The Enzymes · 2021Article
- Strategies for Targeting Retroviral Integration for Safer Gene Therapy: Advances and Challenges.Frontiers in molecular biosciences · 2021Review
- Aberrant activation of super enhancer and choline metabolism drive antiandrogen therapy resistance in prostate cancer.Oncogene · 2020Article
- Post-mitotic BET-induced reshaping of integrase quaternary structure supports wild-type MLV integration.Nucleic acids research · 2019Article
- Interactions between Retroviruses and the Host Cell Genome.Molecular therapy. Methods & clinical development · 2018Review
- The Short Isoform of BRD4 Promotes HIV-1 Latency by Engaging Repressive SWI/SNF Chromatin-Remodeling Complexes.Molecular cell · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The importance of understanding the molecular mechanisms of murine leukemia virus (MLV) integration into host chromatin is highlighted by the development of MLV-based vectors for human gene-therapy. We have recently identified BET proteins (Brd2, 3 and 4) as the main cellular binding partners of MLV integrase (IN) and demonstrated their significance for effective MLV integration at transcription start sites. Here we show that recombinant Brd4, a representative of the three BET proteins, establishes complementary high-affinity interactions with MLV IN and mononucleosomes (MNs). Brd4(1-720) but not its N- or C-terminal fragments effectively stimulate MLV IN strand transfer activities in vitro. Mass spectrometry- and NMR-based approaches have enabled us to map key interacting interfaces between the C-terminal domain of BRD4 and the C-terminal tail of MLV IN. Additionally, the N-terminal fragment of Brd4 binds to both DNA and acetylated histone peptides, allowing it to bind tightly to MNs. Comparative analyses of the distributions of various histone marks along chromatin revealed significant positive correlations between H3- and H4-acetylated histones, BET protein-binding sites and MLV-integration sites. Our findings reveal a bimodal mechanism for BET protein-mediated MLV integration into select chromatin locations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.