Evidence map›Paper›PMID 23818621›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

BET proteins promote efficient murine leukemia virus integration at transcription start sites.

Amit Sharma, Ross C Larue, Matthew R Plumb, Nirav Malani, Frances Male, Alison Slaughter, Jacques J Kessl, Nikolozi Shkriabai, Elizabeth Coward, Sriram S Aiyer and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed, 1 pooled it
13.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

127 citing papers in PubMed, 1 synthesis or guideline pooled it, 196 citations in OpenAlex.

  1. Pooled it
  2. Loop Plasticity Drives Paralog-Specific Recognition in BET ET Domains.Journal of chemical information and modeling · 2026
    Article
  3. Article
  4. Review
  5. Loop Plasticity Drives Paralog-Specific Recognition in BET ET Domains.bioRxiv : the preprint server for biology · 2025
    Article
  6. Article
  7. Designing molecules: directing stem cell differentiation.Frontiers in bioengineering and biotechnology · 2024
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Pseudotyped Viruses.Advances in experimental medicine and biology · 2023
    Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article

67 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Amit SharmaCenter for Retrovirus Research, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Ross C Larue
Matthew R Plumb
Nirav Malani
Frances Male
Alison Slaughter
Jacques J Kessl
Nikolozi Shkriabai
Elizabeth Coward
Sriram S Aiyer
Patrick L Green
Li Wu
Monica J Roth
Frederic D Bushman
Mamuka Kvaratskhelia
University of Pennsylvania · USRutgers, The State University of New Jersey · USThe Ohio State University · US

Funding

Role of Inflammation in Tax-mediated TumorigenesisP01CA100730 · NCI · WASHINGTON UNIVERSITY · PI Malachi Griffith · 2003 to 2026
$44.8M
Favored Sites for HIV Integration in the Human GenomeR01AI052845 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D · 2002 to 2017
$5.6M
Structure and function of HIV-1 integraseR01AI062520 · NIAID · UNIVERSITY OF COLORADO DENVER · PI KVARATSKHELIA, MAMUKA · 2006 to 2020
$5.3M
Integration of Murine Retroviral VectorsR01GM070837 · NIGMS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI ROTH, MONICA J. · 2005 to 2013
$2.1M
Retroviral Integration & HDAC inhibitorsR01GM088808 · NIGMS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI ROTH, MONICA J. · 2009 to 2012
$1.3M
NCI NIH HHS CA100730NCI NIH HHS P01 CA100730NIAID NIH HHS AI052845NIAID NIH HHS AI062520NIAID NIH HHS R01 AI052845NIAID NIH HHS R01 AI062520NIGMS NIH HHS GM070837NIGMS NIH HHS GM088808NIGMS NIH HHS R01 GM070837NIGMS NIH HHS R01 GM088808
6 · The paper itself

Abstract

The selection of chromosomal targets for retroviral integration varies markedly, tracking with the genus of the retrovirus, suggestive of targeting by binding to cellular factors. γ-Retroviral murine leukemia virus (MLV) DNA integration into the host genome is favored at transcription start sites, but the underlying mechanism for this preference is unknown. Here, we have identified bromodomain and extraterminal domain (BET) proteins (Brd2, -3, -4) as cellular-binding partners of MLV integrase. We show that purified recombinant Brd4(1-720) binds with high affinity to MLV integrase and stimulates correct concerted integration in vitro. JQ-1, a small molecule that selectively inhibits interactions of BET proteins with modified histone sites impaired MLV but not HIV-1 integration in infected cells. Comparison of the distribution of BET protein-binding sites analyzed using ChIP-Seq data and MLV-integration sites revealed significant positive correlations. Antagonism of BET proteins, via JQ-1 treatment or RNA interference, reduced MLV-integration frequencies at transcription start sites. These findings elucidate the importance of BET proteins for MLV integration efficiency and targeting and provide a route to developing safer MLV-based vectors for human gene therapy.

Indexed as

AnimalsAzepinesBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorChromatin ImmunoprecipitationHEK293 CellsHigh-Throughput Nucleotide SequencingHost-Pathogen InteractionsHumansIntegrasesLeukemia Virus, MurineMass SpectrometryMiceNIH 3T3 CellsNuclear ProteinsAzepinesBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsIntegrases(+)-JQ1 compoundNuclear ProteinsRecombinant ProteinsTranscription FactorsTriazolesretroviral gene therapyvirus–host interactions

Identifiers

PMID23818621
PMCPMC3718171
OpenAlexW1976477813

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.