Evidence map›Paper›PMID 27536004›Full record

ArticleNucleic acids research2017

The bromodomain protein BRD4 regulates splicing during heat shock.

Michelle Hussong, Christian Kaehler, Martin Kerick, Christina Grimm, Alexandra Franz, Bernd Timmermann, Franziska Welzel, Jörg Isensee, Tim Hucho, Sylvia Krobitsch and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

40 citing papers in PubMed, 63 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. CLK2 Condensates Reorganize Nuclear Speckles and Induce Intron Retention.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. BRD4 as a Therapeutic Target in Pulmonary Diseases.International journal of molecular sciences · 2023
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

11 authors at 3 institutions in 1 country.

Michelle HussongDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestr.63-73, 14195 Berlin, Germany.
Christian KaehlerDepartment of Biology, Chemistry and Pharmacy, Free University Berlin, 14195 Berlin, Germany.
Martin KerickDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestr.63-73, 14195 Berlin, Germany.
Christina GrimmFunctional Epigenomics, CCG, Medical Faculty, University of Cologne, Weyertal 115b, 50931 Cologne, Germany.
Alexandra FranzDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestr.63-73, 14195 Berlin, Germany.
Bernd TimmermannSequencing Core Facility, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195 Berlin, Germany.
Franziska WelzelOtto-Warburg Laboratory 'Neurodegenerative disorders', Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195 Berlin, Germany.
Jörg IsenseeDepartment of Anesthesiology and Intensive Care Medicine, Experimental Anesthesiology and Pain Research, University of Cologne, 50931 Cologne, Germany.
Tim HuchoDepartment of Anesthesiology and Intensive Care Medicine, Experimental Anesthesiology and Pain Research, University of Cologne, 50931 Cologne, Germany.
Sylvia KrobitschOtto-Warburg Laboratory 'Neurodegenerative disorders', Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, 14195 Berlin, Germany.
Michal R SchweigerDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestr.63-73, 14195 Berlin, Germany mschweig@uni-koeln.de.
Max Planck Institute for Molecular Genetics · DEUniversity of Cologne · DEEpigenomics (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The cellular response to heat stress is an ancient and evolutionarily highly conserved defence mechanism characterised by the transcriptional up-regulation of cyto-protective genes and a partial inhibition of splicing. These features closely resemble the proteotoxic stress response during tumor development. The bromodomain protein BRD4 has been identified as an integral member of the oxidative stress as well as of the inflammatory response, mainly due to its role in the transcriptional regulation process. In addition, there are also several lines of evidence implicating BRD4 in the splicing process. Using RNA-sequencing we found a significant increase in splicing inhibition, in particular intron retentions (IR), following heat treatment in BRD4-depleted cells. This leads to a decrease of mRNA abundancy of the affected transcripts, most likely due to premature termination codons. Subsequent experiments revealed that BRD4 interacts with the heat shock factor 1 (HSF1) such that under heat stress BRD4 is recruited to nuclear stress bodies and non-coding SatIII RNA transcripts are up-regulated. These findings implicate BRD4 as an important regulator of splicing during heat stress. Our data which links BRD4 to the stress induced splicing process may provide novel mechanisms of BRD4 inhibitors in regard to anti-cancer therapies.

Indexed as

RNA SplicingBromodomain Containing ProteinsDNA-Binding ProteinsExonsHeat-Shock ResponseHeat Shock Transcription FactorsHeLa CellsHistone AcetyltransferasesHistone ChaperonesHot TemperatureHumansIntronsNuclear ProteinsProtein DomainsRNA, MessengerRNA, UntranslatedBRD1 protein, humanBromodomain Containing ProteinsDNA-Binding ProteinsHeat Shock Transcription FactorsHistone AcetyltransferasesHistone ChaperonesHSF1 protein, humanNuclear ProteinsRNA, MessengerRNA, UntranslatedTranscription Factors

Identifiers

PMID27536004
PMCPMC5224492
OpenAlexW2511307267

What OpenQuestion holds

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LicenceCC BY-NC
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.