Evidence map›Paper›PMID 35902886›Full record

ArticleClinical epigenetics2022

Distinct modulation of IFNγ-induced transcription by BET bromodomain and catalytic P300/CBP inhibition in breast cancer.

Simon J Hogg, Olga Motorna, Conor J Kearney, Emily B Derrick, Imran G House, Izabela Todorovski, Madison J Kelly, Magnus Zethoven, Kenneth D Bromberg, Albert Lai and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 45% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. 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

14 authors at 4 institutions in 2 countries.

Simon J Hogg *Gene Regulation Laboratory, Peter MacCallum Cancer Center, 305 Grattan Street, Melbourne, VIC, 3000, Australia.
Olga Motorna *Gene Regulation Laboratory, Peter MacCallum Cancer Center, 305 Grattan Street, Melbourne, VIC, 3000, Australia.
Conor J KearneyGene Regulation Laboratory, Peter MacCallum Cancer Center, 305 Grattan Street, Melbourne, VIC, 3000, Australia.
Emily B DerrickSir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia.
Imran G HouseSir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia.
Izabela TodorovskiGene Regulation Laboratory, Peter MacCallum Cancer Center, 305 Grattan Street, Melbourne, VIC, 3000, Australia.
Madison J KellyGene Regulation Laboratory, Peter MacCallum Cancer Center, 305 Grattan Street, Melbourne, VIC, 3000, Australia.
Magnus ZethovenGene Regulation Laboratory, Peter MacCallum Cancer Center, 305 Grattan Street, Melbourne, VIC, 3000, Australia.
Kenneth D BrombergOncology Discovery, AbbVie, North Chicago, IL, USA.
Albert LaiOncology Discovery, AbbVie, North Chicago, IL, USA.
Paul A BeavisSir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia.
Jake ShorttSir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia.
Ricky W Johnstone *Gene Regulation Laboratory, Peter MacCallum Cancer Center, 305 Grattan Street, Melbourne, VIC, 3000, Australia. Ricky.johnstone@petermac.org.
Stephin J Vervoort *Gene Regulation Laboratory, Peter MacCallum Cancer Center, 305 Grattan Street, Melbourne, VIC, 3000, Australia. vervoort.s@wehi.edu.au.
Peter MacCallum Cancer Centre · AUUniversity of Melbourne · AUAbbVie (United States) · USMonash Health · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundInterferon gamma (IFNγ) is a pro-inflammatory cytokine that directly activates the JAK/STAT pathway. However, the temporal dynamics of chromatin remodeling and transcriptional activation initiated by IFNγ have not been systematically profiled in an unbiased manner. Herein, we integrated transcriptomic and epigenomic profiling to characterize the acute epigenetic changes induced by IFNγ stimulation in a murine breast cancer model.

resultsWe identified de novo activation of cis-regulatory elements bound by Irf1 that were characterized by increased chromatin accessibility, differential usage of pro-inflammatory enhancers, and downstream recruitment of BET proteins and RNA polymerase II. To functionally validate this hierarchical model of IFNγ-driven transcription, we applied selective antagonists of histone acetyltransferases P300/CBP or acetyl-lysine readers of the BET family. This highlighted that histone acetylation is an antecedent event in IFNγ-driven transcription, whereby targeting of P300/CBP acetyltransferase activity but not BET inhibition could curtail the epigenetic remodeling induced by IFNγ through suppression of Irf1 transactivation.

conclusionsThese data highlight the ability for epigenetic therapies to reprogram pro-inflammatory gene expression, which may have therapeutic implications for anti-tumor immunity and inflammatory diseases.

Indexed as

Breast NeoplasmsInterferon-gammaAcetylationAnimalsDNA MethylationE1A-Associated p300 ProteinFemaleJanus KinasesMembrane ProteinsMicePhosphoproteinsSignal TransductionSTAT Transcription FactorsE1A-Associated p300 ProteinInterferon-gammaJanus KinasesMembrane ProteinsPhosphoproteinsSTAT Transcription FactorsBromodomainEnhancerH3k27acHistone acetylationImmuno-oncologyInflammationInterferonP300/CBP

Identifiers

PMID35902886
PMCPMC9336046
OpenAlexW4288430604

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.