Evidence map›Paper›PMID 28733670›Full record

ArticleScientific reports2017

BRD3 and BRD4 BET Bromodomain Proteins Differentially Regulate Skeletal Myogenesis.

Thomas C Roberts, Usue Etxaniz, Alessandra Dall'Agnese, Shwu-Yuan Wu, Cheng-Ming Chiang, Paul E Brennan, Matthew J A Wood, Pier Lorenzo Puri

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

32 citing papers in PubMed, 44 citations in OpenAlex.

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  15. An interplay between BRD4 and G9a regulates skeletal myogenesis.Frontiers in cell and developmental biology · 2022
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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

8 authors at 5 institutions in 3 countries.

Thomas C RobertsSanford Burnham Prebys Medical Discovery Institute, Development, Aging and Regeneration Program, La Jolla, CA, 92037, USA. thomas.roberts@dpag.ox.ac.uk.
Usue EtxanizSanford Burnham Prebys Medical Discovery Institute, Development, Aging and Regeneration Program, La Jolla, CA, 92037, USA.
Alessandra Dall'AgneseSanford Burnham Prebys Medical Discovery Institute, Development, Aging and Regeneration Program, La Jolla, CA, 92037, USA.
Shwu-Yuan WuSimmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas, 75390, USA.
Cheng-Ming ChiangSimmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas, 75390, USA.
Paul E BrennanStructural Genomics Consortium and Target Discovery Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7DQ, UK.
Matthew J A WoodDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK.
Pier Lorenzo PuriSanford Burnham Prebys Medical Discovery Institute, Development, Aging and Regeneration Program, La Jolla, CA, 92037, USA. lpuri@sbpdiscovery.org.
Sanford Burnham Prebys Medical Discovery Institute · USThe University of Texas Southwestern Medical Center · USUniversity of Oxford · GBDiscovery Institute · USFondazione Santa Lucia · IT

Funding

Pathogenic Alterations of the 3D Epigenetic Landscape in Dystrophin-Deficient Skeletal Muscles and Reversal by Dystrophin Re-ExpressionR01AR056712 · NIAMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Pier Lorenzo Puri · 2009 to 2026
$7.3M
Signal-dependent switch of SWI/SNF by miRNAs & control of muscle stem cell fateR01AR052779 · NIAMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI PURI, PIER LORENZO · 2006 to 2015
$4.1M
E2-Cellular Complexes in HPV Chromatin TranscriptionR01CA103867 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI CHIANG, CHENG-MING · 2004 to 2017
$4.0M
San Diego Skeletal Muscle Research CenterP30AR061303 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, JU · 2011 to 2015
$3.3M
Medical Research Council MC_PC_15029Medical Research Council MR/P003125/1NCI NIH HHS R01 CA103867NIAMS NIH HHS P30 AR061303NIAMS NIH HHS R01 AR052779NIAMS NIH HHS R01 AR056712Wellcome Trust
6 · The paper itself

Abstract

Myogenic differentiation proceeds through a highly coordinated cascade of gene activation that necessitates epigenomic changes in chromatin structure. Using a screen of small molecule epigenetic probes we identified three compounds which inhibited myogenic differentiation in C2C12 myoblasts; (+)-JQ1, PFI-1, and Bromosporine. These molecules target Bromodomain and Extra Terminal domain (BET) proteins, which are epigenetic readers of acetylated histone lysine tail residues. BETi-mediated anti-myogenic effects were also observed in a model of MYOD1-mediated myogenic conversion of human fibroblasts, and in primary mouse and human myoblasts. All three BET proteins BRD2, BRD3 and BRD4 exhibited distinct and dynamic patterns of protein expression over the course of differentiation without concomitant changes in mRNA levels, suggesting that BET proteins are regulated at the post-transcriptional level. Specific BET protein knockdown by RNA interference revealed that BRD4 was required for myogenic differentiation, whereas BRD3 down-regulation resulted in enhanced myogenic differentiation. ChIP experiments revealed a preferential binding of BRD4 to the Myog promoter during C2C12 myoblast differentiation, co-incident with increased levels of H3K27 acetylation. These results have identified an essential role for BET proteins in the regulation of skeletal myogenesis, and assign distinct functions to BRD3 and BRD4.

Indexed as

Muscle DevelopmentAnimalsAzepinesBromodomain Containing ProteinsCell DifferentiationCell LineEpigenesis, GeneticGene Expression Regulation, DevelopmentalHistonesHumansMiceMyoblasts, SkeletalMyogeninNuclear ProteinsPromoter Regions, GeneticTranscription FactorsAzepinesBrd3 protein, mouseBrd4 protein, mouseBromodomain Containing ProteinsHistones(+)-JQ1 compoundMyogeninMyog protein, mouseNuclear ProteinsTranscription FactorsTriazoles

Identifiers

PMID28733670
PMCPMC5522382
OpenAlexW2735274295

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.