Evidence map›Paper›PMID 28588073›Full record

ArticleEMBO reports2017

Brd4-Brd2 isoform switching coordinates pluripotent exit and Smad2-dependent lineage specification.

Rosalia Fernandez-Alonso, Lindsay Davidson, Jens Hukelmann, Michael Zengerle, Alan R Prescott, Angus Lamond, Alessio Ciulli, Gopal P Sapkota, Greg M Findlay

Open access · hybridAbstract read
In one paragraph

Article in EMBO reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

20 citing papers in PubMed, 30 citations in OpenAlex.

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  8. Zebrafish ParalogsJournal of developmental biology · 2021
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  11. Review
  12. Article
  13. Article
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  15. Article
  16. Bromodomain Protein BRD4 Is Essential for Hair Cell Function and Survival.Frontiers in cell and developmental biology · 2020
    Article
  17. Article
  18. Article
  19. Article
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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

9 authors at 1 institution in 1 country.

Rosalia Fernandez-AlonsoThe MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, The University of Dundee, Dundee, UK.
Lindsay DavidsonPluripotent Stem Cell Facility, School of Life Sciences, The University of Dundee, Dundee, UK.
Jens HukelmannCentre for Gene Regulation and Expression, School of Life Sciences, The University of Dundee, Dundee, UK.
Michael ZengerleBiological Chemistry and Drug Discovery, School of Life Sciences, The University of Dundee, Dundee, UK.
Alan R PrescottCentre for Gene Regulation and Expression, School of Life Sciences, The University of Dundee, Dundee, UK.
Angus LamondCentre for Gene Regulation and Expression, School of Life Sciences, The University of Dundee, Dundee, UK.ORCID 0000-0001-6204-6045
Alessio CiulliBiological Chemistry and Drug Discovery, School of Life Sciences, The University of Dundee, Dundee, UK.
Gopal P SapkotaThe MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, The University of Dundee, Dundee, UK.
Greg M FindlayThe MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, The University of Dundee, Dundee, UK g.m.findlay@dundee.ac.uk.ORCID 0000-0002-7222-4965
University of Dundee · GB

Funding

European Research Council 311460Medical Research Council MC_UU_12016/3Medical Research Council MR/N000609/1
6 · The paper itself

Abstract

Pluripotent stem cells (PSCs) hold great clinical potential, as they possess the capacity to differentiate into fully specialised tissues such as pancreas, liver, neurons and cardiac muscle. However, the molecular mechanisms that coordinate pluripotent exit with lineage specification remain poorly understood. To address this question, we perform a small molecule screen to systematically identify novel regulators of the Smad2 signalling network, a key determinant of PSC fate. We reveal an essential function for BET family bromodomain proteins in Smad2 activation, distinct from the role of Brd4 in pluripotency maintenance. Mechanistically, BET proteins specifically engage Nodal gene regulatory elements (NREs) to promote Nodal signalling and Smad2 developmental responses. In pluripotent cells, Brd2-Brd4 occupy NREs, but only Brd4 is required for pluripotency gene expression. Brd4 downregulation facilitates pluripotent exit and drives enhanced Brd2 NRE occupancy, thereby unveiling a specific function for Brd2 in differentiative Nodal-Smad2 signalling. Therefore, distinct BET functionalities and Brd4-Brd2 isoform switching at NREs coordinate pluripotent exit with lineage specification.

Indexed as

Cell DifferentiationAnimalsBromodomain Containing ProteinsCell Cycle ProteinsCell LineCell LineageHumansMiceNuclear ProteinsPluripotent Stem CellsProteinsProtein Serine-Threonine KinasesSignal TransductionSmad2 ProteinTranscription FactorsBRD2 protein, humanBRD4 protein, humanbromodomain and extra-terminal domain protein, humanBromodomain Containing ProteinsCell Cycle ProteinsNuclear ProteinsProteinsProtein Serine-Threonine KinasesSmad2 ProteinSMAD2 protein, humanTranscription FactorsBET Bromodomaindifferentiationembryonic stem cellNodal‐Smad2 signallingPluripotency

Identifiers

PMID28588073
PMCPMC5494510
OpenAlexW2623786436

What OpenQuestion 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 OpenQuestion graph.