Evidence map›Paper›PMID 27518902›Full record

ArticlePloS one2016

HIRA Is Required for Heart Development and Directly Regulates Tnni2 and Tnnt3.

Daniel Dilg, Rasha Noureldin M Saleh, Sarah Elizabeth Lee Phelps, Yoann Rose, Laurent Dupays, Cian Murphy, Timothy Mohun, Robert H Anderson, Peter J Scambler, Ariane L A Chapgier

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

21 citing papers in PubMed, 35 citations in OpenAlex.

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  4. Novel Silent Mutations in theAnimals : an open access journal from MDPI · 2025
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  10. Histone Chaperones as Cardinal Players in Development.Frontiers in cell and developmental biology · 2022
    Review
  11. Article
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  13. Article
  14. Cell Fate Decisions in the Wake of Histone H3 Deposition.Frontiers in cell and developmental biology · 2021
    Review
  15. Molecular genetics of 22q11.2 deletion syndrome.American journal of medical genetics. Part A · 2018
    Review
  16. Article
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  20. Review
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

10 authors at 4 institutions in 2 countries.

Daniel DilgDevelopmental Biology of Birth Defects Section, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, United Kingdom.
Rasha Noureldin M SalehDevelopmental Biology of Birth Defects Section, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, United Kingdom.
Sarah Elizabeth Lee PhelpsDevelopmental Biology of Birth Defects Section, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, United Kingdom.
Yoann RoseDevelopmental Biology of Birth Defects Section, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, United Kingdom.
Laurent DupaysThe Francis Crick Institute, Mill Hill Laboratory, the Ridgeway, Mill Hill, London NW7 1AA, United Kingdom.
Cian MurphyUCL Genetics Institute (UGI) Department of Genetics, Environment and Evolution University College London, Gower St, London WC1E 6BT, United Kingdom.
Timothy MohunFaculty of Medicine, Alexandria University, El-Gaish Rd, Alexandria, Egypt.
Robert H AndersonInstitute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ, United Kingdom.
Peter J ScamblerDevelopmental Biology of Birth Defects Section, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, United Kingdom.
Ariane L A ChapgierDevelopmental Biology of Birth Defects Section, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, United Kingdom.
University College London · GBAlexandria University · EGCentre for Life · GBThe Francis Crick Institute · GB

Funding

Biotechnology and Biological Sciences Research Council BB/E009603/1British Heart Foundation RG/15/14/31880Wellcome Trust
6 · The paper itself

Abstract

Chromatin remodelling is essential for cardiac development. Interestingly, the role of histone chaperones has not been investigated in this regard. HIRA is a member of the HUCA (HIRA/UBN1/CABIN1/ASF1a) complex that deposits the variant histone H3.3 on chromatin independently of replication. Lack of HIRA has general effects on chromatin and gene expression dynamics in embryonic stem cells and mouse oocytes. Here we describe the conditional ablation of Hira in the cardiogenic mesoderm of mice. We observed surface oedema, ventricular and atrial septal defects and embryonic lethality. We identified dysregulation of a subset of cardiac genes, notably upregulation of troponins Tnni2 and Tnnt3, involved in cardiac contractility and decreased expression of Epha3, a gene necessary for the fusion of the muscular ventricular septum and the atrioventricular cushions. We found that HIRA binds GAGA rich DNA loci in the embryonic heart, and in particular a previously described enhancer of Tnni2/Tnnt3 (TTe) bound by the transcription factor NKX2.5. HIRA-dependent H3.3 enrichment was observed at the TTe in embryonic stem cells (ESC) differentiated toward cardiomyocytes in vitro. Thus, we show here that HIRA has locus-specific effects on gene expression and that histone chaperone activity is vital for normal heart development, impinging on pathways regulated by an established cardiac transcription factor.

Indexed as

Gene Expression RegulationAnimalsCell Cycle ProteinsCell DifferentiationCell LineageCells, CulturedEmbryo, MammalianEmbryonic Stem CellsHeartHistone ChaperonesHomeobox Protein Nkx-2.5MiceMice, KnockoutMyocytes, CardiacTranscription FactorsTroponinCell Cycle ProteinsHira protein, mouseHistone ChaperonesHomeobox Protein Nkx-2.5Nkx2-5 protein, mouseTranscription FactorsTroponinTroponin Itroponin T3, skeletal, fast, mouse

Identifiers

PMID27518902
PMCPMC4982693
OpenAlexW2507601502

What OpenQuestion holds

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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.