Evidence map›Paper›PMID 25149110›Full record

ArticleJournal of molecular and cellular cardiology2014

Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease.

Samir Ounzain, Iole Pezzuto, Rudi Micheletti, Frédéric Burdet, Razan Sheta, Mohamed Nemir, Christine Gonzales, Alexandre Sarre, Michael Alexanian, Matthew J Blow and 5 more

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

Article in Journal of molecular and cellular cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
6.3field-weighted citation impact, top 2% 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

71 citing papers in PubMed, 139 citations in OpenAlex.

  1. Review
  2. Review
  3. Role of eRNAs in Cardiovascular Diseases.Current cardiology reviews · 2026
    Review
  4. Review
  5. Article
  6. Posttranscriptional Regulation by Proteins and Noncoding RNAs.Advances in experimental medicine and biology · 2024
    Article
  7. The Role of Long Non-Coding RNAs in Cardiovascular Diseases.International journal of molecular sciences · 2023
    Review
  8. Article
  9. Article
  10. Enhancer RNA (eRNA) in Human Diseases.International journal of molecular sciences · 2022
    Review
  11. Article
  12. Article
  13. Fish-Ing for Enhancers in the Heart.International journal of molecular sciences · 2021
    Review
  14. Review
  15. Long Noncoding RNAs in Cardiac Development.Cold Spring Harbor perspectives in biology · 2020
    Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Article

11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 3 countries.

Samir OunzainExperimental Cardiology Unit, Department of Medicine, University of Lausanne Medical School, Lausanne, Switzerland. Electronic address: samir.ounzain@chuv.ch.
Iole PezzutoExperimental Cardiology Unit, Department of Medicine, University of Lausanne Medical School, Lausanne, Switzerland.
Rudi MichelettiExperimental Cardiology Unit, Department of Medicine, University of Lausanne Medical School, Lausanne, Switzerland.
Frédéric BurdetVitalIT, Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland.
Razan ShetaExperimental Cardiology Unit, Department of Medicine, University of Lausanne Medical School, Lausanne, Switzerland.
Mohamed NemirExperimental Cardiology Unit, Department of Medicine, University of Lausanne Medical School, Lausanne, Switzerland.
Christine GonzalesExperimental Cardiology Unit, Department of Medicine, University of Lausanne Medical School, Lausanne, Switzerland.
Alexandre SarreCardiovascular Assessment Facility, University of Lausanne, Lausanne, Switzerland.
Michael AlexanianExperimental Cardiology Unit, Department of Medicine, University of Lausanne Medical School, Lausanne, Switzerland.
Matthew J BlowGenomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; US Department of Energy Joint Genome Institute, Walnut Creek, CA, USA.
Dalit MayGenomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; US Department of Energy Joint Genome Institute, Walnut Creek, CA, USA.
Rory JohnsonBioinformatics and Genomics Group, Centre for Genomic Regulation, Barcelona, Spain.
Jérôme DauvillierVitalIT, Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland.
Len A PennacchioGenomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; US Department of Energy Joint Genome Institute, Walnut Creek, CA, USA.
Thierry PedrazziniExperimental Cardiology Unit, Department of Medicine, University of Lausanne Medical School, Lausanne, Switzerland. Electronic address: thierry.pedrazzini@chuv.ch.
University of Lausanne · CHJoint Genome Institute · USCentre for Genomic Regulation · ESSIB Swiss Institute of Bioinformatics · CH

Funding

Generation of an In Vivo Human Genome Transcriptional Enhancer DatasetR01HG003988 · NHGRI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Len Alexander Pennacchio · 2006 to 2026
$24.1M
NHGRI NIH HHS R01 HG003988NHGRI NIH HHS R01HG003988
6 · The paper itself

Abstract

The key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Through a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.

Indexed as

Enhancer Elements, GeneticAnimalsCells, CulturedEmbryonic Stem CellsGene ExpressionGene Expression Regulation, DevelopmentalHeartHeart DiseasesHumansMiceMuscle ProteinsPrimary Cell CultureRNA, Long NoncodingMuscle ProteinsRNA, Long NoncodingCardiac developmentEnhancersGene regulationGene regulatory networksHeart failureLong noncoding RNA (lncRNAs)

Identifiers

PMID25149110
PMCPMC4445080
OpenAlexW2096223470

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.