Evidence map›Paper›PMID 33040635›Full record

ArticleCirculation research2020

Genome-Wide Analysis Identifies an Essential Human TBX3 Pacemaker Enhancer.

Vincent W W van Eif, Stephanie I Protze, Fernanda M Bosada, Xuefei Yuan, Tanvi Sinha, Karel van Duijvenboden, Auriane C Ernault, Rajiv A Mohan, Vincent Wakker, Corrie de Gier-de Vries and 8 more

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

Article in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.8field-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

27 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Coronary artery disease risk gene PRDM16 regulates smooth muscle homeostasis.Journal of molecular and cellular cardiology · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Development of the Cardiac Conduction System.Advances in experimental medicine and biology · 2024
    Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 8 institutions in 7 countries.

Vincent W W van EifMedical Biology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam (V.W.W.v.E., F.M.B., K.v.D., R.A.M., V.W., C.d.G.-d.V., I.B.H., A.O.V., B.J.B., V.M.C.).
Stephanie I ProtzeMcEwen Stem Cell Institute, University Health Network and the Department of Molecular Genetics, University of Toronto (S.I.P.).
Fernanda M BosadaMedical Biology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam (V.W.W.v.E., F.M.B., K.v.D., R.A.M., V.W., C.d.G.-d.V., I.B.H., A.O.V., B.J.B., V.M.C.).
Xuefei YuanThe Hospital for Sick Children and the Department of Molecular Genetics, University of Toronto (X.Y., M.D.W., I.C.S.).
Tanvi SinhaCardiovascular Research Institute, Department of Biochemistry and Biophysics, University of California, San Francisco (T.S., B.L.B.).
Karel van DuijvenbodenMedical Biology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam (V.W.W.v.E., F.M.B., K.v.D., R.A.M., V.W., C.d.G.-d.V., I.B.H., A.O.V., B.J.B., V.M.C.).
Auriane C ErnaultExperimental Cardiology, University of Amsterdam (A.C.E., A.O.V., B.J.B.).
Rajiv A MohanMedical Biology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam (V.W.W.v.E., F.M.B., K.v.D., R.A.M., V.W., C.d.G.-d.V., I.B.H., A.O.V., B.J.B., V.M.C.).
Vincent WakkerMedical Biology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam (V.W.W.v.E., F.M.B., K.v.D., R.A.M., V.W., C.d.G.-d.V., I.B.H., A.O.V., B.J.B., V.M.C.).
Corrie de Gier-de VriesMedical Biology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam (V.W.W.v.E., F.M.B., K.v.D., R.A.M., V.W., C.d.G.-d.V., I.B.H., A.O.V., B.J.B., V.M.C.).
Ingeborg B HooijkaasMedical Biology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam (V.W.W.v.E., F.M.B., K.v.D., R.A.M., V.W., C.d.G.-d.V., I.B.H., A.O.V., B.J.B., V.M.C.).
Michael D WilsonThe Hospital for Sick Children and the Department of Molecular Genetics, University of Toronto (X.Y., M.D.W., I.C.S.).
Arie O VerkerkMedical Biology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam (V.W.W.v.E., F.M.B., K.v.D., R.A.M., V.W., C.d.G.-d.V., I.B.H., A.O.V., B.J.B., V.M.C.).
Jeroen BakkersHubrecht Institute and University Medical Center Utrecht, the Netherlands (J.B.).
Bastiaan J BoukensMedical Biology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam (V.W.W.v.E., F.M.B., K.v.D., R.A.M., V.W., C.d.G.-d.V., I.B.H., A.O.V., B.J.B., V.M.C.).
Brian L BlackCardiovascular Research Institute, Department of Biochemistry and Biophysics, University of California, San Francisco (T.S., B.L.B.).
Ian C ScottThe Hospital for Sick Children and the Department of Molecular Genetics, University of Toronto (X.Y., M.D.W., I.C.S.).
Vincent M ChristoffelsMedical Biology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam (V.W.W.v.E., F.M.B., K.v.D., R.A.M., V.W., C.d.G.-d.V., I.B.H., A.O.V., B.J.B., V.M.C.).
Amsterdam UMC Location Vrije Universiteit Amsterdam · NLUniversity of Toronto · CAInstitute of Experimental Physics of the Slovak Academy of Sciences · SKAix-Marseille Université · FRHubrecht Institute for Developmental Biology and Stem Cell Research · NLInstitute of Biophysics · BGTwitter (United States) · USUniversity Health Network · CA

Funding

Project 3: Control of cardiac transcription by MEF2 and myocardinP01HL146366 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI BLACK, BRIAN L · 2019 to 2023
$13.7M
Regulation of cardiovascular transcriptionR01HL064658 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BLACK, BRIAN L · 2000 to 2019
$5.4M
Identification and application of regulatory elements for heart regenerationR01HL136182 · NHLBI · DUKE UNIVERSITY · PI BLACK, BRIAN L, POSS, KENNETH D · 2017 to 2020
$3.1M
CIHR FRN 156318CIHR FRN86663NHLBI NIH HHS P01 HL146366NHLBI NIH HHS R01 HL064658NHLBI NIH HHS R01 HL136182
6 · The paper itself

Abstract

rationaleThe development and function of the pacemaker cardiomyocytes of the sinoatrial node (SAN), the leading pacemaker of the heart, are tightly controlled by a conserved network of transcription factors, including TBX3 (T-box transcription factor 3), ISL1 (ISL LIM homeobox 1), and SHOX2 (short stature homeobox 2). Yet, the regulatory DNA elements (REs) controlling target gene expression in the SAN pacemaker cells have remained undefined.

objectiveIdentification of the regulatory landscape of human SAN-like pacemaker cells and functional assessment of SAN-specific REs potentially involved in pacemaker cell gene regulation. METHODS AND

resultsWe performed Assay for Transposase-Accessible Chromatin using sequencing on human pluripotent stem cell-derived SAN-like pacemaker cells and ventricle-like cells and identified thousands of putative REs specific for either human cell type. We validated pacemaker cell-specific elements in the

conclusionsWe provided a genome-wide collection of candidate human pacemaker-specific REs, including the loci of

Indexed as

Biological ClocksEnhancer Elements, GeneticHeart RateAction PotentialsAnimalsCell LineEpigenesis, GeneticFemaleGene Expression Regulation, DevelopmentalGenome-Wide Association StudyHumansMaleMice, TransgenicMutationMyocytes, CardiacSinoatrial NodeT-Box Domain ProteinsTBX3 protein, humangeneticsheart ratehumanmyocyte, cardiacstem cell

Identifiers

PMID33040635
PMCPMC8153223
OpenAlexW3092641626

What Socratic holds

Textmetadata
LicenceTDM
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.