Evidence map›Paper›PMID 36263775›Full record

ArticleCirculation research2022

GATA4 Regulates Developing Endocardium Through Interaction With ETS1.

Pingzhu Zhou, Yan Zhang, Isha Sethi, Lincai Ye, Michael A Trembley, Yangpo Cao, Brynn N Akerberg, Feng Xiao, Xiaoran Zhang, Kai Li and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2022. 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
2.3field-weighted citation impact, top 11% 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, 27 citations in OpenAlex.

  1. Article
  2. ETS‑1/ETS‑2 transcription factors in CVD (Review).International journal of molecular medicine · 2026
    Review
  3. Article
  4. Article
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  8. Discovery ofDiagnostics (Basel, Switzerland) · 2025
    Article
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  12. Review
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  18. Review
  19. Regulation and Function of FOXC1 in Osteoblasts.Journal of developmental biology · 2023
    Article
  20. [High expression of Circ-PALLD in heart failure is transcriptionally regulated by the transcription factor GATA4].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023
    Article
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

16 authors at 4 institutions in 2 countries.

Pingzhu ZhouDepartment of Cardiology, Boston Children's Hospital, MA (P.Z., Y.Z., I.S., M.A.T., Y.C., B.N.A., F.X., X.Z., K.L., B.D.L., N.M., Q.M., W.T.P.).
Yan ZhangDepartment of Cardiology, Boston Children's Hospital, MA (P.Z., Y.Z., I.S., M.A.T., Y.C., B.N.A., F.X., X.Z., K.L., B.D.L., N.M., Q.M., W.T.P.).
Isha SethiDepartment of Cardiology, Boston Children's Hospital, MA (P.Z., Y.Z., I.S., M.A.T., Y.C., B.N.A., F.X., X.Z., K.L., B.D.L., N.M., Q.M., W.T.P.).
Lincai YeDepartment of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, China (L.Y.).ORCID 0000-0001-8808-2810
Michael A TrembleyDepartment of Cardiology, Boston Children's Hospital, MA (P.Z., Y.Z., I.S., M.A.T., Y.C., B.N.A., F.X., X.Z., K.L., B.D.L., N.M., Q.M., W.T.P.).
Yangpo CaoDepartment of Cardiology, Boston Children's Hospital, MA (P.Z., Y.Z., I.S., M.A.T., Y.C., B.N.A., F.X., X.Z., K.L., B.D.L., N.M., Q.M., W.T.P.).ORCID 0000-0001-7386-8247
Brynn N AkerbergDepartment of Cardiology, Boston Children's Hospital, MA (P.Z., Y.Z., I.S., M.A.T., Y.C., B.N.A., F.X., X.Z., K.L., B.D.L., N.M., Q.M., W.T.P.).
Feng XiaoDepartment of Cardiology, Boston Children's Hospital, MA (P.Z., Y.Z., I.S., M.A.T., Y.C., B.N.A., F.X., X.Z., K.L., B.D.L., N.M., Q.M., W.T.P.).ORCID 0000-0002-9084-9328
Xiaoran ZhangDepartment of Cardiology, Boston Children's Hospital, MA (P.Z., Y.Z., I.S., M.A.T., Y.C., B.N.A., F.X., X.Z., K.L., B.D.L., N.M., Q.M., W.T.P.).ORCID 0000-0003-0979-7100
Kai LiDepartment of Cardiology, Boston Children's Hospital, MA (P.Z., Y.Z., I.S., M.A.T., Y.C., B.N.A., F.X., X.Z., K.L., B.D.L., N.M., Q.M., W.T.P.).
Blake D JardinDepartment of Cardiology, Boston Children's Hospital, MA (P.Z., Y.Z., I.S., M.A.T., Y.C., B.N.A., F.X., X.Z., K.L., B.D.L., N.M., Q.M., W.T.P.).
Neil MazumdarDepartment of Cardiology, Boston Children's Hospital, MA (P.Z., Y.Z., I.S., M.A.T., Y.C., B.N.A., F.X., X.Z., K.L., B.D.L., N.M., Q.M., W.T.P.).
Qing MaDepartment of Cardiology, Boston Children's Hospital, MA (P.Z., Y.Z., I.S., M.A.T., Y.C., B.N.A., F.X., X.Z., K.L., B.D.L., N.M., Q.M., W.T.P.).ORCID 0000-0002-5625-1330
Aibin HeState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China (A.H.).ORCID 0000-0002-3489-2305
Bin ZhouState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, China (B.Z.).ORCID 0000-0001-5278-5522
William T PuDepartment of Cardiology, Boston Children's Hospital, MA (P.Z., Y.Z., I.S., M.A.T., Y.C., B.N.A., F.X., X.Z., K.L., B.D.L., N.M., Q.M., W.T.P.).ORCID 0000-0002-4551-8079
Boston Children's Hospital · USCenter for Excellence in Molecular Cell Science · CNPeking University · CNShanghai Children's Medical Center · CN

Funding

Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4M
Regulation of Cardiac Development in Health and DiseaseUM1HL098166 · NHLBI · HARVARD MEDICAL SCHOOL · PI PENNACCHIO, LEN ALEXANDER, PU, WILLIAM TSWENCHING · 2015 to 2019
$4.4M
Regulation of Cardiomyocyte MaturationR01HL146634 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI PU, WILLIAM TSWENCHING · 2019 to 2022
$2.4M
Transcriptional regulation of arteriovenous differentiationR01HL138571 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI PU, WILLIAM TSWENCHING · 2017 to 2020
$2.2M
NHLBI NIH HHS R01 HL138571NHLBI NIH HHS R01 HL146634NHLBI NIH HHS UM1 HL098166NICHD NIH HHS P50 HD105351
6 · The paper itself

Abstract

backgroundThe pioneer transcription factor (TF) GATA4 (GATA Binding Protein 4) is expressed in multiple cardiovascular lineages and is essential for heart development. GATA4 lineage-specific occupancy in the developing heart underlies its lineage specific activities. Here, we characterized GATA4 chromatin occupancy in cardiomyocyte and endocardial lineages, dissected mechanisms that control lineage specific occupancy, and analyzed GATA4 regulation of endocardial gene expression.

methodsWe mapped GATA4 chromatin occupancy in cardiomyocyte and endocardial cells of embryonic day 12.5 (E12.5) mouse heart using lineage specific, Cre-activated biotinylation of GATA4. Regulation of GATA4 pioneering activity was studied in cell lines stably overexpressing GATA4. GATA4 regulation of endocardial gene expression was analyzed using single cell RNA sequencing and luciferase reporter assays.

resultsCardiomyocyte-selective and endothelial-selective GATA4 occupied genomic regions had features of lineage specific enhancers. Footprints within cardiomyocyte- and endothelial-selective GATA4 regions were enriched for NKX2-5 (NK2 homeobox 5) and ETS1 (ETS Proto-Oncogene 1) motifs, respectively, and both of these TFs interacted with GATA4 in co-immunoprecipitation assays. In stable NIH3T3 cell lines expressing GATA4 with or without NKX2-5 or ETS1, the partner TFs re-directed GATA4 pioneer binding and augmented its ability to open previously inaccessible regions, with ETS1 displaying greater potency as a pioneer partner than NKX2-5. Single-cell RNA sequencing of embryonic hearts with endothelial cell-specific

conclusionsLineage selective non-pioneer TFs NKX2-5 and ETS1 guide the activity of pioneer TF GATA4 to bind and open chromatin and create active enhancers and mechanistically link ETS1 interaction to GATA4 regulation of endocardial development.

Indexed as

EndocardiumGATA4 Transcription FactorProto-Oncogene Protein c-ets-1AnimalsChromatinMiceMyocytes, CardiacNIH 3T3 CellsChromatinEts1 protein, mouseGata4 protein, mouseGATA4 Transcription FactorProto-Oncogene Protein c-ets-1animalschromatingene expressiongenomicsimmunoprecipitation

Identifiers

PMID36263775
PMCPMC9669226
OpenAlexW4306867460

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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.