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GATA4 Regulates Developing Endocardium Through Interaction With ETS1.

Pingzhu Zhou1, Yan Zhang1, Isha Sethi1

  • 1Department 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.).

Circulation Research
|October 20, 2022
PubMed
Summary
This summary is machine-generated.

Pioneer transcription factor GATA4 (GATA Binding Protein 4) binding is guided by NKX2-5 and ETS1 in heart development. ETS1 interaction with GATA4 is key for regulating endocardial gene expression during heart development.

Keywords:
animalschromatingene expressiongenomicsimmunoprecipitation

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Area of Science:

  • Cardiovascular Biology
  • Developmental Biology
  • Epigenetics

Background:

  • GATA4 (GATA Binding Protein 4) is a crucial transcription factor for heart development, with lineage-specific roles.
  • Understanding GATA4's occupancy and regulatory mechanisms in different heart cell types is essential.

Purpose of the Study:

  • To characterize GATA4 chromatin occupancy in cardiomyocyte and endocardial lineages.
  • To dissect mechanisms controlling lineage-specific GATA4 binding.
  • To analyze GATA4's regulation of endocardial gene expression.

Main Methods:

  • Mapped GATA4 chromatin occupancy using lineage-specific biotinylation in embryonic mouse hearts.
  • Studied GATA4 pioneering activity regulation in cell lines.
  • Analyzed GATA4's role in endocardial gene expression via single-cell RNA sequencing and reporter assays.

Main Results:

  • GATA4 occupied regions in cardiomyocytes and endocardial cells acted as lineage-specific enhancers.
  • NKX2-5 and ETS1 motifs were enriched in these regions, and both interacted with GATA4.
  • ETS1 more potently redirected GATA4 binding and chromatin opening than NKX2-5, linking ETS1 to endocardial development.

Conclusions:

  • Lineage-specific transcription factors NKX2-5 and ETS1 guide pioneer transcription factor GATA4 binding.
  • These interactions open chromatin and create active enhancers.
  • ETS1 interaction with GATA4 mechanistically links to endocardial development.