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GATA-dependent regulatory switches establish atrioventricular canal specificity during heart development

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  • Sonia Stefanovic

    (Embryology and Physiology, Academic Medical Center, University of Amsterdam)

  • Phil Barnett

    (Embryology and Physiology, Academic Medical Center, University of Amsterdam)

  • Karel van Duijvenboden

    (Embryology and Physiology, Academic Medical Center, University of Amsterdam)

  • David Weber

    (Developmental Biochemistry, Biocenter and Comprehensive Heart Failure Center, University of Wuerzburg)

  • Manfred Gessler

    (Developmental Biochemistry, Biocenter and Comprehensive Heart Failure Center, University of Wuerzburg)

  • Vincent M. Christoffels

    (Embryology and Physiology, Academic Medical Center, University of Amsterdam)

Abstract

The embryonic vertebrate heart tube develops an atrioventricular canal that divides the atrial and ventricular chambers, forms atrioventricular conduction tissue and organizes valve development. Here we assess the transcriptional mechanism underlying this localized differentiation process. We show that atrioventricular canal-specific enhancers are GATA-binding site-dependent and act as switches that repress gene activity in the chambers. We find that atrioventricular canal-specific gene loci are enriched in H3K27ac, a marker of active enhancers, in atrioventricular canal tissue and depleted in H3K27ac in chamber tissue. In the atrioventricular canal, Gata4 activates the enhancers in synergy with Bmp2/Smad signalling, leading to H3K27 acetylation. In contrast, in chambers, Gata4 cooperates with pan-cardiac Hdac1 and Hdac2 and chamber-specific Hey1 and Hey2, leading to H3K27 deacetylation and repression. We conclude that atrioventricular canal-specific enhancers are platforms integrating cardiac transcription factors, broadly active histone modification enzymes and localized co-factors to drive atrioventricular canal-specific gene activity.

Suggested Citation

  • Sonia Stefanovic & Phil Barnett & Karel van Duijvenboden & David Weber & Manfred Gessler & Vincent M. Christoffels, 2014. "GATA-dependent regulatory switches establish atrioventricular canal specificity during heart development," Nature Communications, Nature, vol. 5(1), pages 1-11, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4680
    DOI: 10.1038/ncomms4680
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