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BRG1-SWI/SNF-dependent regulation of the Wt1 transcriptional landscape mediates epicardial activity during heart development and disease

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Listed:
  • Joaquim Miguel Vieira

    (Burdon Sanderson Cardiac Science Centre, Anatomy and Genetics, University of Oxford
    Molecular Medicine Unit, UCL Institute of Child Health)

  • Sara Howard

    (Molecular Medicine Unit, UCL Institute of Child Health)

  • Cristina Villa del Campo

    (Burdon Sanderson Cardiac Science Centre, Anatomy and Genetics, University of Oxford)

  • Sveva Bollini

    (Burdon Sanderson Cardiac Science Centre, Anatomy and Genetics, University of Oxford
    Present address: Department of Experimental Medicine, University of Genova, L.go R. Benzi 10, Genova 16033, Italy)

  • Karina N. Dubé

    (Molecular Medicine Unit, UCL Institute of Child Health)

  • Megan Masters

    (Burdon Sanderson Cardiac Science Centre, Anatomy and Genetics, University of Oxford)

  • Damien N. Barnette

    (Burdon Sanderson Cardiac Science Centre, Anatomy and Genetics, University of Oxford)

  • Mala Rohling

    (Burdon Sanderson Cardiac Science Centre, Anatomy and Genetics, University of Oxford)

  • Xin Sun

    (Burdon Sanderson Cardiac Science Centre, Anatomy and Genetics, University of Oxford)

  • Laura E. Hankins

    (Burdon Sanderson Cardiac Science Centre, Anatomy and Genetics, University of Oxford)

  • Daria Gavriouchkina

    (Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford)

  • Ruth Williams

    (Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford)

  • Daniel Metzger

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U964/CNRS UMR 7104/Université de Strasbourg)

  • Pierre Chambon

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U964/CNRS UMR 7104/Université de Strasbourg)

  • Tatjana Sauka-Spengler

    (Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford)

  • Benjamin Davies

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Paul R. Riley

    (Burdon Sanderson Cardiac Science Centre, Anatomy and Genetics, University of Oxford
    Molecular Medicine Unit, UCL Institute of Child Health)

Abstract

Epicardium-derived cells (EPDCs) contribute cardiovascular cell types during development and in adulthood respond to Thymosin β4 (Tβ4) and myocardial infarction (MI) by reactivating a fetal gene programme to promote neovascularization and cardiomyogenesis. The mechanism for epicardial gene (re-)activation remains elusive. Here we reveal that BRG1, the essential ATPase subunit of the SWI/SNF chromatin–remodelling complex, is required for expression of Wilms’ tumour 1 (Wt1), fetal EPDC activation and subsequent differentiation into coronary smooth muscle, and restores Wt1 activity upon MI. BRG1 physically interacts with Tβ4 and is recruited by CCAAT/enhancer-binding protein β (C/EBPβ) to discrete regulatory elements in the Wt1 locus. BRG1-Tβ4 co-operative binding promotes optimal transcription of Wt1 as the master regulator of embryonic EPDCs. Moreover, chromatin immunoprecipitation-sequencing reveals BRG1 binding at further key loci suggesting SWI/SNF activity across the fetal epicardial gene programme. These findings reveal essential functions for chromatin–remodelling in the activation of EPDCs during cardiovascular development and repair.

Suggested Citation

  • Joaquim Miguel Vieira & Sara Howard & Cristina Villa del Campo & Sveva Bollini & Karina N. Dubé & Megan Masters & Damien N. Barnette & Mala Rohling & Xin Sun & Laura E. Hankins & Daria Gavriouchkina &, 2017. "BRG1-SWI/SNF-dependent regulation of the Wt1 transcriptional landscape mediates epicardial activity during heart development and disease," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms16034
    DOI: 10.1038/ncomms16034
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    Cited by:

    1. Cornelis J. Boogerd & Ilaria Perini & Eirini Kyriakopoulou & Su Ji Han & Phit La & Britt Swaan & Jari B. Berkhout & Danielle Versteeg & Jantine Monshouwer-Kloots & Eva Rooij, 2023. "Cardiomyocyte proliferation is suppressed by ARID1A-mediated YAP inhibition during cardiac maturation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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