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Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks

Author

Listed:
  • Mun-Kit Choy

    (The University of Manchester)

  • Biola M. Javierre

    (The Babraham Institute
    Campus ICO-Germans Trias I Pujol)

  • Simon G. Williams

    (The University of Manchester)

  • Stephanie L. Baross

    (The University of Manchester)

  • Yingjuan Liu

    (The University of Manchester)

  • Steven W. Wingett

    (The Babraham Institute)

  • Artur Akbarov

    (The University of Manchester)

  • Chris Wallace

    (University of Cambridge
    University of Cambridge)

  • Paula Freire-Pritchett

    (The Babraham Institute
    Medical Research Council Laboratory of Molecular Biology)

  • Peter J. Rugg-Gunn

    (The Babraham Institute)

  • Mikhail Spivakov

    (The Babraham Institute)

  • Peter Fraser

    (The Babraham Institute
    Florida State University)

  • Bernard D. Keavney

    (The University of Manchester)

Abstract

Long-range chromosomal interactions bring distal regulatory elements and promoters together to regulate gene expression in biological processes. By performing promoter capture Hi-C (PCHi-C) on human embryonic stem cell-derived cardiomyocytes (hESC-CMs), we show that such promoter interactions are a key mechanism by which enhancers contact their target genes after hESC-CM differentiation from hESCs. We also show that the promoter interactome of hESC-CMs is associated with expression quantitative trait loci (eQTLs) in cardiac left ventricular tissue; captures the dynamic process of genome reorganisation after hESC-CM differentiation; overlaps genome-wide association study (GWAS) regions associated with heart rate; and identifies new candidate genes in such regions. These findings indicate that regulatory elements in hESC-CMs identified by our approach control gene expression involved in ventricular conduction and rhythm of the heart. The study of promoter interactions in other hESC-derived cell types may be of utility in functional investigation of GWAS-associated regions.

Suggested Citation

  • Mun-Kit Choy & Biola M. Javierre & Simon G. Williams & Stephanie L. Baross & Yingjuan Liu & Steven W. Wingett & Artur Akbarov & Chris Wallace & Paula Freire-Pritchett & Peter J. Rugg-Gunn & Mikhail Sp, 2018. "Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04931-0
    DOI: 10.1038/s41467-018-04931-0
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    Cited by:

    1. Laureano Tomás-Daza & Llorenç Rovirosa & Paula López-Martí & Andrea Nieto-Aliseda & François Serra & Ainoa Planas-Riverola & Oscar Molina & Rebecca McDonald & Cedric Ghevaert & Esther Cuatrecasas & Do, 2023. "Low input capture Hi-C (liCHi-C) identifies promoter-enhancer interactions at high-resolution," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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