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

Mun-Kit Choy; Biola M Javierre; Simon Williams; Stephanie Baross; Yingjuan Liu; Steven W. Wingett; Artur Akbarov; Chris Wallace; Paula Freire-Pritchett; Peter J. Rugg-Gunn; Mikhail Spivakov; Peter Fraser; Bernard Keavney

doi:10.1038/s41467-018-04931-0

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

Mun-Kit Choy, Biola M Javierre, Simon Williams, Stephanie Baross, Yingjuan Liu, Steven W. Wingett, Artur Akbarov, Chris Wallace, Paula Freire-Pritchett, Peter J. Rugg-Gunn, Mikhail Spivakov, Peter Fraser, Bernard Keavney

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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.

Original language	English
Journal	Nature Communications
Early online date	28 Jun 2018
DOIs	https://doi.org/10.1038/s41467-018-04931-0
Publication status	Published - 28 Jun 2018

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Choy, M.-K., Javierre, B. M., Williams, S., Baross, S., Liu, Y., Wingett, S. W., Akbarov, A., Wallace, C., Freire-Pritchett, P., Rugg-Gunn, P. J., Spivakov, M., Fraser, P., & Keavney, B. (2018). Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks. Nature Communications. https://doi.org/10.1038/s41467-018-04931-0

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

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.",

author = "Mun-Kit Choy and Javierre, {Biola M} and Simon Williams and Stephanie Baross and Yingjuan Liu and Wingett, {Steven W.} and Artur Akbarov and Chris Wallace and Paula Freire-Pritchett and Rugg-Gunn, {Peter J.} and Mikhail Spivakov and Peter Fraser and Bernard Keavney",

year = "2018",

month = jun,

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doi = "10.1038/s41467-018-04931-0",

language = "English",

journal = "Nature Communications",

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TY - JOUR

T1 - Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks

AU - Choy, Mun-Kit

AU - Javierre, Biola M

AU - Williams, Simon

AU - Baross, Stephanie

AU - Liu, Yingjuan

AU - Wingett, Steven W.

AU - Akbarov, Artur

AU - Wallace, Chris

AU - Freire-Pritchett, Paula

AU - Rugg-Gunn, Peter J.

AU - Spivakov, Mikhail

AU - Fraser, Peter

AU - Keavney, Bernard

PY - 2018/6/28

Y1 - 2018/6/28

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-018-04931-0

DO - 10.1038/s41467-018-04931-0

M3 - Article

SN - 2041-1723

JO - Nature Communications

JF - Nature Communications

ER -

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

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