A deeper knowledge of the dynamic transcriptional activity of promoters and enhancers is needed to improve mechanistic understanding of the pathogenesis of heart failure and heart diseases. In this study, we used cap analysis of gene expression (CAGE) to identify and quantify the activity of transcribed regulatory elements (TREs) in the four cardiac chambers of 21 healthy and ten failing adult human hearts. We identified 17,668 promoters and 14,920 enhancers associated with the expression of 14,519 genes. We showed how these regulatory elements are alternatively transcribed in different heart regions, in healthy versus failing hearts and in ischemic versus non-ischemic heart failure samples. Cardiac-disease-related single-nucleotide polymorphisms (SNPs) appeared to be enriched in TREs, potentially affecting the allele-specific transcription factor binding. To conclude, our open-source heart CAGE atlas will serve the cardiovascular community in improving the understanding of the role of the cardiac gene regulatory networks in cardiovascular disease and therapy.
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