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Development and function of the human heart depend on the dynamic control of tissue-specific gene expression by distant-acting transcriptional enhancers. While large numbers of heart enhancers have been identified using the mouse as a model system, many of these regulatory sequences are poorly conserved in the human genome. To generate an accurate genome-wide map of human heart enhancers, we used an epigenomic enhancer discovery approach and identified ~6,200 candidate enhancer sequences directly from fetal and adult human heart tissue. Consistent with their predicted function, these elements were markedly enriched near genes implicated in heart development, function and disease. To further validate their in vivo enhancer activity, we tested 65 of these human sequences in a transgenic mouse enhancer assay and observed that 43 (66%) drove reproducible reporter gene expression in the heart. These results support the discovery of a genome-wide set of non-coding sequences highly enriched in human heart enhancers which is likely to facilitate down-stream studies of the role of enhancers in development and pathological conditions of the heart. Examination of AcCBP/p300 binding in human adult heart, human fetal (16wk) heart and mouse postnatal day 2 heart

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