期刊
NATURE GENETICS
卷 44, 期 1, 页码 89-U125出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.1006
关键词
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资金
- National Human Genome Research Institute [HG003988]
- National Heart, Lung, and Blood Institute (NHLBI) [HL64658, HL89707, HL096836]
- European Molecular Biology Organization (EMBO)
- GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease
- University of California, San Francisco (UCSF) Foundation for Cardiac Research
- Department of Veterans Affairs
- Department of Energy [DE-AC02-05CH11231]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [K08HL096836, R01HL064658, P01HL089707] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [R01HG003988] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE019118] Funding Source: NIH RePORTER
Development and function of the human heart depend on the dynamic control of tissue-specific gene expression by distant-acting transcriptional enhancers. To generate an accurate genome-wide map of human heart enhancers, we used an epigenomic enhancer discovery approach and identified similar to 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 noncoding sequences highly enriched in human heart enhancers that is likely to facilitate downstream studies of the role of enhancers in development and pathological conditions of the heart.
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