Large-scale discovery of enhancers from human heart tissue

Dalit May, Matthew J. Blow, Tommy Kaplan, David J. McCulley, Brian C. Jensen, Jennifer A. Akiyama, Amy Holt, Ingrid Plajzer-Frick, Malak Shoukry, Crystal Wright, Veena Afzal, Paul C. Simpson, Edward M. Rubin, Brian L. Black, James Bristow, Len A. Pennacchio*, Axel Visel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

219 Scopus citations


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 ∼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.

Original languageAmerican English
Pages (from-to)89-93
Number of pages5
JournalNature Genetics
Issue number1
StatePublished - Jan 2012

Bibliographical note

Funding Information:
The authors thank R. Hosseini and S. Phouanenavong for technical support, S. Deutsch for help in retrieving human genetic data and C. Attanasio and D. Dickel for critical comments on the manuscript. L.A.P. and A.V. were supported by a grant funded by the National Human Genome Research Institute (HG003988). B.L.B. was supported by grants from the National Heart, Lung, and Blood Institute (NHLBI, HL64658 and HL89707). D.M. and T.K. were supported by European Molecular Biology Organization (EMBO) long-term postdoctoral fellowships. B.C.J. was supported by the GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease, University of California, San Francisco (UCSF) Foundation for Cardiac Research and a grant from the NHLBI (HL096836). P.C.S. was supported by the NHLBI and the Department of Veterans Affairs. Research was performed at Lawrence Berkeley National Laboratory and at the United States Department of Energy Joint Genome Institute (Department of Energy Contract DE-AC02-05CH11231, University of California).


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