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Genome-wide compendium and functional assessment of in vivo heart enhancers

Dickel, Diane E., Barozzi, Iros, Zhu, Yiwen, Fukuda-Yuzawa, Yoko, Osterwalder, Marco, Mannion, Brandon J., May, Dalit, Spurrell, Cailyn H., Plajzer-Frick, Ingrid, Pickle, Catherine S., Lee, Elizabeth, Garvin, Tyler H., Kato, Momoe, Akiyama, Jennifer A., Afzal, Veena, Lee, Ah Young, Gorkin, David U., Ren, Bing, Rubin, Edward M., Visel, Axel, Pennacchio, Len A.·2016·Nature Communications
DOI 10.1038/ncomms12923PMC PMC5059478
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Abstract

Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of >35 epigenomic data sets from mouse and human pre- and postnatal hearts we created a comprehensive reference of >80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs of two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function.

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Metadata

Authors
Dickel, D. E., Barozzi, I., Zhu, Y., Fukuda-Yuzawa, Y., Osterwalder, M., Mannion, B. J., May, D., Spurrell, C. H., Plajzer-Frick, I., Pickle, C. S., Lee, E., Garvin, T. H., Kato, M., Akiyama, J. A., Afzal, V., Lee, A. Y., Gorkin, D. U., Ren, B., Rubin, E. M., Visel, A., & Pennacchio, L. A.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2016-10-05
Volume
7
Issue
1
ISSN
2041-1723
DOI
10.1038/ncomms12923
PMC
PMC5059478
Cited by
93
References
13
Language
en
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