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.

doi:10.1038/ncomms12923

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

Journal Article · Wed Oct 05 04:00:00 UTC 2016 · Nature Communications

DOI: https://doi.org/10.1038/ncomms12923 · OSTI ID:1377528

^[1]; Barozzi, Iros ^[1]; Zhu, Yiwen ^[1]; Fukuda-Yuzawa, Yoko ^[1];

^[1]; Mannion, Brandon J. ^[1]; May, Dalit ^[1]; Spurrell, Cailyn H. ^[1]; Plajzer-Frick, Ingrid ^[1]; Pickle, Catherine S. ^[1]; Lee, Elizabeth ^[1]; Garvin, Tyler H. ^[1]; Kato, Momoe ^[1]; Akiyama, Jennifer A. ^[1]; Afzal, Veena ^[1]; Lee, Ah Young ^[2]; Gorkin, David U. ^[2]; Ren, Bing ^[2]; Rubin, Edward M. ^[3];

^[4] more »

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Ludwig Institute for Cancer Research, La Jolla, CA (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Univ. of California, Berkeley, CA (United States)

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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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1377528

Journal Information:: Nature Communications, Journal Name: Nature Communications Vol. 7; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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