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

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


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

Topics: Heart, Animals, Mice, Inbred C57BL, Mice, Knockout, Humans, Mice, Histones, Echocardiography, Gene Expression Profiling, Gene Expression Regulation, Gene Expression Regulation, Developmental, Phenotype, Mutation, Genome, Human, Female, Male, Enhancer Elements, Genetic, Epigenomics, Inbred C57BL, Knockout, Developmental, Genome, Human, Enhancer Elements, Genetic, Cardiovascular, Genetics, Human Genome, Biotechnology, Heart Disease, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors
Publisher: eScholarship, University of California
Year: 2016
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