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Publication
Genome-wide compendium and functional assessment of in vivo heart enhancers.
Authors Dickel DE, Barozzi I, Zhu Y, Fukuda-Yuzawa Y, Osterwalder M, Mannion BJ, May D,
Spurrell CH, Plajzer-Frick I, Pickle CS, Lee E, Garvin TH, Kato M, Akiyama JA,
Afzal V, Lee AY, Gorkin DU, Ren B, Rubin EM, Visel A, Pennacchio LA
Submitted By Submitted Externally on 12/6/2016
Status Published
Journal Nature communications
Year 2016
Date Published 10/1/2016
Volume : Pages 7 : 12923
PubMed Reference 27703156
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.




Strains
StrainDevelopment StatusCreation MethodOptions
B6;129S6-Rr34tm1.1LapPhenotyping ongoingknockout
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B6;129S6-Rr35tm1.1LapPhenotyping ongoingknockout
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