Genome-wide landscape and functional necessity of heart enhancers

Analysis of the transcriptional changes in the heart resulting from the loss of cardiac enhancers. As there remains a limited understanding of the phenotypic consequences of enhancer mutations, we examined the impact of loss of function mutations by deleting two enhancers near heart disease genes in mice. In both cases, we observed loss of target gene expression, as well as cardiac phenotypes consistent with heart disease in humans, highlighting the functional importance of enhancers for normal heart function, as well as the potential contribution of enhancer mutations to heart disease. Overall design: Hearts were dissected from wild-type and enhancer-null mice (either embryonic or adult) and processed for deep RNA-seq analysis.

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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