GSE126571
Genome-wide fetalization of enhancer architecture in heart disease [ChIP-Seq]
Heart disease is associated with re-expression of key transcription factors normally active only during prenatal development of the heart.  However, the impact of this reactivation on the genome-wide regulatory landscape in heart disease has remained obscure.  Here we show that pervasive epigenomic changes occur in heart disease, with thousands of regulatory sequences reacquiring fetal-like chromatin signatures.  We used RNA-seq and ChIP-seq targeting a histone modification associated with active transcriptional enhancers to generate genome-wide enhancer maps from left ventricle tissue from 18 healthy controls and 18 individuals with idiopathic dilated cardiomyopathy (DCM).  Healthy individuals had a highly reproducible epigenomic landscape, consisting of more than 31,000 predicted heart enhancers.  In contrast, we observed reproducible disease-associated gains or losses of activity at more than 7,500 predicted heart enhancers.  Next, we profiled human fetal heart tissue by ChIP-seq and RNA-seq.  Comparison with adult tissues revealed that the heart disease epigenome and transcriptome both shift toward a fetal-like state, with more than 3,400 individual enhancers sharing fetal regulatory properties.  Our results demonstrate widespread epigenomic changes in DCM, and we provide a comprehensive data resource (http://heart.lbl.gov) for the mechanistic exploration of heart disease etiology. Overall design: H3K27ac ChIP-seq of adult left ventricle tissue from healthy hearts, adult explanted hearts with ideopathic dilated cardiomyopathy, and embryonic/fetal hearts