GSE135953
Genome-wide chromatin state in non-failing and dilated cardiomyaphty human left ventricles [ChIP-Seq]
We conducted chromatin immunoprecipitation followed by sequencing (ChIP-seq) and proximity ligation-assisted ChIP-seq (PLAC-seq) for enhancers and promoters (E-P) using left ventricular tissues from dilated cardiomyopathy (DCM) patients and non-heart failure (NF) donors. Differential active enhancer H3K27ac and promoter H3K4me3 regions were identified between NF and DCM. While the average read density (ARD) for H3K27ac is similar between NF and DCM, the ARD of H3K4me3 is significantly lower in DCM samples than in NF.Super-enhancer (SE) analysis revealed that 929 and 129 genes linked to NF- and DCM-specific SE, respectively, and three unique SE-associated genes between NF and DCM  were identified.Moreover, the differential E-P interactions were observed in the known heart failure gene loci and are correlated with the gene expression levels. Motif analysis identified known cardiac factors and possible novel players for DCM.  We have established cistrome of four histone modifications and long-range chromatin interaction for enhancers and promoters in NF and DCM tissues. The differential histone modifications and E-P interactions were found in DCM, and these differences were associated with the gene expression level of a subset of disease-associated genes in human heart failure. Overall design: We carried out ChIPseq experiments for four histone modificatoins using the left ventricle (LV) of male patients who underwent cardiac transplantation for dilated cardiomyopathy (DCM) and in matched non-failing donors (NF)