Enhancer connectome in primary human cells reveals target genes of disease-associated DNA elements
作者： Maxwell R. Mumbach , Ansuman T. Satpathy , Evan A. Boyle , Chao Dai , Benjamin G. Gowen
DOI: 10.1101/178269
关键词: Enhancer 、 Gene 、 Genome 、 Genomics 、 Genetics 、 Biology 、 Expression quantitative trait loci 、 Enhancer RNAs 、 CRISPR interference 、 T cell
摘要: The challenge of linking intergenic mutations to target genes has limited molecular understanding diverse human diseases. Here, we show H3K27ac HiChIP generates high-resolution contact maps active enhancers and in rare primary T cell subtypes coronary artery smooth muscle cells. Differentiation naive cells either helper 17 or regulatory create subtype-specific enhancer-promoter interactions, specifically at regions shared DNA accessibility. These data provide a principled means assigning functions autoimmune cardiovascular disease risk variants, hundreds noncoding variants putative gene targets. Target identified with are further supported by CRISPR interference activation linked enhancers, the presence expression quantitative trait loci, allele-specific enhancer loops patient-derived majority disease-associated beyond nearest linear genome, leading four-fold increase potential for
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