Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements.

ABSTRACT: The challenge of linking intergenic mutations to target genes has limited molecular understanding of human diseases. Here we show that H3K27ac HiChIP generates high-resolution contact maps of active enhancers and target genes in rare primary human T cell subtypes and coronary artery smooth muscle cells. Differentiation of naive T cells into T helper 17 cells or regulatory T cells creates subtype-specific enhancer-promoter interactions, specifically at regions of shared DNA accessibility. These data provide a principled means of assigning molecular functions to autoimmune and cardiovascular disease risk variants, linking hundreds of noncoding variants to putative gene targets. Target genes identified with HiChIP are further supported by CRISPR interference and activation at linked enhancers

SUBMITTER: Mumbach MR 

PROVIDER: S-EPMC5805393 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature