Fine-scale chromatin interaction maps reveal the cis-regulatory landscape of human lincRNA genes

High-throughput methods based on chromosome conformation capture (3C) have greatly advanced our understanding of the three-dimensional (3D) organization of genomes but are limited in resolution by their reliance on restriction enzymes (REs). Here we describe a method called DNase Hi-C for comprehensively mapping global chromatin contacts that uses DNase I for chromatin fragmentation, leading to greatly improved efficiency and resolution compared to Hi-C. Coupling this method with DNA capture technology provides a high-throughput approach for targeted mapping of fine-scale chromatin architecture. We applied targeted DNase Hi-C to characterize the 3D organization of 998 lincRNA (long intergenic noncoding RNA) promoters in two human cell lines, thereby revealing that expression of lincRNAs is tightly controlled by complex mechanisms involving both super-enhancers and the polycomb repressive complex. Our results provide the first glimpse of a cell type-specific 3D organization of lincRNA genes.