High-throughput methods based on chromosome conformation capture have greatly advanced our understanding of the three-dimensional (3D) organization of genomes but are limited in resolution by their reliance on restriction enzymes. Here we describe a method called DNase Hi-C for comprehensively mapping global chromatin contacts. DNase Hi-C uses DNase I for chromatin fragmentation, leading to greatly improved efficiency and resolution over that of 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 large intergenic noncoding RNA (lincRNA) promoters in two human cell lines. Our results revealed 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 the cell type–specific 3D organization of lincRNA genes.
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We thank S. Fields and M. Groudine for critical reading of the manuscript. This work was supported by US National Institutes of Health grants R01 GM098039 (C.A.B.), GM046883 (C.M.D.) and R01 U41HG007000 (W.S.N.).
The authors declare no competing financial interests.
Supplementary Figures 1–17, Supplementary Tables 1–4, 6, 7, 11–15 and 24 and Supplementary Notes 1–6 (PDF 38883 kb)
The 220kb P-E library (XLS 59 kb)
List of contact partners identified by targeted DNase Hi-C P-E in H1 cells (XLSX 153 kb)
List of contact partners identified by targeted DNase Hi-C P-E in K562 cells (XLSX 175 kb)
The lincRNA P library (XLSX 182 kb)
List of contact partners identified by targeted DNase Hi-C incRNA in H1 cells (XLSX 1027 kb)
List of contact partners identified by targeted DNase Hi-C lincRNA in K562 cells (XLSX 781 kb)
Summary of enrichment analysis of Segway cis-elements (XLSX 18 kb)
Summary of enrichment analysis of DNase hypersensitive sites(DHSs) (XLSX 9 kb)
Summary of enrichment analysis of FAIRE-seq peaks (XLSX 9 kb)
Summary of enrichment analysis of super-enhancers (XLSX 174 kb)
Summary of enrichment analysis of TFBSs (XLSX 23 kb)
Adaptor and primer sequences (XLSX 12 kb)
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Ma, W., Ay, F., Lee, C. et al. Fine-scale chromatin interaction maps reveal the cis-regulatory landscape of human lincRNA genes. Nat Methods 12, 71–78 (2015). https://doi.org/10.1038/nmeth.3205
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