BL-Hi-C is an efficient and sensitive approach for capturing structural and regulatory chromatin interactions

We propose a novel in situ Hi-C method named Bridge-Linker-Hi-C (BL-Hi-C) for structural and regulatory chromatin interactions capture by restriction enzyme targeting and two-step proximity ligation. It improves the sensitivity and specificity for active chromatin loop detection and can reveal a better enhancer-promoter regulatory architecture than conventional method at a lower sequencing depth and with a simpler protocol. Overall design: BL-Hi-C was performed in K562 cell for 13 samples: 5 samples for enrichment analysis; 4 samples for enzyme digestion validation and 4 samples for proximity ligation validation.