Revealing High-Resolution Open Chromatin-Associated Interactions by NicE-C

Chromatin interactions between cis-regulatory elements, especially enhancer-promoter interactions, are known to regulate the spatiotemporal dynamics of gene expression. Chromosome conformation capture (3C)-based methods can detect these interactions. Nicking enzyme-assisted open chromatin interaction capture (NicE-C) is a method we developed that leverages nicking enzyme-mediated open chromatin profiling with chromosome conformation capture to identify chromatin interactions specifically within open chromatin regions. This approach offers high efficiency, high resolution, low sequencing depth, and low requirements for starting material. Here, we describe a detailed step-by-step protocol for NicE-C.