Determining the 3D genome structure of a single mammalian cell with Dip-C

3D genome structure is highly heterogeneous among single cells and contributes to cellular functions. Our single-cell chromatin conformation capture (3C/Hi-C) technique, Dip-C, enables high-resolution (20 kb or ∼100 nm) 3D genome structure determination from single human and mouse cells. Dip-C is robust, fast, cheap, and does not require specialized equipment. This protocol describes using human and mouse brain samples to perform Dip-C, which has also been applied to other tissue types including the human blood and mouse eye, nose, and embryo. For complete details on the use and execution of this protocol, please refer to Tan et al. (2021).