HiChIP: Efficient and sensitive analysis of protein-directed genome architecture

Three-dimensional genome structure is central to gene control, but current technologies are often impractical for many biological questions due to cell and read number requirements. Here we present HiChIP, a protein-centric chromatin conformation method. HiChIP improves the fraction of conformation-informative reads by over 10-fold and lowers input requirement greater than 100-fold to 1 million cells. HiChIP of cohesin reveals multi-scale genome architecture with greater signal to noise than in situ Hi-C. Thus, HiChIP will enable insight into the genome’s three-dimensional structure and regulation in once-inaccessible biological systems. [HiChIP cohesin] GM and mESC 25m (25 million cell input): 2 biological with 2 technical replicates, mESC 10m, 5m, and 1m: 2 technical replicates [HiChIP oct4] mESC 25m (25 million cell input): 2 biological with 2 technical replicates