Deciphering Hi-C: from 3D genome to function

Hi-C is a commonly used technology in 3D genomics which can depict global chromatin interactions across eukaryotic genome. Integrating with different datasets, it can also be applied to studying various biological questions, such as nuclear organization, gene transcription regulation, spatiotemporal development, genome assembly, and cancer genomics. During the last decade, the development and application of Hi-C have dramatically changed the view of genome architecture, chromatin conformation, and gene interaction. So far, Hi-C-related studies remain vivacious and controversial; thus, a unified standard of library construction and bioinformatics analysis are urgently needed. In this review, we have summarized its history, development, methodologies, advances, applications, shortages, and future perspectives. We discuss a few limitations of the current Hi-C technologies and future directions for improvement and highlight how Hi-C can bridge 3D structure to gene function. This review will be helpful for scientists who want to engage in the 3D genomics field; it also shows some future tracks.