Architectural proteins for the formation and maintenance of the 3D genome.

Eukaryotic genomes are densely packaged into hierarchical three-dimensional (3D) structures that contain information about gene regulation and many other biological processes. With the development of imaging and sequencing-based technologies, 3D genome studies have revealed that the high-order chromatin structure is composed of hierarchical levels, including chromosome territories, A/B compartments, topologically associated domains, and chromatin loops. However, how this chromatin architecture is formed and maintained is not completely clear. In this review, we introduce experimental methods to investigate the 3D genome, review major architectural proteins that regulate 3D chromatin organization in mammalian cells, such as CTCF (CCCTC-binding factor), cohesin, lamins, and transcription factors, and discuss relevant mechanisms such as phase separation.