3D genome sequencing technology in its mid-teens: past, present, and future

The genome is packaged with nuclear proteins and RNAs into a complex structure known as chromatin. Its dynamic organization influences genome functions and nuclear properties. Since 2009, high-throughput DNA sequencing methods such as Hi-C and ChIA-PET have pioneered genome-wide mapping of chromatin folding architectures and have given rise to the field of three-dimensional (3D) genome biology. Now, after 15 years of development, this field has experienced a remarkable growth and is still expanding rapidly. It is significantly deepening our understanding of how genome organization affects nuclear functions in various biological systems. In this review we focus on the breakthroughs and expansion of sequencing-based technologies in mapping 3D genomic landscapes and envisage the next frontiers in advancing the 3D genome biology.