High-throughput Pore-C reveals the single-allele topology and cell type-specificity of 3D genome folding

作者：Jiayong Zhong, Longjian Niu, Zhuobin Lin, Xin Bai, Ying Chen, Feng Luo, Chunhui Hou, Chuan‐Le Xiao · 发表于：Nature Communications · 年份：2023 · DOI：10.1038/s41467-023-36899-x · 被引用次数：52 · 研究领域：Genomics and Chromatin Dynamics、Chromosomal and Genetic Variations、Genomics and Phylogenetic Studies

Canonical three-dimensional (3D) genome structures represent the ensemble average of pairwise chromatin interactions but not the single-allele topologies in populations of cells. Recently developed Pore-C can capture multiway chromatin contacts that reflect regional topologies of single chromosomes. By carrying out high-throughput Pore-C, we reveal extensive but regionally restricted clusters of single-allele topologies that aggregate into canonical 3D genome structures in two human cell types. We show that fragments in multi-contact reads generally coexist in the same TAD. In contrast, a concurrent significant proportion of multi-contact reads span multiple compartments of the same chromatin type over megabase distances. Synergistic chromatin looping between multiple sites in multi-contact reads is rare compared to pairwise interactions. Interestingly, the single-allele topology clusters are cell type-specific even inside highly conserved TADs in different types of cells. In summary, HiPore-C enables global characterization of single-allele topologies at an unprecedented depth to reveal elusive genome folding principles.