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

Jia-Yong Zhong, Longjian Niu, Zhuo-Bin Lin, Xin Bai, Ying Chen, Feng Luo, Chunhui Hou () and Chuan-Le Xiao ()
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Jia-Yong Zhong: Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Longjian Niu: Chinese Academy of Sciences
Zhuo-Bin Lin: Sun Yat-sen University
Xin Bai: Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Ying Chen: Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Feng Luo: Clemson University
Chunhui Hou: Chinese Academy of Sciences
Chuan-Le Xiao: Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-36899-x

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