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

Zhong，Jia Yong1; Niu，Longjian2,3; Lin，Zhuo Bin4; Bai，Xin1; Chen，Ying1; Luo，Feng5; Hou，Chunhui2; Xiao，Chuan Le1

2023-12-01

10.1038/s41467-023-36899-x

Nature Communications   Impact Factor & Quartile

2041-1723

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.

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2-s2.0-85149936333

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1.State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-Sen University,Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science,Guangzhou,510060,China
2.State Key Laboratory of Genetic Resources and Evolution,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,650201,China
3.School of Public Health and Emergency Management,Southern University of Science and Technology,Shenzhen,518055,China
4.Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,510080,China
5.School of Computing,Clemson University,Clemson,29634-0974,United States

Zhong，Jia Yong,Niu，Longjian,Lin，Zhuo Bin,et al. High-throughput Pore-C reveals the single-allele topology and cell type-specificity of 3D genome folding[J]. Nature Communications,2023,14(1).

Zhong，Jia Yong.,Niu，Longjian.,Lin，Zhuo Bin.,Bai，Xin.,Chen，Ying.,...&Xiao，Chuan Le.(2023).High-throughput Pore-C reveals the single-allele topology and cell type-specificity of 3D genome folding.Nature Communications,14(1).

Zhong，Jia Yong,et al."High-throughput Pore-C reveals the single-allele topology and cell type-specificity of 3D genome folding".Nature Communications 14.1(2023).