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High-throughput Pore-C reveals the Single-allele Topology and Cell Type-specificity of 3D Genome Folding
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Jia-Yong Zhong, Longjian Niu, Zhuo-Bin Lin, Xin Bai, Ying Chen, Feng Luo, Chunhui Hou, Chuan-Le Xiao |
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
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2023 |
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152453 |
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Nature Communications |
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988853/ |
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