in situ HiPore-C reveals higher-order 3D genome folding principles

Eukaryotic genomes are folded into three-dimensional (3D) hierarchical architectures consisting of multi-way chromatin contacts that are involved in complex gene regulation. High-throughput chromosome conformation capture (Hi-C), chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) , and methods similar to these two rely on pairwise ligation of fragments in proximity in a population of cells, thus fail to reveal multi-way chromatin interactions in single allele at single fragment resolution. To explore higher-order chromatin interaction genome-widely, a straightforward strategy is integrating multi-fragment ligates preparation with third-generation sequencing technology. To achieve this purpose, we developed a protocol of in situ high throughput multi-way contact long read Pore-C sequencing (in situ HiPore-C) We performed genome-wide multi-way contact profiling analysis using data obtained from in situ HiPore-C sequencing of GM12878 and K562 cell lines. Overall design: in situ HiPore-C sequencing for GM12878 and K562 cell lines.