Pore-C: genome-wide, multi-contact, chromosome conformation capture
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The interaction frequency of genomic loci that are in close spatial proximity can be used to predict nuclear organization. Chromatin structure relies on both multi- way interactions and on DNA methylation but it has previously not been possible to view these two phenomena simultaneously. Pore-C was developed to overcome these limitations. The technique uses cross-linking to preserve the spatial orientation of the genome followed by digestion and concatemerization of multiple neighboring segments into longer, chimeric fragments. The long-read capabilities of Nanopore technology allow these fragments to be sequenced in their entirety.
With Pore-C we are able to capture both these multi-way contacts and the methylation status of genomic loci. This information can be used to reveal the genomic compartmentalization previously identified using chromatin conformation capture assays. In addition, we show that Pore-C captures multi-contact hubs and displays broad A/B compartment coherence. We utilize the multi-way nature of Pore-C chromatin concatemers to identify structural rearrangements spanning multiple chromosomes. Furthermore, we demonstrate that even when decomposed into pairwise interactions, Pore-C can be used to assist with genome scaffolding.