Integrative Hi-C maps of pancreatic cancer

Pancreatic cancer's poor prognosis is caused by distal metastasis, which is associated with epigenomic changes. However, the roles of 3D epigenome in pancreatic cancer biology, especially its metastasis, remain unclear. Here we compare the 3D epigenomic and transcriptomic features among cells derived from pancreatic epithelial, primary and metastatic pancreatic cancer by integrated analysis of in situ Hi-C, ChIP-seq, ATAC-seq, and RNA-seq data. We found A/B compartments, topologically associated domains (TADs), chromatin loops changed significantly in metastatic pancreatic cancer cells, which is associated with epigenetic state alterations. Moreover, we identified upregulated genes, which are located in switched compartments, common TADs with epigenetic state changing, specific TAD boundaries, and metastasis-specific enhancer-promoter loops, are related to cancer metastasis. We also find that the transcription factors mediated specific enhancer-promoter loops formation are also associated with metastasis. Taken together, these results provide a 3D epigenomic map of pancreatic cancer metastasis, which expands our knowledge of the epigenetic mechanism of pancreatic cancer metastasis and enables a better understanding of pancreatic cancer pathobiology. We used in situ Hi-C to identify chromatin interactions, ChIP-seq to identify chromatin states and CTCF binding sites, ATAC-seq to evaluate chromomsome accessibility, and RNA-seq to profile transcriptomes in normal (HPNE) and pancreatic cancer cells derived from primary sites (PANC-1) and liver metastasis (Capan-1).