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Updated: Oct 25, 2025
Deciphering High-Resolution 3D Chromatin Organization via Capture Hi-C
Published on: October 14, 2022
High-resolution Hi-C maps highlight multiscale 3D epigenome reprogramming during pancreatic cancer metastasis
Bo Ren1, Jinshou Yang1, Chengcheng Wang1
1Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100023, People's Republic of China.
Background:
Pancreatic cancer's poor prognosis is caused by distal metastasis, which is associated with epigenetic changes. However, the role of the 3D epigenome in pancreatic cancer biology, especially its metastasis, remains unclear.
Methods:
Here, we developed high-resolution 3D epigenomic maps of cells derived from normal pancreatic epithelium, primary and metastatic pancreatic cancer by in situ Hi-C, ChIP-seq, ATAC-seq, and RNA-seq to identify key genes involved in pancreatic cancer metastasis RESULTS: We found that A/B compartments, contact domains, and chromatin loops changed significantly in metastatic pancreatic cancer cells, which are associated with epigenetic state alterations. Moreover, we found that upregulated genes, which were located in switched compartments, changed contact domains, and metastasis-specific enhancer-promoter loops, were related to cancer metastasis and poor prognosis of patients with pancreatic cancer. We also found that transcription factors in specific enhancer-promoter loop formation were also associated with metastasis. Finally we demonstrated that LIPC, looped to metastasis-specific enhancers, could promote pancreatic cancer metastasis.
Conclusions:
These results highlight the multiscale 3D epigenome reprogramming during pancreatic cancer metastasis and expand our knowledge of mechanisms of gene regulation during pancreatic cancer metastasis.
