Integrative epigenomic profiling reveal AP-1 is a key regulator in intrahepatich cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor with poor prognosis while its mechanisms of pathogenesis remain elusive. In this study, we performed systemic epigenomic and transcriptomic profiling via MNase-seq, ChIP-seq and RNA-seq in normal cholangiocyte and ICC cell lines. We showed that active histone modifications (H3K4me3, H3K4me1 and H3K27ac) were less enriched on cancer-related genes in ICC cell lines compared to control. The region of different histone modification patterns is enrichment in sites of AP-1 motif. Subsequent analysis showed that ICC had different nucleosome occupancy in differentially expressed genes compared to a normal cell line. Furthermore, we found that AP-1 plays a key role in ICC and regulates ICC-related genes through its AP-1 binding site. This study is the first report showing the global features of histone modification, transcript, and nucleosome profiles in ICC; we also show that the transcription factor AP-1 might be a key target gene in ICC.