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肝细胞癌(Hepatocellularcarcinoma,HCC)的肿瘤发生是基因组突变和表观遗传修饰变化积累的结果,但是HCC发生过程中的三维基因组构造变化仍然缺乏研究.基于此,在人源HCC细胞系PLC/PRF/5和人源正常肝细胞系L02中进行了原位Hi-C分析,并辅以转录组测序以及SMC3/CTCF/H3K27ac的染色质免疫共沉淀测序分析,借此比较两细胞系的三维基因组差异.结果显示,相较于正常肝细胞系,在PLC/PRF/5中发生了显著的染色体结构区域(Compartment)转换、三维拓扑结构域(Topologically associating domains,TAD)滑动和染色质环(Loop)的变化.以上这些染色质空间结构的差异与HCC细胞系中肿瘤特异性基因表达和启动子开放性增高具有相关性.因此,在PLC/PRF/5细胞系中的染色质三维结构差异可能在HCC肿瘤发生的表观遗传学机制中具有重要作用.“,”Genetic and epigenetic alterations accumulate in the process of hepatocellular carcinogenesis,but the role of genomic spatial organization in HCC is still unknown.Here,we performed in situ Hi-C in HCC cell line PLC/PRF/5 compared with normal liver cell line L02,together with RNA-seq and ChIP-seq of SMC3/CTCF/H3K27ac.The results indicate that there were significant compartment switching,TAD shifting and loop pattern altering in PLC/PRF/5.These spatial changes are correlated with abnormal gene expression and more opening promoter regions of the HCC cell line.Thus,the 3D genome organization alterations in PLC/PRF/5 are important in epigenetic mechanisms of HCC tumorigenesis.