HPV-CCDC106 integration alters local chromosome architecture and hijacks an enhancer by three-dimensional genome structure remodeling in cervical cancer

• 作者: Canhui Cao Ping Hong Xingyu Huang Da Lin Gang Cao Liming Wang Bei Feng Ping Wu Hui Shen Qian Xu Ci Ren Yifan Meng Wenhua Zhi Ruidi Yu Juncheng Wei Wencheng Ding Xun Tian Qinghua Zhang Wei Li Qinglei Gao Gang Chen Kezhen Li Wing-Kin Sung Zheng Hu Hui Wang Guoliang Li Peng Wu
• 来源期刊: 遗传学报
• 年，卷（期）: 2020,（8）
• 所属期刊栏目: Original Research
• 页码范围: 435-448
• 页数: 14页
• 语种: 英文

摘要

Integration of human papillomavirus(HPV)DNA into the human genome is a reputed key driver of cervical cancer.However,the effects of HPV integration on chromatin structural organization and gene expression are largely unknown.We studied a cohort of 61 samples and identified an integration hot spot in the CCDC106 gene on chromosome 19.We then selected fresh cancer tissue that contained the unique integration loci at CCDC106 with no HPV episomal DNA and performed whole-genome,RNA,chromatin immunoprecipitation and high-throughput chromosome conformation capture(Hi-C)sequencing to identify the mechanisms of HPV integration in cervical carcinogenesis.Molecular analyses indicated that chromosome 19 exhibited significant genomic variation and differential expression densities,with cor-relation found between three-dimensional(3D)structural change and gene expression.Importantly,HPV integration divided one topologically associated domain(TAD)into two smaller TADs and hijacked an enhancer from PEG3 to CCDC106,with a decrease in PEG3 expression and an increase in CCDC106 expression.This expression dysregulation was further confirmed using 10 samples from our cohort,which exhibited the same HPV-CCDC106 integration.In summary,we found that HPV-CCDC106 inte-gration altered local chromosome architecture and hijacked an enhancer via 3D genome structure remodeling.Thus,this study provides insight into the 3D structural mechanism underlying HPV inte-gration in cervical carcinogenesis.