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

引用

Journal of Genetics and Genomics 2020年第8期47卷 435-448页

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 Department of Gynecologic Oncology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Cancer Biology Research Center(Key Laboratory of the Ministry of Education) Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China National Key Laboratory of Crop Genetic Improvement Huazhong Agricultural UniversityWuhan430070China Agricultural Bioinformatics Key Laboratory of Hubei Province Hubei Engineering Technology Research Center of Agricultural Big DataCollege of InformaticsHuazhong Agricultural UniversityWuhan430070China State Key Laboratory of Agricultural Microbiology Huazhong Agricultural UniversityWuhan430070China Bio-Medical Center Huazhong Agricultural UniversityWuhan430070China College of Veterinary Medicine Huazhong Agricultural UniversityWuhan430070China Department of Obstetrics and Gynecology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Department of Obstetrics and Gynecology Key Laboratory for Molecular Diagnosis of Hubei ProvinceThe Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430010China Department of Computational and Systems Biology Genome Institute of SingaporeSingapore Department of Gynecological Oncology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou510080China

integration of human papillomavirus(hpv)DNA into the human genome is a reputed key driver of cervical ***,the effects of hpv integration on chromatin structural organization and gene expression are largely *** studied a cohort of 61 samples and identified an integration hot spot in the CCDC106 gene on chromosome *** 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 *** analyses indicated that chromosome 19 exhibited significant genomic variation and differential expression densities,with correlation found between three-dimensional(3D)structural change and gene ***,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 dysregulation was further confirmed using 10 samples from our cohort,which exhibited the same hpv-CCDC106 *** summary,we found that hpv-CCDC106 integration altered local chromosome architecture and hijacked an enhancer via 3D genome structure ***,this study provides insight into the 3D structural mechanism underlying hpv integration in cervical carcinogenesis.

关键词： Cervical cancer hpv integration Fusion gene Hi-C Enhancer TAD

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