Transcriptionally inactive hepatitis B virus episome DNA preferentially resides in the vicinity of chromosome 19 in 3D host genome upon infection
Dingbin Tang,
Hanqing Zhao,
Yumeng Wu,
Bo Peng,
Zhenchao Gao,
Yinyan Sun,
Jinzhi Duan,
Yonghe Qi,
Yunfei Li,
Zhongmin Zhou,
Guilan Guo,
Yu Zhang,
Cheng Li,
Jianhua Sui,
Wenhui Li
Affiliations
Dingbin Tang
Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, Peking University, Beijing, China; National Institute of Biological Sciences, Beijing, China
Hanqing Zhao
National Institute of Biological Sciences, Beijing, China
Yumeng Wu
Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, Peking University, Beijing, China; National Institute of Biological Sciences, Beijing, China
Bo Peng
Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, Peking University, Beijing, China; National Institute of Biological Sciences, Beijing, China
Zhenchao Gao
National Institute of Biological Sciences, Beijing, China
Yinyan Sun
National Institute of Biological Sciences, Beijing, China
Jinzhi Duan
National Institute of Biological Sciences, Beijing, China
Yonghe Qi
National Institute of Biological Sciences, Beijing, China
Yunfei Li
National Institute of Biological Sciences, Beijing, China
Zhongmin Zhou
College of Life Sciences, Beijing Normal University, Beijing, China; National Institute of Biological Sciences, Beijing, China
Guilan Guo
College of Life Sciences, Beijing Normal University, Beijing, China; National Institute of Biological Sciences, Beijing, China
Yu Zhang
National Institute of Biological Sciences, Beijing, China
Cheng Li
School of Life Sciences, Center for Statistical Science, Center for Bioinformatics, Peking University, Beijing, China
Jianhua Sui
National Institute of Biological Sciences, Beijing, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China
Wenhui Li
National Institute of Biological Sciences, Beijing, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China; Corresponding author
Summary: The hepatitis B virus (HBV) infects 257 million people worldwide. HBV infection requires establishment and persistence of covalently closed circular (ccc) DNA, a viral episome, in nucleus. Here, we study cccDNA spatial localization in the 3D host genome by using chromosome conformation capture-based sequencing analysis and fluorescence in situ hybridization (FISH). We show that transcriptionally inactive cccDNA is not randomly distributed in host nucleus. Rather, it is preferentially accumulated at specialized areas, including regions close to chromosome 19 (chr.19). Activation of the cccDNA is apparently associated with its re-localization, from a pre-established heterochromatin hub formed by 5 regions of chr.19 to transcriptionally active regions formed by chr.19 and nearby chromosomes including chr.16, 17, 20, and 22. This active versus inactive positioning at discrete regions of the host genome is primarily controlled by the viral HBx protein and by host factors including the structural maintenance of chromosomes protein 5/6 (SMC5/6) complex.
