Transcriptionally inactive hepatitis B virus episome DNA preferentially resides in the vicinity of chromosome 19 in 3D host genome upon infection

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 capt...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2021-06-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124721006598
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author 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
author_facet 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
author_sort Dingbin Tang
collection DOAJ
description 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.
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spelling doaj.art-f10902dffb3d412496b93589006a0e642022-12-21T22:41:24ZengElsevierCell Reports2211-12472021-06-013513109288Transcriptionally inactive hepatitis B virus episome DNA preferentially resides in the vicinity of chromosome 19 in 3D host genome upon infectionDingbin Tang0Hanqing Zhao1Yumeng Wu2Bo Peng3Zhenchao Gao4Yinyan Sun5Jinzhi Duan6Yonghe Qi7Yunfei Li8Zhongmin Zhou9Guilan Guo10Yu Zhang11Cheng Li12Jianhua Sui13Wenhui Li14Peking 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, ChinaNational Institute of Biological Sciences, Beijing, ChinaPeking 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, ChinaPeking 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, ChinaNational Institute of Biological Sciences, Beijing, ChinaNational Institute of Biological Sciences, Beijing, ChinaNational Institute of Biological Sciences, Beijing, ChinaNational Institute of Biological Sciences, Beijing, ChinaNational Institute of Biological Sciences, Beijing, ChinaCollege of Life Sciences, Beijing Normal University, Beijing, China; National Institute of Biological Sciences, Beijing, ChinaCollege of Life Sciences, Beijing Normal University, Beijing, China; National Institute of Biological Sciences, Beijing, ChinaNational Institute of Biological Sciences, Beijing, ChinaSchool of Life Sciences, Center for Statistical Science, Center for Bioinformatics, Peking University, Beijing, ChinaNational Institute of Biological Sciences, Beijing, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, ChinaNational Institute of Biological Sciences, Beijing, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124721006598HBV3D host genomespatial localizationchromosome 19episomal DNAHBx protein
spellingShingle 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
Transcriptionally inactive hepatitis B virus episome DNA preferentially resides in the vicinity of chromosome 19 in 3D host genome upon infection
Cell Reports
HBV
3D host genome
spatial localization
chromosome 19
episomal DNA
HBx protein
title Transcriptionally inactive hepatitis B virus episome DNA preferentially resides in the vicinity of chromosome 19 in 3D host genome upon infection
title_full Transcriptionally inactive hepatitis B virus episome DNA preferentially resides in the vicinity of chromosome 19 in 3D host genome upon infection
title_fullStr Transcriptionally inactive hepatitis B virus episome DNA preferentially resides in the vicinity of chromosome 19 in 3D host genome upon infection
title_full_unstemmed Transcriptionally inactive hepatitis B virus episome DNA preferentially resides in the vicinity of chromosome 19 in 3D host genome upon infection
title_short Transcriptionally inactive hepatitis B virus episome DNA preferentially resides in the vicinity of chromosome 19 in 3D host genome upon infection
title_sort transcriptionally inactive hepatitis b virus episome dna preferentially resides in the vicinity of chromosome 19 in 3d host genome upon infection
topic HBV
3D host genome
spatial localization
chromosome 19
episomal DNA
HBx protein
url http://www.sciencedirect.com/science/article/pii/S2211124721006598
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