PMID- 34192543
OWN - NLM
STAT- MEDLINE
DCOM- 20220210
LR  - 20220210
IS  - 2211-1247 (Electronic)
VI  - 35
IP  - 13
DP  - 2021 Jun 29
TI  - Transcriptionally inactive hepatitis B virus episome DNA preferentially resides 
      in the vicinity of chromosome 19 in 3D host genome upon infection.
PG  - 109288
LID - S2211-1247(21)00659-8 [pii]
LID - 10.1016/j.celrep.2021.109288 [doi]
AB  - 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.
CI  - Copyright (c) 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Tang, Dingbin
AU  - Tang D
AD  - 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.
FAU - Zhao, Hanqing
AU  - Zhao H
AD  - National Institute of Biological Sciences, Beijing, China.
FAU - Wu, Yumeng
AU  - Wu Y
AD  - 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.
FAU - Peng, Bo
AU  - Peng B
AD  - 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.
FAU - Gao, Zhenchao
AU  - Gao Z
AD  - National Institute of Biological Sciences, Beijing, China.
FAU - Sun, Yinyan
AU  - Sun Y
AD  - National Institute of Biological Sciences, Beijing, China.
FAU - Duan, Jinzhi
AU  - Duan J
AD  - National Institute of Biological Sciences, Beijing, China.
FAU - Qi, Yonghe
AU  - Qi Y
AD  - National Institute of Biological Sciences, Beijing, China.
FAU - Li, Yunfei
AU  - Li Y
AD  - National Institute of Biological Sciences, Beijing, China.
FAU - Zhou, Zhongmin
AU  - Zhou Z
AD  - College of Life Sciences, Beijing Normal University, Beijing, China; National 
      Institute of Biological Sciences, Beijing, China.
FAU - Guo, Guilan
AU  - Guo G
AD  - College of Life Sciences, Beijing Normal University, Beijing, China; National 
      Institute of Biological Sciences, Beijing, China.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - National Institute of Biological Sciences, Beijing, China.
FAU - Li, Cheng
AU  - Li C
AD  - School of Life Sciences, Center for Statistical Science, Center for 
      Bioinformatics, Peking University, Beijing, China.
FAU - Sui, Jianhua
AU  - Sui J
AD  - National Institute of Biological Sciences, Beijing, China; Tsinghua Institute of 
      Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.
FAU - Li, Wenhui
AU  - Li W
AD  - National Institute of Biological Sciences, Beijing, China; Tsinghua Institute of 
      Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China. 
      Electronic address: liwenhui@nibs.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (DNA, Viral)
RN  - 0 (Heterochromatin)
SB  - IM
MH  - Base Sequence
MH  - Cells, Cultured
MH  - Chromosomes, Human, Pair 19/*genetics
MH  - DNA, Viral/genetics
MH  - *Genome, Human
MH  - Genome, Viral
MH  - Hep G2 Cells
MH  - Hepatitis B/*genetics/*virology
MH  - Hepatitis B virus/*genetics
MH  - Hepatocytes/pathology/virology
MH  - Heterochromatin/metabolism
MH  - Humans
MH  - Plasmids/*genetics
MH  - *Transcription, Genetic
OTO - NOTNLM
OT  - 3D host genome
OT  - HBV
OT  - HBx protein
OT  - cccDNA
OT  - chromosome 19
OT  - circularized chromosome conformation capture (4C) sequencing analysis
OT  - episomal DNA
OT  - fluorescence in situ hybridization (FISH)
OT  - in situ Hi-C analysis
OT  - spatial localization
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2021/07/01 06:00
MHDA- 2022/02/11 06:00
CRDT- 2021/06/30 20:19
PHST- 2020/03/13 00:00 [received]
PHST- 2021/03/07 00:00 [revised]
PHST- 2021/06/02 00:00 [accepted]
PHST- 2021/06/30 20:19 [entrez]
PHST- 2021/07/01 06:00 [pubmed]
PHST- 2022/02/11 06:00 [medline]
AID - S2211-1247(21)00659-8 [pii]
AID - 10.1016/j.celrep.2021.109288 [doi]
PST - ppublish
SO  - Cell Rep. 2021 Jun 29;35(13):109288. doi: 10.1016/j.celrep.2021.109288.