SIRT7 restricts HBV transcription and replication through catalyzing desuccinylation of histone H3 associated with cccDNA minichromosome

被引：34

作者：

Yu, Hai-Bo ^{[1
]}

Cheng, Sheng-Tao ^{[1
]}

Ren, Fang ^{[1
]}

Chen, Yong ^{[2
]}

Shi, Xiao-Feng ^{[1
]}

Wong, Vincent Kam Wai ^{[3
]}

Law, Betty Yuen Kwan ^{[3
]}

Ren, Ji-Hua ^{[1
]}

Zhong, Shan ^{[1
]}

Chen, Wei-Xian ^{[4
]}

Xu, Hong-Mei ^{[5
]}

Zhang, Zhen-Zhen ^{[5
]}

Hu, Jie-Li ^{[1
]}

Cai, Xue-Fei ^{[1
]}

Hu, Yuan ^{[1
]}

Zhang, Wen-Lu ^{[1
]}

Long, Quan-Xin ^{[1
]}

He, Lin ^{[1
]}

Hu, Zhong-Wen ^{[1
]}

Jiang, Hui ^{[1
]}

Zhou, Hong-Zhong ^{[1
]}

Huang, Ai-Long ^{[1
]}

Chen, Juan ^{[1
]}

机构：

[1] Chongqing Med Univ, Key Lab Mol Biol Infect Dis Designated, Chinese Minist Educ, Chongqing, Peoples R China

[2] Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobliliary Surg, Chongqing, Peoples R China

[3] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R China

[4] Chongqing Med Univ, Dept Clin Lab, Affiliated Hosp 2, Chongqing, Peoples R China

[5] Chongqing Med Univ, Dept Infect Dis, Childrens Hosp, Chongqing, Peoples R China

来源：

CLINICAL SCIENCE | 2021年 / 135卷 / 12期

基金：

中国国家自然科学基金;

关键词：

B-VIRUS REPLICATION; RNA-POLYMERASE-I; EPIGENETIC REGULATION; SIRTUINS; ACETYLATION; REPRESSION; DEACETYLASE; INHIBITION; STRESS;

D O I：

10.1042/CS20210392

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Chronic hepatitis B virus (HBV) infection is a significant public health burden worldwide. HBV covalently closed circular DNA (cccDNA) organized as a minichromosome in nucleus is responsible for viral persistence and is the key obstacle for a cure of chronic hepatitis B (CHB). Recent studies suggest cccDNA transcription is epigenetically regulated by histone modifications, especially histone acetylation and methylation. In the present study, we identified transcriptionally active histone succinylation (H3K122succ) as a new histone modification on cccDNA minichromosome by using cccDNA ChIP-Seq approach. Silent mating type information regulation 2 homolog 7 (SIRT7), as an NAD+-dependent histone desuccinylase, could bind to cccDNA through interaction with HBV core protein where it catalyzed histone 3 lysine 122 (H3K122) desuccinylation. Moreover, SIRT7 acts cooperatively with histone methyltransferase, suppressor of variegation 3-9 homolog 1 (SUV39H1) and SET domain containing 2 (SETD2) to induce silencing of HBV transcription through modulation of chromatin structure. Our data improved the understanding of histone modifications of the cccDNA minichromosome, thus transcriptional silencing of cccDNA may represent a novel antiviral strategy for the prevention or treatment of HBV infection.

引用

页码：1505 / 1522

页数：18

共 41 条

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