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KAT2A Promotes Hepatitis B Virus Transcription and Replication Through Epigenetic Regulation of cccDNA Minichromosome

Authors :
Yi-Ping Qin
Hai-Bo Yu
Si-Yu Yuan
Zhen Yang
Fang Ren
Qing Wang
Fan Li
Ji-Hua Ren
Sheng-Tao Cheng
Yu-Jiao Zhou
Xin He
Hong-Zhong Zhou
Yuan Zhang
Ming Tan
Min-Li Yang
Da-Peng Zhang
Xu Wen
Mei-Ling Dong
Hui Zhang
Jing Liu
Zhi-Hong Li
Yao Chen
Ai-Long Huang
Wei-Xian Chen
Juan Chen
Source :
Frontiers in Microbiology, Vol 12 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

Hepatitis B virus (HBV) infection remains a major health problem worldwide. Sufficient maintenance of the HBV covalently closed circular DNA (cccDNA), which serves as a template for HBV transcription, is responsible for the failure of antiviral therapies. While accumulating evidence suggests that cccDNA transcription is regulated by epigenetic machinery, particularly the acetylation and methylation of cccDNA-bound histone 3 (H3) and histone 4 (H4), the potential contributions of histone succinylation and related host factors remain obscured. Here, by screening a series of succinyltransferases and desuccinylases, we identified KAT2A as an important host factor of HBV transcription and replication. By using HBV-infected cells and mouse models with HBV infection, KAT2A was found to affect the transcriptional activity of cccDNA but did not affect cccDNA production. Mechanism studies showed that KAT2A is mainly located in the nucleus and could bind to cccDNA through interaction with HBV core protein (HBc). Moreover, we confirmed histone H3K79 succinylation (H3K79succ) as a histone modification on cccDNA minichromosome by using the cccDNA ChIP-Seq approach. Importantly, KAT2A silencing specifically reduced the level of cccDNA-bound succinylated H3K79. In conclusion, KAT2A promotes HBV transcription and replication through epigenetic machinery, and our findings may provide new insight into the treatment of HBV infection.

Details

Language :
English
ISSN :
1664302X
Volume :
12
Database :
Directory of Open Access Journals
Journal :
Frontiers in Microbiology
Publication Type :
Academic Journal
Accession number :
edsdoj.1079347fd2124e00b364332ac6f3168b
Document Type :
article
Full Text :
https://doi.org/10.3389/fmicb.2021.795388