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Órgano Oficial de la Asociación Mexicana de Hepatología

2017, Number 4

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Ann Hepatol 2017; 16 (4)

Retinoid X Receptor α-Dependent HBV Minichromosome Remodeling and Viral Replication

Zhang Y, He S, Guo Jin-Jun, Peng H, Fan Jia-Hao, Li Qing-Ling

Language: English
References: 30
Page: 501-509
PDF size: 267.86 Kb.


ABSTRACT

Background and aim. The HBV covalently closed circular DNA (cccDNA) is organized into a minichromosome in the nuclei of infected hepatocytes through interactions with histone and nonhistone proteins. Retinoid X receptor α (RXRα), a liver-enriched nuclear receptor, participates in regulation of HBV replication and transcription through modulation of HBV enhancer 1 and core promoter activity. Material and methods. This study investigated RXRα involvement in HBV cccDNA epigenetic modifications. Quantitative cccDNA chromatin immunoprecipitation (ChIP) was applied to study the recruitment of RXRα, histones, and chromatin- modifying enzymes to HBV minichromosome in HepG2 cells after transfection of the linear HBV genome. Results. RXRα was found to directly bind to HBV cccDNA; recruitment of RXRα to HBV mini-chromosome paralleled HBV replication, histone recruitment, and histone acetylation in HBVcccDNA. Moreover, RXRα overexpression or knock-down significantly increased or impaired the recruitment of the p300 acetyltransferase to cccDNAminichromosome. Conclusions. Our results confirmed the regulation of RXRα on HBV replication in vitro and demonstrated the modulation of RXRα on HBV cccDNA epigenetics. These findings provide a profound theoretical and experimental basis for late-model antiviral treatment acting on the HBV cccDNA and minichromosome.


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