Format

Send to

Choose Destination
Epigenetics Chromatin. 2018 Jun 22;11(1):34. doi: 10.1186/s13072-018-0204-2.

Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx.

Author information

1
Department of Pediatrics, HELIOS University Hospital Wuppertal, Centre for Clinical and Translational Research (CCTR), Faculty of Health, Centre for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Heusnerstr. 40, 42283, Wuppertal, Germany.
2
Department of Paediatric Gastroenterology, Hepatology and Nutrition, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge,, CB2 0QQ, UK.
3
Department of Pediatrics, HELIOS University Hospital Wuppertal, Centre for Clinical and Translational Research (CCTR), Faculty of Health, Centre for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Heusnerstr. 40, 42283, Wuppertal, Germany. jan.postberg@uni-wh.de.
4
Clinical Molecular Genetics and Epigenetics, Faculty of Health, School of Medicine, Centre for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Alfred-Herrhausen-Str. 50, 58448, Witten, Germany. jan.postberg@uni-wh.de.

Abstract

BACKGROUND:

In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of cccDNA and HBx remains unexplored.

RESULTS:

To identify virus-host genome interactions and the underlying nuclear landscape for the first time, we combined circular chromosome conformation capture (4C) with RNA-seq and ChIP-seq. Moreover, we studied HBx-binding to HBV episomes. In HBV-positive HepaRG hepatocytes, we observed preferential association of HBV episomes and HBx with actively transcribed nuclear domains on the host genome correlating in size with constrained topological units of chromatin. Interestingly, HBx alone occupied transcribed chromatin domains. Silencing of native HBx caused reduced episomal HBV stability.

CONCLUSIONS:

As part of the HBV episome, HBx might stabilize HBV episomal nuclear localization. Our observations may contribute to the understanding of long-term episomal stability and the facilitation of viral persistence. The exact mechanism by which HBx contributes to HBV nuclear persistence warrants further investigations.

KEYWORDS:

Chromatin fiber loops; Epigenome; Episome; HBxAg; Host–pathogen interaction; Oncogene; Supranucleosomal structure; TADs; Transcription factories; X-protein

PMID:
29933745
PMCID:
PMC6015472
DOI:
10.1186/s13072-018-0204-2
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center