The CCCTC-binding factor CTCF represses hepatitis B virus enhancer I and regulates viral transcription.
Binding Sites
CCCTC-Binding Factor
/ physiology
Cell Line
Chromatin
/ metabolism
Chromatin Immunoprecipitation
DNA, Viral
/ metabolism
Enhancer Elements, Genetic
Epigenomics
Gene Expression Regulation, Viral
Hep G2 Cells
Hepatitis B
/ virology
Hepatitis B virus
/ physiology
Humans
Mutation
RNA, Viral
Viral Transcription
Virus Replication
CTCF
HBV
epigenetics
transcription insulation
transcription regulation
Journal
Cellular microbiology
ISSN: 1462-5822
Titre abrégé: Cell Microbiol
Pays: India
ID NLM: 100883691
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
05
08
2020
revised:
09
09
2020
accepted:
29
09
2020
pubmed:
3
10
2020
medline:
12
10
2021
entrez:
2
10
2020
Statut:
ppublish
Résumé
Hepatitis B virus (HBV) infection is of global importance with over 2 billion people exposed to the virus during their lifetime and at risk of progressive liver disease, cirrhosis and hepatocellular carcinoma. HBV is a member of the Hepadnaviridae family that replicates via episomal copies of a covalently closed circular DNA (cccDNA) genome. The chromatinization of this small viral genome, with overlapping open reading frames and regulatory elements, suggests an important role for epigenetic pathways to regulate viral transcription. The chromatin-organising transcriptional insulator protein, CCCTC-binding factor (CTCF), has been reported to regulate transcription in a diverse range of viruses. We identified two conserved CTCF binding sites in the HBV genome within enhancer I and chromatin immunoprecipitation (ChIP) analysis demonstrated an enrichment of CTCF binding to integrated or episomal copies of the viral genome. siRNA knock-down of CTCF results in a significant increase in pre-genomic RNA levels in de novo infected HepG2 cells and those supporting episomal HBV DNA replication. Furthermore, mutation of these sites in HBV DNA minicircles abrogated CTCF binding and increased pre-genomic RNA levels, providing evidence of a direct role for CTCF in repressing HBV transcription.
Identifiants
pubmed: 33006186
doi: 10.1111/cmi.13274
pmc: PMC7116737
mid: EMS115918
doi:
Substances chimiques
CCCTC-Binding Factor
0
CTCF protein, human
0
Chromatin
0
DNA, Viral
0
RNA, Viral
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13274Subventions
Organisme : Medical Research Council
ID : MR/R022011/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 200838/Z/16/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 200838
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T015985/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0801976
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400802
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N023498/1
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.
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