Induction of hepatitis B virus core gene in human cells by cytosine demethylation in the promoter.
A recombinant human cell line constructed by transfection of epithelial cells with a plasmid containing the hepatitis B virus core gene (HBc) was used to study the regulation of HBc gene expression. Methylation of a single Hpa II site 280 base pairs upstream from the structural gene was found to regulate the expression of the core gene. Expression increased in cells treated with 5'-azacytidine as a result of cytosine demethylation at this site, and there was a fivefold increase in the number of HBc gene transcripts in total cellular messenger RNA. The varied life cycle of hepatitis B virus in disease such as viral hepatitis and liver cancer may therefore be attributable to the site-specific regulation of the gene involved in replication of the viral DNA and to the cytophathic effects elicited by this gene in human cells.
Korba
B E
BE
Wilson
V L
VL
Yoakum
G H
GH
D044503:5-Methylcytosine; D001374:Azacitidine / Q000494:pharmacology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004262:DNA Restriction Enzymes; D004279:DNA, Viral / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005814:Genes, Viral; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006801:Humans; D008745:Methylation; D011401:Promoter Regions, Genetic; D013997:Time Factors; D014158:Transcription, Genetic; D014779:Virus Replication
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D044503:5-Methylcytosine; D003596:Cytosine; D004262:DNA Restriction Enzymes; D001374:Azacitidine