Two lines of HBV transgenic mice (derived from G7 and G26) have been produced, each of which contains a unique locus of HBV DNA and expresses 2.1-kb HBsAg transcripts preferentially in liver and kidney tissues. To investigate the regulation of HBV expression in these mice, we have examined the state of methylation and the chromatin structure in and around the HBV sequences in tissues with and without HBV gene expression. Hypomethylation of Hpall and Hhal sites in and around the HBV sequences strongly correlated with HBV gene expression, although it was clearly not sufficient for HBV expression. Alterations in chromatin configuration were detected by DNase I digestion which identified a major hypersensitive site (HS) in liver and kidney tissue. By restriction enzyme mapping and indirect end-labeling, the HS was localized to the region of the HBV enhancer in both lines of HBV transgenics. The presence of this DNase I hypersensitive site was necessary but not sufficient for HBV expression, since it was also detected in tissues not expressing HBV. An additional DNase I hypersensitive site was mapped to the core promoter region of the G7 transgene in liver and kidney tissue but not in G26 tissues. The identification of a DNase I hypersensitive site mapping to the HBV enhancer region supports the notion that this region can interact with cellular proteins and is involved in the regulation of viral gene transcription in vivo.
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