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Regulation of Hepatitis B Virus Expression in Progenitor and Differentiated Cell Types: Evidence for Negative Transcriptional Control in Nonpermissive Cells

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Mechanisms regulating cell type-specific gene expression are not completely understood. We utilized hepatitis B virus (HBV) enhancer I and preS1 promoter sequences, which exhibit cell type specificity, to analyze transcriptional control in pluripotential murine embryonic stem (ES) cells, bipotential HBC-3 progenitor liver cells, mature hepatocytes, and fibroblasts. In transient transfection assays, HBV sequences were most active in primary hepatocytes, followed by HBC-3 and ES cells, and became inactive in fibroblasts. Cotransfections with HNF-3 or C/EBP plasmids increased expression of HBV sequences in hepatocytes and HBC-3 cells. However, increased HBV expression was not observed in ES cells and HBV remained inactive in fibroblasts, suggesting different transcriptional controls, which was compatible with alterations in the abundance of endogenous transcription factors. Analysis in somatic hybrid cells created from NIH 3T3 fibroblasts and Hepa1-6 mouse hepatocytes with expression of albumin and selected hepatic transcription factors showed that HBV sequences were expressed weakly but without increased expression following transfection of HNF-1, HNF-3, and C/EBP plasmids. These findings indicated that repression of HBV in nonpermissive cells involved inactivation of transcription factor activity. Expression of HBV in stem cells is relevant for mechanisms concerning viral persistence and oncogenesis, as well as analysis of hepatocytic differentiation in progenitor cells.
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Keywords: Gene expression; Hepatitis B virus; Liver; Stem cell; Transcription factor

Document Type: Research Article

Publication date: January 1, 1999

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  • Gene Expression, The Journal of Liver Research will publish articles in all aspects of hepatology. Hepatology, as a research discipline, has seen unprecedented growth especially in the cellular and molecular mechanisms of hepatic health and disease, which continues to have a major impact on understanding liver development, stem cells, carcinogenesis, tissue engineering, injury, repair, regeneration, immunology, metabolism, fibrosis, and transplantation. Continued research and improved understanding in these areas will have a meaningful impact on liver disease prevention, diagnosis, and treatment. The existing journal Gene Expression has expanded its focus to become Gene Expression, The Journal of Liver Research to meet this growing demand. In its revised and expanded scope, the journal will publish high-impact original articles, reviews, short but complete articles, and special articles (editorials, commentaries, opinions) on all aspects of hepatology, making it a unique and invaluable resource for readers interested in this field. The expanded team, led by an Editor-in-Chief who is uniquely qualified and a renowned expert, along with a dynamic and functional editorial board, is determined to make this a premier journal in the field of hepatology.
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