Regulation of hepatitis B virus expression in progenitor and differentiated cell types: Evidence for negative transcriptional control in nonpermissive cells

Michael Ott, Qiangzhong Ma, Baiquan Li, S. Gagandeep, Leslie E. Rogler, Sanjeev Gupta

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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 Hepal-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.

Original languageEnglish (US)
Pages (from-to)175-186
Number of pages12
JournalGene expression
Volume8
Issue number3
StatePublished - 1999

Keywords

  • Gene expression
  • Hepatitis B virus
  • Liver
  • Stem cell
  • Transcription factor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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