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Functional analysis of ground squirrel hepatitis virus enhancer II
G Fourel1, F Ringeisen, M Flajolet
1Unité de Recombinaison et Expression Génétique, INSERM U163, Institut Pasteur, Paris, France.
Journal of Virology
|January 28, 1998
Summary
Researchers identified a key regulatory element in ground squirrel hepatitis virus (GSHV) that controls gene transcription. This element, similar to woodchuck hepatitis virus (WHV) enhancer II, shows conserved binding sites for important liver transcription factors.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Hepatitis viruses like GSHV and WHV possess regulatory elements controlling viral gene expression.
- Understanding these elements is crucial for comprehending viral replication and pathogenesis.
Purpose of the Study:
- To characterize a major regulatory element (Ge2) in the ground squirrel hepatitis virus (GSHV) core promoter.
- To compare the organization and function of Ge2 with woodchuck hepatitis virus (WHV) enhancer II (We2).
Main Methods:
- Transient transfection assays in human hepatoma cells.
- Analysis of transcription factor binding sites within the regulatory elements.
- Comparative analysis of GSHV Ge2 and WHV We2 activity and organization.
Main Results:
- The GSHV element (Ge2) stimulates transcription from viral and heterologous promoters in an orientation-independent manner.
- Ge2 shares conserved binding sites with We2 for liver-enriched factors (HNF-1, HNF-4) and ubiquitous factors (NF1, Oct).
- Ge2 exhibits distinct features, including binding C/EBP factors and differential HNF-4 binding affinities, resulting in lower activity than We2.
Conclusions:
- HNF-1 and HNF-4 are essential for the liver-specific transcriptional activity of both GSHV and WHV core promoters.
- The conserved organization of Ge2 and We2 highlights the importance of these transcription factors in hepadnavirus regulation.
- Distinctive features of Ge2 contribute to its lower transcriptional activity compared to We2.