ABSTRACT
Enhancer II (ENII) is one of the critical cis-elements in the Hepatitis B Virus (HBV) genome for the hepatic viral gene transcription and DNA replication. The liver-specific activity of ENII is regulated by multiple liver-enriched transcription factors, including LRH-1/hB1F, HNF1, HNF3β, HNF4 and C/EBP. Knowledge on the interplay of these important factors is still limited. In this study, we demonstrate a functional synergism between the orphan nuclear receptor LRH-1/hB1F and the homeoprotein HNF1 in up-regulating the liver-specific activity of ENII. This synergism is sufficient for initiating the viral gene transcription and DNA replication in non-hepatic cells. We have defined the activation domains in hB1F and HNF1 that contribute to the synergism. We further show that hB1F and HNF1 can interact directly in vitro and have mapped the domains required for this interaction.
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Abbreviations
- hB1F:
-
hepatitis B virus enhancer II B1 binding factor
- LRH-1:
-
liver receptor homologue-1
- HNF1:
-
hepatocyte nuclear factor 1
- HBV:
-
hepatitis B virus
- Cp:
-
core promoter
- ENII:
-
enhancer II
- AD:
-
activation domain
- DBD:
-
DNA binding domain
- LBD:
-
ligand binding domain
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Acknowledgements
The authors are grateful to Dr. E Lai for the pCMVpoly vector, Dr. M YANIV for the HNF1 expression plasmid and Dr. XM Yu for the pWT. This work is supported by the National Natural Science Foundation of China (30100088), High Technology Research and Development Project (2001-AA221261) and Basic Research Program from Ministry of Science and Technology (G19990 54105). Y Xie is supported by a Qi Ming Xing program (01QA14046) from Shanghai Science and Technology Committee. M Li is supported by a fellowship for outstanding Ph.D students from the Chinese Academy of Sciences.
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CAI, Y., ZHOU, Q., KONG, Y. et al. LRH-1/hB1F and HNF1 synergistically up-regulate hepatitis B virus gene transcription and DNA replication. Cell Res 13, 451–458 (2003). https://doi.org/10.1038/sj.cr.7290187
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DOI: https://doi.org/10.1038/sj.cr.7290187
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