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-...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/hB 1 F,HNF 1,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/hB 1F 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 hB 1F and HNF 1 that contribute to the synergism.We further show that hB 1F and HNF1 can interact directly in vitro and have mapped the domains required for this interaction.展开更多
基金supported by the National Natural Science Foundation of China(30100088)High Technology Research and Development Project(2001-AA221261)+1 种基金Basic Research Program from Ministry of Science and Technology(G1999054105)supported by a Qi Ming Xing program(01QA14046)from Shanghai Science and Technology Committee
文摘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/hB 1 F,HNF 1,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/hB 1F 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 hB 1F and HNF 1 that contribute to the synergism.We further show that hB 1F and HNF1 can interact directly in vitro and have mapped the domains required for this interaction.
