1. ¹State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; E-mail: wangy@sibs.ac.cn
2. ²Oncogenic Viruses Unit, Department of Biotechnology, Institut Pasteur, Paris, France

Correspondence: Prof. Yuan WANG, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Tel : 86-21-54921103 Fax: 86-21-54921011 E-mail: wangy@sibs.ac.cn; Youhua XIE, E-mail: yhxie@sibs.ac.cn

^*Current address: Institut Cochin, Departement GDPM, Paris, France

^**Current address: I.G.B.M.C., I'rue Laurent Fries, B.P.163, Illkirch CEDEX, Strasbourg, France

Received 4 April 2003; Revised 15 September 2003; Accepted 25 September 2003.

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, HNF3, 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.