REGULAR ARTICLES

Cell Research (2003); 13(6):451-458

LRH-1/hB1F and HNF1 synergistically up-regulate hepatitis B virus gene transcription and DNA replication

an Ning CAI¹, Qing ZHOU¹, Yu Ying KONG¹, Mei LI^1*, Benoit VIOLLET^2**, You Hua XIE^1*, Yuan WANG^{1* 1}State 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
²Oncogenic Viruses Unit, Department of Biotechnology, Institut Pasteur, Paris, France ^*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 Apr-4-2003 Revised Sep-15-2003 Accepted Sep-25-2003

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.

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, HNF3b, 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.
Key words: LRH-1/hB1F, HNF1, HBV, ENII, synergism.