LRH-1/hB1F and HNF1 synergistically up-regulate hepatitis B virus gene transcription and DNA replication.
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.
Cai
Yan Ning
YN
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Zhou
Qing
Q
Kong
Yu Ying
YY
Li
Mei
M
Viollet
Benoit
B
Xie
You Hua
YH
Wang
Yuan
Y
D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular; D002374:Catalase / Q000032:analysis; D004261:DNA Replication; D004268:DNA-Binding Proteins; D015967:Gene Expression Regulation, Viral; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D009687:Nuclear Proteins; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017384:Sequence Deletion; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; C082631:NR5A2 protein, human; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D002374:Catalase; D005982:Glutathione Transferase