肝受体同源物-1/人B1因子和肝细胞核因子1协同上调乙型肝炎病毒基因转录和DNA复制。

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

作者信息

Cai Yan Ning, Zhou Qing, Kong Yu Ying, Li Mei, Viollet Benoit, Xie You Hua, Wang Yuan

机构信息

State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

出版信息

Cell Res. 2003 Dec;13(6):451-8. doi: 10.1038/sj.cr.7290187.

DOI:10.1038/sj.cr.7290187

PMID:14728801

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, 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.

摘要

增强子II（ENII）是乙肝病毒（HBV）基因组中肝病毒基因转录和DNA复制的关键顺式元件之一。ENII的肝脏特异性活性受多种肝脏富集转录因子调控，包括LRH-1/hB1F、HNF1、HNF3β、HNF4和C/EBP。关于这些重要因子之间相互作用的知识仍然有限。在本研究中，我们证明了孤儿核受体LRH-1/hB1F和同源蛋白HNF1在上调ENII的肝脏特异性活性方面存在功能协同作用。这种协同作用足以在非肝细胞中启动病毒基因转录和DNA复制。我们已经确定了hB1F和HNF1中有助于协同作用的激活结构域。我们进一步表明，hB1F和HNF1在体外可以直接相互作用，并绘制了这种相互作用所需的结构域。