Members of the nuclear receptor superfamily regulate transcription from the hepatitis B virus nucleocapsid promoter
Members of the nuclear receptor superfamily regulate transcription from the hepatitis B virus nucleocapsid promoter
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DOI：
10.1128/jvi.71.2.1058-1071.1997
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发表时间：
1997-02-01
影响因子：
5.4
通讯作者：
McLachlan, A
中科院分区：
文献类型：
--
作者：
Raney, AK;Johnson, JL;McLachlan, A
研究了转录因子核受体超家族成员在调节乙型肝炎病毒（HBV）转录中的作用。在去分化肝癌细胞系HepG2.1中，通过瞬时转染分析，研究了肝细胞核因子4 （HNF4）、类视黄醇X受体（RXR）和过氧化物酶体增殖激活受体（PPAR）调节四种HBV启动子转录活性水平的能力。结果发现，HNF4存在时，核衣壳和大表面抗原启动子被反激活，而RXR和PPAR存在时，增强子I/X基因、核衣壳和大表面抗原启动子被反激活。对与核衣壳启动子区相互作用的核受体的表征表明，HNF4是结合在跨越核苷酸-127至-102的调控区域上的主要转录因子，而HNF4、RXR-PPAR异源二聚体、COUPTF1和ARP1结合在跨越核苷酸-34至-7的调控区域上。HNF4对核衣壳启动子的转录激活似乎是通过启动子中的两个HNF4结合位点介导的，而RXR-PPAR对核衣壳启动子转录水平的调节似乎是由跨越核苷酸-34至-7和HBV增强子1区域的调控序列元件调节的。这些观察结果表明，HBV转录，特别是基因组前RNA合成，是由配体依赖性核受体调节的。能够调节这些核受体活性的激动剂和拮抗剂可能允许在病毒感染期间调节HBV转录和随后的复制。
The role of members of the nuclear receptor superfamily of transcription factors in regulating hepatitis B virus (HBV) transcription was investigated. Hepatocyte nuclear factor 4 (HNF4), the retinoid X receptor (RXR), and the peroxisome proliferator-activated receptor (PPAR) were examined for their capacity to modulate the level of transcriptional activity from the four HBV promoters by transient-transfection analysis in the dedifferentiated hepatoma cell line, HepG2.1. It was found that the nucleocapsid and large surface antigen promoters were transactivated in the presence of HNF4 whereas the enhancer I/X gene, nucleocapsid, and large surface antigen promoters were transactivated in the presence of RXR and PPAR. Characterization of the nuclear receptors interacting with the nucleocapsid promoter region demonstrated that HNF4 is the primary transcription factor binding to the regulatory region spanning nucleotides -127 to -102 whereas HNF4, RXR-PPAR heterodimers, COUPTF1, and ARP1 bind the regulatory region spanning nucleotides -34 to -7. Transcriptional transactivation from the nucleocapsid promoter by HNF4 appears to be mediated through the two HNF4 binding sites in the promoter, whereas modulation of the level of transcription from the nucleocapsid promoter by RXR-PPAR appears to be regulated by the regulatory sequence element spanning nucleotides -34 to -7 and the HBV enhancer 1 region. These observations indicate that HBV transcription, and pregenomic RNA synthesis in particular, is regulated by ligand-dependent nuclear receptors. Agonists and antagonists capable of regulating the activity of these nuclear receptors may permit the modulation of HBV transcription and consequently replication during viral infection.