Identification of a negative cis element within the ZII domain of the Epstein-Barr virus lytic switch BZLF1 gene promoter
Identification of a negative cis element within the ZII domain of the Epstein-Barr virus lytic switch BZLF1 gene promoter
复制标题
DOI：
10.1128/jvi.72.10.8230-8239.1998
复制
发表时间：
1998-10-01
影响因子：
5.4
通讯作者：
Speck, SH
中科院分区：
文献类型：
--
作者：
Liu, PF;Liu, SF;Speck, SH
Epstein-Barr 病毒 (EBV) 裂解开关基因 BZLF1 在潜伏感染的 B 细胞中受到严格调控。 BZLF1 基因启动子 (Zp) 包含多个顺式元件，先前已证明这些元件可响应病毒裂解周期的诱导剂。其中包括被称为 ZI 结构域的元件的四个副本和包含共有 CRE/AP-1 基序（ZII 结构域）的元件。此外，Zp 通过两个结合 BZLF1 基因产物 Zta 的位点进行自动调节。 ZI结构域已显示结合普遍存在的细胞转录因子Spl和Sp3和/或肌细胞增强因子2D(Liu等人，EMBO J. 16：143-153，1997；Liu等人，Virology 228：9-16，1997)。在这里，我们对 ZII 结构域进行了功能分析，结果表明：(i) ATF-1 和 ATF3 似乎是与 ZII 结构域中存在的 CRE/AP-1 基序结合的主要细胞因子； (ii) CRE/AP-1 基序紧邻上游的区域含有强效负顺式元件，其突变导致 Zp 活性增加 > 10 倍。 ZII 结构域中的负顺式元件 (ZIIR) 会降低基础 Zp 活性和诱导 Zp 活性，因此可能在调节 EBV 重新激活中发挥重要作用。此外，异源启动子构建体的分析表明 ZIIR 的功能是上下文敏感的。证明细胞因子与 ZIIR 结合的尝试并未成功，从而导致介导抑制的机制尚未解决。
The Epstein-Barr virus (EBV) lytic switch gene, BZLF1, is tightly regulated in latently infected B cells. The BZLF1 gene promoter (Zp) contains several cis elements that have been previously shown to respond to inducers of the viral lytic cycle. These include four copies of an element referred to as the ZI domains and an element that contains a consensus CRE/AP-1 motif (ZII domain). In addition, Zp is autoregulated through two sites that bind the BZLF1 gene product Zta. The ZI domains have been shown to bind the ubiquitous cellular transcription factors Spl and Sp3 and/or the myocyte enhancer factor 2D (Liu et al., EMBO J. 16:143-153, 1997; Liu et al., Virology 228:9-16, 1997). Here we present a functional analysis of the ZII domain and show: (i) ATF-1 and ATF3 appear to be the predominant cellular factors that bind to the CRE/AP-1 motif present in the ZII domain; and (ii) the region immediately upstream of the CRE/AP-1 motif contains a potent negative cis element, mutation of which results in a > 10-fold increase in Zp activity. The negative cis element (ZIIR) in the ZII domain decreases both basal and induced Zp activity and thus is likely to play an important role in regulating reactivation of EBV. In addition, analysis of heterologous promoter constructs indicates that the function of ZIIR is context sensitive. Attempts to demonstrate a cellular factor binding to ZIIR have been unsuccessful, leaving unresolved the mechanism by which repression is mediated.