The Epstein-Barr virus transactivator Zta binds to its own promoter and is required for full promoter activity during anti-Ig and TGF-beta1 mediated reactivation.

The Epstein-Barr virus transactivator Zta binds to its own promoter and is required for full promoter activity during anti-Ig and TGF-beta1 mediated reactivation.
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Epstein-Barr 病毒反式激活子 Zta 与其自身的启动子结合,并且是抗 Ig 和 TGF-β1 介导的重新激活过程中启动子完全活性所必需的。

DOI:
10.1016/j.virol.2004.06.026
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发表时间:
2004
期刊:
Virology.
影响因子:
--
通讯作者:
Flemington,ErikK
Flemington,ErikK
中科院分区:
--
文献类型:
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作者:
Yin,Qinyan;Jupiter,Kendra;Flemington,ErikK

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即刻早期基因BZLF1的转录最初是通过激活细胞转录因子来调节的。基于报道的研究已经提供了证据表明,在这种初始激活之后,BZLF1基因产物Zta可能通过与其启动子ZP结合而参与到自激活循环中。相反,其他报告显示,在潜伏感染细胞中转染Zta表达载体并不能激活内源性ZP。利用染色质免疫沉淀(ChIP)分析,我们发现Zta在抗-Ig和转化生长因子-β1诱导的裂解循环后与内源性ZP结合,并且结合发生得足够早,在ZP的激活中发挥作用。我们还产生了显性-负性Zta,并表明它抑制内源ZP的激活。这些数据支持ZP在重新激活过程中的两步激活模型,该模型包括由细胞因子初始激活,然后是自动激活步骤。
Transcription of the immediate early gene BZLF1 is mediated initially through the activation of cellular transcription factors. Reporter-based studies have provided evidence that following this initial activation, the BZLF1 gene product Zta may be involved in an autoactivation loop through binding to its promoter Zp. In contrast, other reports have shown that transfection of a Zta expression vector in latently infected cells does not activate endogenous Zp. Using chromatin immunoprecipitation (ChIP) assays, we show here that Zta binds to endogenous Zp following induction of the lytic cycle by anti-Ig and TGF-beta1 and that binding occurs early enough to play a role in the activation of Zp. We have also generated a dominant-negative Zta and shown that it inhibits activation of endogenous Zp. These data support a two-step model for Zp activation during reactivation involving initial activation by cellular factors followed by an autoactivation step.