Activation of Sp1-mediated transcription by Rta of Epstein-Barr virus via an interaction with MCAF1.

Activation of Sp1-mediated transcription by Rta of Epstein-Barr virus via an interaction with MCAF1.
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DOI:
10.1093/nar/gki956
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发表时间:
2005
影响因子:
14.9
通讯作者:
Liu ST
Liu ST
中科院分区:
生物学2区
文献类型:
--
作者:
Chang LK;Chung JY;Hong YR;Ichimura T;Nakao M;Liu ST

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Rta是由EB病毒(EBV)的BRLF 1编码的转录因子。该因子在裂解周期的早期阶段表达,以激活EBV裂解发育所需的基因。尽管Rta的转录激活通常与Rta与启动子中的Rta响应元件(RRE)的结合有关,但Rta有时激活没有RRE的启动子。在这里,我们表明,Rta与Sp1相互作用的蛋白,MBD 1含有染色质相关因子1(MCAF 1)。这种相互作用对于在Sp1位点形成Sp1-MCAF 1-Rta复合物至关重要。因此,在裂解诱导和Rta的表达之后,Rta增加了Sp1介导的转录。因此被激活的基因包括p16、p21、SNRPN和BRLF 1。然而,Rta与RRE的结合阻止了Rta和MCAF 1之间的相互作用;因此,RRE的转录激活仅依赖于Rta,而不依赖于MCAF 1或Sp1。此外,本研究还发现MCAF 1可促进EBV Rta和Zta的表达,提示MCAF 1参与了EBV的裂解激活。我们的研究记录了Rta在调节Sp1介导的基因转录中的关键作用。
Rta is a transcription factor encoded by BRLF1 of the Epstein–Barr virus (EBV). This factor is expressed during the immediate-early stage of the lytic cycle to activate the genes required for EBV lytic development. Although transcription activation by Rta is frequently associated with the binding of Rta to the Rta-response element (RRE) in promoters, Rta sometimes activates promoters without an RRE. Here we show that Rta interacts with an Sp1-interacting protein, MBD1-containing chromatin-associated factor 1 (MCAF1). This interaction is critical to the formation of an Sp1–MCAF1–Rta complex at Sp1 sites. Therefore, following lytic induction and the expression of Rta, Rta increases Sp1-mediated transcription. The genes that are thus activated include p16, p21, SNRPN and BRLF1. However, the binding of Rta to RRE prevents the interaction between Rta and MCAF1; therefore, transcription activation by RRE depends only on Rta, and not on MCAF1 or Sp1. Furthermore, this study finds that MCAF1 promotes the expression of Rta and Zta from EBV, indicating that MCAF1 participates EBV lytic activation. Our study documents the critical role of Rta in regulating the transcription of the genes that are mediated by Sp1.
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发表时间: 2004-09-10
影响因子: 4.8
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