Characterization of a Suppressive Cis-acting Element in the Epstein-Barr Virus LMP1 Promoter.
Characterization of a Suppressive Cis-acting Element in the Epstein-Barr Virus LMP1 Promoter.
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DOI：
10.3389/fmicb.2017.02302
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发表时间：
2017
影响因子：
5.2
通讯作者：
Kimura H
中科院分区：
文献类型：
--
作者：
Yoshida M;Murata T;Ashio K;Narita Y;Watanabe T;Masud HMAA;Sato Y;Goshima F;Kimura H
潜伏膜蛋白1（LMP 1）是由EB病毒（EBV）编码的主要癌基因，并且对于病毒使B细胞永生化是必需的。已有研究表明，PU.1、RBP-Jκ、NFκB、EBF 1、AP-2和STAT等转录因子参与了LMP 1的诱导，但其负调控机制尚不清楚。在此，我们将短突变引入到近端LMP 1启动子中，该启动子包括EBV-细菌人工染色体背景下的E-box和Ikaros转录因子的识别位点。感染后，突变体表现出增加的LMP 1表达和EBV介导的B细胞永生化。然而，E-box或Ikaros位点的单一突变对LMP 1表达和转化的影响有限。我们的研究结果表明，该区域包含一个抑制性顺式调节元件，但其他转录抑制因子（除了E盒和Ikaros转录因子）可能仍有待发现。
Latent membrane protein 1 (LMP1) is a major oncogene encoded by Epstein–Barr virus (EBV) and is essential for immortalization of B cells by the virus. Previous studies suggested that several transcription factors, such as PU.1, RBP-Jκ, NFκB, EBF1, AP-2 and STAT, are involved in LMP1 induction; however, the means by which the oncogene is negatively regulated remains unclear. Here, we introduced short mutations into the proximal LMP1 promoter that includes recognition sites for the E-box and Ikaros transcription factors in the context of EBV-bacterial artificial chromosome. Upon infection, the mutant exhibited increased LMP1 expression and EBV-mediated immortalization of B cells. However, single mutations of either the E-box or Ikaros sites had limited effects on LMP1 expression and transformation. Our results suggest that this region contains a suppressive cis-regulatory element, but other transcriptional repressors (apart from the E-box and Ikaros transcription factors) may remain to be discovered.
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