Activation of mouse RAG-2 promoter by Myc-associated zinc finger protein.
Activation of mouse RAG-2 promoter by Myc-associated zinc finger protein.
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DOI：
10.1016/j.bbrc.2004.03.159
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发表时间：
2004-05
影响因子：
3.1
通讯作者：
Chun-xiao Wu;Wen-Pu Zhao;H. Kishi;Junichi Dokan;Zhe-xiong Jin;Xing-Cheng Wei;K. Yokoyama;A. Muraguchi
中科院分区：
文献类型：
--
作者：
Chun-xiao Wu;Wen-Pu Zhao;H. Kishi;Junichi Dokan;Zhe-xiong Jin;Xing-Cheng Wei;K. Yokoyama;A. Muraguchi
RAG-1和RAG-2在淋巴细胞发育过程中经历抗原受体基因重排的淋巴细胞中特异性表达。我们先前的研究表明，小鼠RAG-2的5′-上游区域的-41到-17个核苷酸（nt）是核心启动子活性的先决条件，并且Pax-5/c-MyB/LEF-1蛋白-蛋白复合物负责其在未成熟B细胞中的活性。在这项研究中，我们表明，−65/−42序列，人类和小鼠RAG-2启动子之间的非保守序列，是小鼠RAG-2的完整启动子活性所必需的。电泳迁移率变动分析显示，Myc相关锌指蛋白（MAZ）以及SP1/3与该区域的GA盒结合。使用染色质免疫沉淀，我们表明，MAZ结合RAG-2的启动子区在前B细胞。此外，我们表明，MAZ协同激活小鼠RAG-2启动子与Pax-5/c-Myb/LEF-1复合物。这些结果首次证明MAZ参与小鼠RAG-2启动子的激活。
Recombination activating gene-1 (RAG-1) and RAG-2 are expressed specifically in lymphocytes undergoing the antigen receptor gene rearrangement during the lymphocyte development. Our previous study showed that the −41 to −17 nucleotides (nt) 5′-upstream region of mouse RAG-2 were pre-requisite for the core promoter activity and that Pax-5/c-Myb/LEF-1 protein–protein complex was responsible for its activity in immature B cells. In this study, we show that the −65/−42 sequence, the non-conserved sequence between human and mouse RAG-2 promoter, is necessary for the full promoter activity for mouse RAG-2. Electrophoresis mobility shift assay revealed that Myc-associated zinc finger protein (MAZ) as well as SP1/3 binds a GA box in this region. Using chromatin immunoprecipitation, we show that MAZ binds the RAG-2 promoter region in pre-B cells. Furthermore, we show that MAZ synergistically activates the murine RAG-2 promoter with Pax-5/c-Myb/LEF-1 complex. These results first demonstrate that MAZ participates in activation of mouse RAG-2 promoter.