Jmjd2c histone demethylase enhances the expression of Mdm2 oncogene
Jmjd2c histone demethylase enhances the expression of Mdm2 oncogene
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DOI：
10.1016/j.bbrc.2009.08.155
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发表时间：
2009-11-13
影响因子：
3.1
通讯作者：
Suzuki, Takeshi
中科院分区：
文献类型：
--
作者：
Ishimura, Akihiko;Terashima, Minoru;Suzuki, Takeshi
Jmjd2c是编码组蛋白赖氨酸去甲基化酶的候选癌基因。在本研究中，我们发现Jmjd2c的过表达依赖于其脱甲基酶活性而增加了Mdm 2癌基因的表达，从而导致细胞中p53抑癌基因产物的减少。染色质免疫沉淀试验表明，Jmjd2c被募集到Mdm 2基因的P2启动子区，导致组蛋白H3赖氨酸9的去甲基化，这通常在活跃转录的基因中发现。此外，siRNA介导的Jmjd2c敲低导致细胞中Mdm2表达减少。这些结果表明，Mdm 2癌基因是Jmjd2c的下游靶点，可能在Jmjd2c介导的肿瘤发生中起重要作用。(C)2009 Elsevier Inc. All rights reserved.
Jmjd2c is a candidate oncogene that encodes histone lysine demethylase. In this study, we discovered that over-expression of Jmjd2c increased the expression of Mdm2 oncogene dependent on its demethylase activity, which led to the reduction of p53 tumor suppressor gene product in the cells. A chromatin immunoprecipitation assay showed that Jmjd2c was recruited to the P2 promoter region of Mdm2 gene resulting in demethylation of histone H3 lysine 9, as typically found in actively transcribed genes. Furthermore, siRNA-mediated knockdown of Jmjd2c caused the reduction of Mdm2 expression in the cells. These results indicate that Mdm2 oncogene is a downstream target of Jmjd2c and may play an important role in Jmjd2c-mediated oncogenesis. (C) 2009 Elsevier Inc. All rights reserved.