CPEB1, a histone-modified hypomethylated gene, is regulated by miR-101 and involved in cell senescence in glioma.
CPEB1, a histone-modified hypomethylated gene, is regulated by miR-101 and involved in cell senescence in glioma.
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CPEB1 是一种组蛋白修饰的低甲基化基因，受 miR-101 调节，参与神经胶质瘤的细胞衰老。
DOI：
10.1038/cddis.2013.197
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发表时间：
2013-06-20
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
表观遗传机制在肿瘤发生中具有重要作用。我们证实，mRNA表达相关基因胞质聚腺苷酸化元件结合蛋白1（CPEB 1）是低甲基化和过度表达的胶质瘤细胞和组织。CPEB 1的敲低通过调节胶质瘤细胞中p53的表达或分布来减少细胞衰老。CPEB 1也直接受肿瘤抑制因子miR-101（一种潜在的神经胶质瘤标志物）的调节。已知组蛋白甲基转移酶增强子zeste同源物2（EZH 2）和胚胎外胚层发育（EED）是miR-101的直接靶标。我们证明，miR-101通过调节甲基化相关组蛋白H3 K4 me 2、H3 K27 me 3、H3 K9 me 3和H4 K20 me 3的启动子上的存在，逆转CPEB 1启动子的甲基化状态，从而下调CPEB 1的表达。H3 K27 me 3对CPEB 1启动子的表观遗传调控由EZH 2和EED介导。EZH 2在H3 K4 me 2的调节中起作用。此外，CPEB 1的下调以p53依赖的方式诱导衰老。
Epigenetic mechanisms have important roles in carcinogenesis. We certified that the mRNA translation-related gene cytoplasmic polyadenylation element-binding protein 1 (CPEB1) is hypomethylated and overexpressed in glioma cells and tissues. The knockdown of CPEB1 reduced cell senescence by regulating the expression or distribution of p53 in glioma cells. CPEB1 is also regulated directly by the tumor suppressor miR-101, a potential marker of glioma. It is known that the histone methyltransferase enhancer of zeste homolog 2 (EZH2) and embryonic ectoderm development (EED) are direct targets of miR-101. We demonstrated that miR-101 downregulated the expression of CPEB1 through reversing the methylation status of the CPEB1 promoter by regulating the presence on the promoter of the methylation-related histones H3K4me2, H3K27me3, H3K9me3 and H4K20me3. The epigenetic regulation of H3K27me3 on CPEB1 promoter is mediated by EZH2 and EED. EZH2 has a role in the regulation of H3K4me2. Furthermore, the downregulation of CPEB1 induced senescence in a p53-dependent manner.
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DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
9.2
作者：
Lehnertz, B;Ueda, Y;Peters, AHFM
通讯作者：
Peters, AHFM
影响因子：
64.8
作者：
Burns, David M.;D'Ambrogio, Andrea;Nottrott, Stephanie;Richter, Joel D.
通讯作者：
Richter, Joel D.
影响因子：
3.8
作者：
Hong, Gia-Ming;Bain, Lisa J.
通讯作者：
Bain, Lisa J.
影响因子：
3.8
作者：
Hashimoto H;Vertino PM;Cheng X
通讯作者：
Cheng X