A Novel Function of TET2 in CNS: Sustaining Neuronal Survival.
A Novel Function of TET2 in CNS: Sustaining Neuronal Survival.
复制标题
TET2 在中枢神经系统中的新功能：维持神经元存活
DOI：
10.3390/ijms160921846
复制
发表时间：
2015-09-10
影响因子：
5.6
通讯作者：
Jin W
中科院分区：
文献类型：
--
作者：
Mi Y;Gao X;Dai J;Ma Y;Xu L;Jin W
DNA双加氧酶Ten-Eleven易位(Tet)蛋白可以催化DNA的5-甲基胞嘧啶(5mC)转化为5-羟甲基胞嘧啶(5hmC)，从而改变DNA的表观遗传状态。Tet家族包括哺乳动物中的TET1、TET2和TET3成员。近年来，大量研究发现，TET1-3在中枢神经系统(CNS)中大量存在，其生物学功能的研究才刚刚开始。在本研究中，我们证明了TET2的mRNA和蛋白在大脑发育的整个过程中在大脑皮层和海马区都有高表达。进一步的研究表明，TET2在各种类型的细胞中都有表达，尤其是在大多数神经元中。亚细胞分布模式提示TET2定位于神经元的胞核和胞浆。用RNA干扰下调培养的皮层神经元中TET2的表达，表明TET2是细胞生存所必需的。总之，我们的结果表明神经元TET2正向参与细胞存活的调节。
DNA dioxygenases Ten-Eleven Translocation (TET) proteins can catalyze the conversion of 5-methylcytosine (5mC) of DNA to 5-hydroxymethylcytosine (5hmC), and thereby alter the epigenetic state of DNA. The TET family includes TET1, TET2 and TET3 members in mammals. Recently, accumulative research uncovered that TET1–3 occur abundantly in the central nervous system (CNS), and their biological functions have just begun to be investigated. In the present study, we demonstrated that mRNA and protein of TET2 were highly expressed in the cerebral cortex and hippocampus along the whole brain-development process. Further studies showed that TET2 was expressed in various types of cells, especially in most neurons. Subcellular distribution pattern implicated that TET2 is localized in both nucleus and cytoplasm of neurons. Down-regulation of TET2 in cultured cortical neurons with RNA interference implied that TET2 was required for cell survival. In all, our results indicate that neuronal TET2 is positively involved in the regulation of cell survival.