Zhao Xianghui, Dai Jinxiang, Ma Yue, Mi Yajing, Cui Daxiang, Ju Gong, Macklin Wendy B, Jin Weilin
Institute of Neuroscience, Fourth Military Medical University, Xi'an, China.
Glia. 2014 Jun;62(6):914-26. doi: 10.1002/glia.22649. Epub 2014 Feb 25.
The ten-eleven translocation (TET) family of methylcytosine dioxygenases catalyze oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and promote DNA demethylation. Despite the abundance of 5hmC and TET proteins in the brain, little is known about their role in oligodendrocytes (OLs). Here, we analyzed TET expression during OL development in vivo and in vitro, and found that three TET family members possess unique subcellular and temporal expression patterns. Furthermore, the level of 5hmC exhibits dynamic changes during OL maturation, which implies that 5hmC modification may play a role in the expression of critical genes necessary for OL maturation. siRNA-mediated silencing of the TET family proteins in OLs demonstrated that each of the TET proteins is required for OL differentiation. However, based on their unique domain structures, we speculate that the three TET members may function by different mechanisms. In summary, we have established the temporal expression of TET proteins and the dynamic level of 5hmC during OL development and demonstrate that all three TET members are necessary for OL differentiation.
甲基胞嘧啶双加氧酶的十 - 十一易位（TET）家族催化5 - 甲基胞嘧啶（5mC）氧化为5 - 羟甲基胞嘧啶（5hmC），并促进DNA去甲基化。尽管大脑中5hmC和TET蛋白含量丰富，但它们在少突胶质细胞（OLs）中的作用却鲜为人知。在此，我们分析了体内和体外OL发育过程中TET的表达情况，发现TET家族的三个成员具有独特的亚细胞和时间表达模式。此外，5hmC水平在OL成熟过程中呈现动态变化，这意味着5hmC修饰可能在OL成熟所需关键基因的表达中发挥作用。在OL中通过小干扰RNA（siRNA）介导沉默TET家族蛋白表明，每个TET蛋白都是OL分化所必需的。然而，基于它们独特的结构域结构，我们推测这三个TET成员可能通过不同机制发挥作用。总之，我们确定了OL发育过程中TET蛋白的时间表达以及5hmC的动态水平，并证明所有三个TET成员都是OL分化所必需的。
