Dynamics of Tet hydroxylase family proteins and 5-hydroxymethylcytosine in oligodendrocyte differentiation
Dynamics of Tet hydroxylase family proteins and 5-hydroxymethylcytosine in oligodendrocyte differentiation
复制标题
Tet羟化酶家族蛋白和5-羟甲基胞嘧啶在少突胶质细胞分化中的动态
作者：
Zhao Xianghui;Dai Jinxiang;Ma Yue;Mi Yajing;Cui Daxiang;Ju Gong;Macklin Wendy B.;Jin Weilin
甲基胞嘧啶双加氧酶的10 - 11易位（泰特）家族催化5-甲基胞嘧啶（5 mC）氧化为5-羟甲基胞嘧啶（5 hmC）并促进DNA去甲基化。尽管5 hmC和泰特蛋白在脑中丰富，但对它们在少突胶质细胞（OLs）中的作用知之甚少。在此，我们分析了泰特在体内和体外OL发育过程中的表达，发现三个泰特家族成员具有独特的亚细胞和时间表达模式。此外，5 hmC的水平在OL成熟过程中呈现动态变化，这意味着5 hmC修饰可能在OL成熟所需的关键基因的表达中起作用。OL中泰特家族蛋白的siRNA介导的沉默证明了OL分化需要每种泰特蛋白。然而，基于它们独特的结构域，我们推测这三个泰特成员可能通过不同的机制发挥作用。总之，我们已经建立了泰特蛋白的时间表达和OL发育过程中5 hmC的动态水平，并证明所有三个泰特成员是OL分化所必需的。GLIA 2014;62：914-926
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 developmentin vivoandin 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. GLIA 2014;62:914–926