Type II Arginine Methyltransferase PRMT5 Regulates Gene Expression of Inhibitors of Differentiation/DNA Binding Id2 and Id4 during Glial Cell Differentiation
Type II Arginine Methyltransferase PRMT5 Regulates Gene Expression of Inhibitors of Differentiation/DNA Binding Id2 and Id4 during Glial Cell Differentiation
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DOI：
10.1074/jbc.m111.277046
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发表时间：
2011-12-30
影响因子：
4.8
通讯作者：
Richard, Stephane
中科院分区：
文献类型：
--
作者：
Huang, Jinghan;Vogel, Gillian;Richard, Stephane
PRMT5 是一种 II 型蛋白精氨酸甲基转移酶，可催化精氨酸残基的单甲基化和对称二甲基化。 PRMT5 在功能上参与多种生物过程，包括胚胎发育和生物钟调节。然而，PRMT5 在少突胶质细胞分化和中枢神经系统髓鞘形成中的作用尚不清楚。在这里，我们发现 PRMT5 表达在整个出生后大脑发育过程中逐渐增加，与活跃的髓鞘形成时期一致。在神经元、星形胶质细胞和少突胶质细胞中观察到 PRMT5 表达。 siRNA介导的小鼠原代少突胶质细胞祖细胞中PRMT5的缺失消除了少突胶质细胞的分化。此外，PRMT5耗尽的少突胶质细胞祖细胞和C6神经胶质瘤细胞表达高水平的分化/DNA结合抑制剂Id2和Id4，这是已知的神经胶质细胞分化抑制剂。我们观察到，Id2 和 Id4 基因内富含 CpG 的岛与 PRMT5 结合，并且在 PRMT5 缺陷细胞中低甲基化，表明 PRMT5 在神经胶质细胞分化过程中的基因沉默中发挥作用。我们的研究结果定义了 PRMT5 在神经胶质细胞分化中的作用，并将 PRMT5 与少突胶质细胞分化过程中的表观遗传变化联系起来。
PRMT5 is a type II protein arginine methyltranferase that catalyzes monomethylation and symmetric dimethylation of arginine residues. PRMT5 is functionally involved in a variety of biological processes including embryo development and circadian clock regulation. However, the role of PRMT5 in oligodendrocyte differentiation and central nervous system myelination is unknown. Here we show that PRMT5 expression gradually increases throughout postnatal brain development, coinciding with the period of active myelination. PRMT5 expression was observed in neurons, astrocytes, and oligodendrocytes. siRNA-mediated depletion of PRMT5 in mouse primary oligodendrocyte progenitor cells abrogated oligodendrocyte differentiation. In addition, the PRMT5-depleted oligodendrocyte progenitor and C6 glioma cells expressed high levels of the inhibitors of differentiation/DNA binding, Id2 and Id4, known repressors of glial cell differentiation. We observed that CpG-rich islands within the Id2 and Id4 genes were bound by PRMT5 and were hypomethylated in PRMT5-deficient cells, suggesting that PRMT5 plays a role in gene silencing during glial cell differentiation. Our findings define a role of PRMT5 in glial cell differentiation and link PRMT5 to epigenetic changes during oligodendrocyte differentiation.