Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation.
Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation.
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DOI：
10.1016/j.stem.2010.02.017
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发表时间：
2010-05-07
期刊：
影响因子：
23.9
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Liu C;Teng ZQ;Santistevan NJ;Szulwach KE;Guo W;Jin P;Zhao X
甲基CpG结合蛋白1(MBD1)通过DNA甲基化介导的表观遗传学机制调节基因表达。我们先前已经证明，MBD1缺乏会损害成体神经干细胞分化和神经发生，但其潜在机制尚不清楚。在这里，我们发现MBD1调节着aNSCs中几个microRNAs的表达，具体地说，miR-184直接被MBD1抑制。高水平的miR-184促进了aNSCs的增殖但抑制了其分化，而抑制miR-184则挽救了与MBD1缺乏相关的表型。我们进一步发现，miR-184通过与Numblike mRNA的3‘-UTR结合并影响其翻译，调节已知的脑发育调节因子Numblike(Numblike)的表达。外源Numb1的表达可修复miR-184过表达或MBD1缺乏所致的aNSC缺陷。因此，MBD1、miR-184和Numb1形成了一个调控网络，帮助控制aNSCs的增殖和分化之间的平衡。
Methyl-CpG binding protein 1 (MBD1) regulates gene expression via a DNA methylation-mediated epigenetic mechanism. We have previously demonstrated that MBD1 deficiency impairs adult neural stem/progenitor cell (aNSC) differentiation and neurogenesis, but the underlying mechanism was unclear. Here we show that MBD1 regulates the expression of several microRNAs in aNSCs, and specifically that miR-184 is directly repressed by MBD1. High levels of miR-184 promoted proliferation but inhibited differentiation of aNSCs, whereas inhibition of miR-184 rescued the phenotypes associated with MBD1 deficiency. We further found that miR-184 regulates the expression of Numblike (Numbl), a known regulator of brain development, by binding to the 3′-UTR of Numbl mRNA and affecting its translation. Expression of exogenous Numbl could rescue the aNSC defects that result from either miR-184 overexpression or MBD1 deficiency. Therefore MBD1, miR-184, and Numbl form a regulatory network that helps control the balance between proliferation and differentiation of aNSCs.
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DOI：
10.1634/stemcells.2008-0519
发表时间：
2008-12
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Barkho BZ;Munoz AE;Li X;Li L;Cunningham LA;Zhao X
通讯作者：
Zhao X
影响因子：
1.7
作者：
Kishino, T.
通讯作者：
Kishino, T.
影响因子：
3.5
作者：
Allan, Andrea M.;Liang, Xiaomin;Zhao, Xinyu
通讯作者：
Zhao, Xinyu
影响因子：
64.5
作者：
Lewis, BP;Shih, IH;Burge, CB
通讯作者：
Burge, CB
影响因子：
9.8
作者：
John B;Enright AJ;Aravin A;Tuschl T;Sander C;Marks DS
通讯作者：
Marks DS