Cross talk between microRNA and epigenetic regulation in adult neurogenesis.
Cross talk between microRNA and epigenetic regulation in adult neurogenesis.
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DOI：
10.1083/jcb.200908151
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发表时间：
2010-04-05
期刊：
影响因子：
--
通讯作者：
Jin P
中科院分区：
文献类型：
--
作者：
Szulwach KE;Li X;Smrt RD;Li Y;Luo Y;Lin L;Santistevan NJ;Li W;Zhao X;Jin P
microRNA miR-137抑制Ezh 2（一种组蛋白甲基转移酶）的表达，这反过来改变了染色质的表观遗传结构，这对miR-137水平的调节很重要。microRNA（miRNAs）和表观遗传调控在干细胞生物学中具有重要的功能，尽管这两种途径之间的相互作用还不清楚。在这里，我们表明，MeCP 2，DNA甲基-CpG结合蛋白，可以表观遗传调节特定的miRNA在成体神经干细胞（aNSCs）。MeCP 2介导的一种这样的miRNA，miR-137的表观遗传调控涉及Sox 2的共调控，Sox 2是干细胞中的核心转录因子。miR-137在体外和体内调节aNSC的增殖和分化。miR-137的过表达促进aNSC的增殖，而miR-137的减少增强aNSC的分化。我们进一步表明，miR-137转录后抑制Ezh 2，组蛋白甲基转移酶和Polycomb组（PcG）蛋白的表达。miR-137介导的Ezh 2抑制反馈到染色质，导致组蛋白H3三甲基赖氨酸27的整体减少。Ezh 2的共表达可以挽救与miR-137过表达相关的表型。这些结果表明，miRNA和表观遗传调控之间的串扰有助于成年神经发生的调节。
The microRNA miR-137 represses expression of Ezh2, a histone methyltransferase, which in turn alters the epigenetic architecture of chromatin that is important for regulation of miR-137 levels. Both microRNAs (miRNAs) and epigenetic regulation have important functions in stem cell biology, although the interactions between these two pathways are not well understood. Here, we show that MeCP2, a DNA methyl-CpG–binding protein, can epigenetically regulate specific miRNAs in adult neural stem cells (aNSCs). MeCP2-mediated epigenetic regulation of one such miRNA, miR-137, involves coregulation by Sox2, a core transcription factor in stem cells. miR-137 modulates the proliferation and differentiation of aNSCs in vitro and in vivo. Overexpression of miR-137 promotes the proliferation of aNSCs, whereas a reduction of miR-137 enhances aNSC differentiation. We further show that miR-137 post-transcriptionally represses the expression of Ezh2, a histone methyltransferase and Polycomb group (PcG) protein. The miR-137–mediated repression of Ezh2 feeds back to chromatin, resulting in a global decrease in histone H3 trimethyl lysine 27. Coexpression of Ezh2 can rescue phenotypes associated with miR-137 overexpression. These results demonstrate that cross talk between miRNA and epigenetic regulation contributes to the modulation of adult neurogenesis.
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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
25
作者：
Ballas, Nurit;Lioy, Daniel T.;Grunseich, Christopher;Mandel, Gail
通讯作者：
Mandel, Gail
DOI：
10.1196/annals.1392.008
发表时间：
2007-01-01
期刊：
HEMATOPOIETIC STEM CELLS VI
影响因子：
--
作者：
de Haan, Gerald;Gerrits, Alice
通讯作者：
Gerrits, Alice
影响因子：
10.5
作者：
Avilion, AA;Nicolis, SK;Lovell-Badge, R
通讯作者：
Lovell-Badge, R
影响因子：
30.8
作者：
Coffee, B;Zhang, FP;Reines, D
通讯作者：
Reines, D