MeCP2-dependent repression of an imprinted miR-184 released by depolarization
MeCP2-dependent repression of an imprinted miR-184 released by depolarization
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DOI：
10.1093/hmg/ddn011
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发表时间：
2008-04-15
影响因子：
3.5
通讯作者：
Hatada, Izuho
中科院分区：
文献类型：
--
作者：
Nomura, Tasuku;Kimura, Mika;Hatada, Izuho
脆性X综合征和Rett综合征通常与自闭症谱系障碍有关，并涉及突触可塑性缺陷。microRNA与突触可塑性有关，因为脆性X智力低下蛋白最近与microRNA通路有关。DNA甲基化也参与突触可塑性，因为甲基CpG结合蛋白2（MeCP 2）在Rett综合征患者中发生突变。在这里，我们报告了miR-184的表达，一种被MeCP 2与其启动子结合所抑制的脑特异性microRNA，在去极化后通过释放MeCP 2而上调。MeCP 2从父本等位基因的限制性释放导致miR-184的父本等位基因特异性表达。我们的发现为microRNA和DNA甲基化途径之间的联系提供了线索。
Both fragile X syndrome and Rett syndrome are commonly associated with autism spectrum disorders and involve defects in synaptic plasticity. MicroRNA is implicated in synaptic plasticity because fragile X mental retardation protein was recently linked to the microRNA pathway. DNA methylation is also involved in synaptic plasticity since methyl CpG-binding protein 2 (MeCP2) is mutated in patients with Rett syndrome. Here we report that expression of miR-184, a brain-specific microRNA repressed by the binding of MeCP2 to its promoter, is upregulated by the release of MeCP2 after depolarization. The restricted release of MeCP2 from the paternal allele results in paternal allele-specific expression of miR-184. Our finding provides a clue to the link between the microRNA and DNA methylation pathways.