Combinatorial action of miRNAs regulates transcriptional and post-transcriptional gene silencing following in vivo PNS injury.
Combinatorial action of miRNAs regulates transcriptional and post-transcriptional gene silencing following in vivo PNS injury.
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DOI：
10.1371/journal.pone.0039674
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Tapinos N
中科院分区：
文献类型：
--
作者：
Adilakshmi T;Sudol I;Tapinos N
周围神经系统(PNS)的损伤反应以雪旺细胞遗传程序的快速改变为特征。然而，调控这些变化的表观遗传机制仍然难以捉摸。在这里，我们展示了小鼠坐骨神经损伤诱导了22个miRNAs的队列，这些miRNAs通过它们的正负基因调节因子的组合调节来协调雪旺细胞的分化和去分化。这些miRNAs及其靶向mRNAs与ArgAerte-2蛋白形成功能复合体，介导转录后基因沉默。在队列中，MIR-138和miR-709对Egr2、Sox-2和c-jun表达的结合和调节显示出最高的亲和力。此外，miR-709还参与与H3K27me3和ArgAerte-1形成表观遗传沉默复合体，诱导Egr2启动子的转录基因沉默。总的来说，我们确定了一个离散的miRNAs队列，作为PNS损伤急性期分化和去分化之间转换的中心表观遗传调节因子。
Injury response in the peripheral nervous system (PNS) is characterized by rapid alterations in the genetic program of Schwann cells. However, the epigenetic mechanisms modulating these changes remain elusive. Here we show that sciatic nerve injury in mice induces a cohort of 22 miRNAs, which coordinate Schwann cell differentiation and dedifferentiation through a combinatorial modulation of their positive and negative gene regulators. These miRNAs and their targeted mRNAs form functional complexes with the Argonaute-2 protein to mediate post-transcriptional gene silencing. MiR-138 and miR-709 show the highest affinity amongst the cohort, for binding and regulation of Egr2, Sox-2 and c-Jun expression following injury. Moreover, miR-709 participates in the formation of epigenetic silencing complexes with H3K27me3 and Argonaute-1 to induce transcriptional gene silencing of the Egr2 promoter. Collectively, we identified a discrete cohort of miRNAs as the central epigenetic regulators of the transition between differentiation and dedifferentiation during the acute phase of PNS injury.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
DOI：
10.1073/pnas.0808830105
发表时间：
2008-10-21
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
16.8
作者：
Long, Dang;Lee, Rosalind;Ding, Ye
通讯作者：
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影响因子：
3.7
作者：
Bremer J;O'Connor T;Tiberi C;Rehrauer H;Weis J;Aguzzi A
通讯作者：
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