Suppression of Sin3A activity promotes differentiation of pluripotent cells into functional neurons.
Suppression of Sin3A activity promotes differentiation of pluripotent cells into functional neurons.
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DOI：
10.1038/srep44818
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发表时间：
2017-03-17
影响因子：
4.6
通讯作者：
Shin I
中科院分区：
文献类型：
--
作者：
Halder D;Lee CH;Hyun JY;Chang GE;Cheong E;Shin I
Sin 3是REST沉默机制的转录辅阻遏物，其抑制非神经元细胞中的多个神经元基因。然而，Sin 3（Sin 3A和Sin 3B）在抑制神经元表型中的功能还没有得到很好的表征。在此，我们表明，Sin 3A敲低阻碍了REST的抑制活性，并增强了多能P19细胞分化成电生理活性神经元，而不诱导星形细胞。还发现沉默Sin 3B诱导P19细胞的神经发生的效率低于Sin 3A敲低。结果表明，Sin 3A对P19细胞中用于沉默神经元基因的REST阻遏机制具有比Sin 3B更深刻的影响。此外，我们表明，Sin 3A-REST相互作用的肽抑制剂促进P19细胞分化为功能性神经元。在使用基因缺失和合成抑制剂的研究中所做的观察表明，Sin 3A在REST调节机制对神经元基因的抑制中起着重要作用。
Sin3 is a transcriptional corepressor for REST silencing machinery that represses multiple neuronal genes in non-neuronal cells. However, functions of Sin3 (Sin3A and Sin3B) in suppression of neuronal phenotypes are not well characterized. Herein we show that Sin3A knockdown impedes the repressive activity of REST and enhances differentiation of pluripotent P19 cells into electrophysiologically active neurons without inducing astrogenesis. It is also found that silencing Sin3B induces neurogenesis of P19 cells with a lower efficiency than Sin3A knockdown. The results suggest that Sin3A has a more profound effect on REST repressive machinery for silencing neuronal genes in P19 cells than Sin3B. Furthermore, we show that a peptide inhibitor of Sin3A-REST interactions promotes differentiation of P19 cells into functional neurons. Observations made in studies using genetic deletion and a synthetic inhibitor suggests that Sin3A plays an important role in the repression of neuronal genes by the REST regulatory mechanism.