抑制 Sin3A 活性可促进多能干细胞向功能性神经元分化。
Suppression of Sin3A activity promotes differentiation of pluripotent cells into functional neurons.
机构信息
National Creative Research Initiative Center for Biofunctional Molecules, Department of Chemistry, Yonsei University, Seoul 03722, Korea.
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
出版信息
Sci Rep. 2017 Mar 17;7:44818. doi: 10.1038/srep44818.
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.
Sin3 是 REST 沉默机制的转录共抑制因子，可在非神经元细胞中抑制多种神经元基因。然而，Sin3（Sin3A 和 Sin3B）在抑制神经元表型方面的功能尚未得到很好的表征。在此，我们发现 Sin3A 敲低会阻碍 REST 的抑制活性，并增强多能 P19 细胞向具有电生理活性神经元的分化，而不会诱导星形胶质细胞发生。还发现，与 Sin3A 敲低相比，沉默 Sin3B 诱导 P19 细胞神经发生的效率较低。结果表明，与 Sin3B 相比，Sin3A 对 P19 细胞中 REST 抑制神经元基因的抑制机制具有更深远的影响。此外，我们还表明，Sin3A-REST 相互作用的肽抑制剂可促进 P19 细胞向功能性神经元分化。使用基因缺失和合成抑制剂进行的研究观察表明，Sin3A 在 REST 调节机制对神经元基因的抑制中发挥重要作用。
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