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首页> 外文期刊>Molecular cell >Destabilizing LSD1 by Jade-2 promotes neurogenesis: An antibraking system in neural development
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Destabilizing LSD1 by Jade-2 promotes neurogenesis: An antibraking system in neural development

机译：Jade-2破坏LSD1的稳定性促进神经发生：神经发育中的抗制动系统

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Histone H3K4 demethylase LSD1 plays an important role in stem cell biology, especially in the maintenance of the silencing of differentiation genes. However, how the function of LSD1 is regulated and the differentiation genes are derepressed are not understood. Here, we report that elimination of LSD1 promotes embryonic stem cell (ESC) differentiation toward neural lineage. We showed that the destabilization of LSD1 occurs posttranscriptionally via the ubiquitin-proteasome pathway by an E3 ubiquitin ligase, Jade-2. We demonstrated that Jade-2 is a major LSD1 negative regulator during neurogenesis in vitro and in vivo in both mouse developing cerebral cortices and zebra fish embryos. Apparently, Jade-2-mediated degradation of LSD1 acts as an antibraking system and serves as a quick adaptive mechanism for re-establishing epigenetic landscape without more laborious transcriptional regulations. As a potential anticancer strategy, Jade-2-mediated LSD1 degradation could potentially be used in neuroblastoma cells to induce differentiation toward postmitotic neurons.
机译：组蛋白H3K4脱甲基酶LSD1在干细胞生物学中，特别是在分化基因沉默的维持中，起着重要作用。但是，尚不了解如何调节LSD1的功能以及如何抑制分化基因。在这里，我们报告消除LSD1促进胚胎干细胞（ESC）向神经谱系分化。我们表明，LSD1的去稳定化是通过E3泛素连接酶Jade-2通过泛素-蛋白酶体途径在转录后发生的。我们证明了Jade-2是在小鼠体内发育的大脑皮层和斑马鱼胚胎的体内和体外神经发生过程中的主要LSD1负调节剂。显然，Jade-2介导的LSD1降解起着抗刹车系统的作用，并作为一种快速的适应性机制来重建表观遗传景观，而无需进行繁琐的转录调控。作为一种潜在的抗癌策略，Jade-2介导的LSD1降解可潜在地用于成神经细胞瘤细胞中，诱导向有丝分裂后神经元的分化。

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