KDM3A-mediated demethylation of histone H3 lysine 9 facilitates the chromatin binding of Neurog2 during neurogenesis
KDM3A-mediated demethylation of histone H3 lysine 9 facilitates the chromatin binding of Neurog2 during neurogenesis
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KDM3A 介导的组蛋白 H3 赖氨酸 9 去甲基化促进神经发生过程中 Neurog2 的染色质结合
DOI：
10.1242/dev.144113
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发表时间：
2017-10-15
期刊：
影响因子：
4.6
通讯作者：
Tao, Qinghua
中科院分区：
文献类型：
--
作者：
Lin, Hao;Zhu, Xuechen;Tao, Qinghua
Neurog2是体内和体外神经元命运指定和分化的重要调节因子。然而，目前尚不清楚Neurog2如何反式激活被抑制性染色质沉默的神经元基因。在这里，我们提供了组蛋白H3赖氨酸9去甲基酶KDM3A促进非洲爪哇神经2(以前称为Xngnr1)染色质在神经元转录过程中的可及性的证据。功能丧失分析表明，KDM3A不是幼稚外胚层向神经前体细胞转化所必需的，而是初级神经元形成所必需的。芯片序列和qPCR分析表明，Neurog2促进了抑制的H3K9me2标记的去除，并在Neurod1和Tubb2b启动子上增加了活性的组蛋白标记，包括H3K27ac和H3K4me3；这一活性取决于KDM3A的存在，因为Neurog2通过其C-末端结构域与KDM3A相互作用。有趣的是，KDM3A对于Ascl1启动的神经元转录是必不可少的，Ascl1是一种与bHLH家族中的神经原蛋白相关的前神经因子。综上所述，我们的发现揭示了组蛋白H3K9去甲基化在Neurog2介导的神经元转录中的关键作用，并有助于理解Neurog2和Ascl1在启动神经元发育中的不同活动。摘要：H3K9去甲基酶KDM3A在非洲爪哇神经转录过程中增强了Neurog2的染色质结合，但不是Ascl1诱导神经元基因表达所必需的。
Neurog2 is a crucial regulator of neuronal fate specification and differentiation in vivo and in vitro. However, it remains unclear how Neurog2 transactivates neuronal genes that are silenced by repressive chromatin. Here, we provide evidence that the histone H3 lysine 9 demethylase KDM3A facilitates the Xenopus Neurog2 (formerly known as Xngnr1) chromatin accessibility during neuronal transcription. Loss-of-function analyses reveal that KDM3A is not required for the transition of naive ectoderm to neural progenitor cells but is essential for primary neuron formation. ChIP series followed by qPCR analyses reveal that Neurog2 promotes the removal of the repressive H3K9me2 marks and addition of active histone marks, including H3K27ac and H3K4me3, at the NeuroD1 and Tubb2b promoters; this activity depends on the presence of KDM3A because Neurog2, via its C-terminal domain, interacts with KDM3A. Interestingly, KDM3A is dispensable for the neuronal transcription initiated by Ascl1, a proneural factor related to neurogenin in the bHLH family. In summary, our findings uncover a crucial role for histone H3K9 demethylation during Neurog2-mediated neuronal transcription and help in the understanding of the different activities of Neurog2 and Ascl1 in initiating neuronal development. Summary: The H3K9 demethylase KDM3A enhances the chromatin binding of Neurog2 during neuronal transcription in Xenopus but is not required for Ascl1 to induce neuronal gene expression.