Chromatin modification of Notch targets in olfactory receptor neuron diversification
Chromatin modification of Notch targets in olfactory receptor neuron diversification
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DOI：
10.1038/nn.2998
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发表时间：
2012-02-01
影响因子：
25
通讯作者：
Moore, Adrian W.
中科院分区：
文献类型：
--
作者：
Endo, Keita;Karim, M. Rezaul;Moore, Adrian W.
神经元类的多样化是神经发生的中心。这种要求在嗅觉系统中得到了体现，嗅觉系统利用了大量的嗅觉受体神经元（ORN）类。我们发现了一种表观遗传机制，其中神经元多样性通过基因座特异性染色质修饰最大化，该修饰从单个通常使用的细胞内信号产生上下文依赖性反应。果蝇中的每个ORN获得三个基本身份之一，这三个基本身份是由神经发生过程中三个重复的Notch信号事件的复合结果定义的。哈姆雷特，果蝇邪恶和Prdm 16原癌基因同源物，修改这些迭代使用的Notch信号的细胞反应，在上下文依赖的方式，并控制气味受体基因的选择和ORN轴突靶向特异性。在新生的ORN中，哈姆雷特消除了从亲本细胞继承的Notch状态，从而在随后一轮的Notch信号传导中实现了修饰的反应。哈姆雷特指导组蛋白甲基化和组蛋白密度的基因座特异性修饰，并控制Notch靶启动子处DNA结合蛋白无毛抑制因子的可及性。
Neuronal-class diversification is central during neurogenesis. This requirement is exemplified in the olfactory system, which utilizes a large array of olfactory receptor neuron (ORN) classes. We discovered an epigenetic mechanism in which neuron diversity is maximized via locus-specific chromatin modifications that generate context-dependent responses from a single, generally used intracellular signal. Each ORN in Drosophila acquires one of three basic identities defined by the compound outcome of three iterated Notch signaling events during neurogenesis. Hamlet, the Drosophila Evil and Prdm16 proto-oncogene homolog, modifies cellular responses to these iteratively used Notch signals in a context-dependent manner, and controls odorant receptor gene choice and ORN axon targeting specificity. In nascent ORNs, Hamlet erases the Notch state inherited from the parental cell, enabling a modified response in a subsequent round of Notch signaling. Hamlet directs locus-specific modifications of histone methylation and histone density and controls accessibility of the DNA-binding protein Suppressor of Hairless at the Notch target promoter.