Dynamics of RNA Polymerase II Pausing and Bivalent Histone H3 Methylation during Neuronal Differentiation in Brain Development.

Dynamics of RNA Polymerase II Pausing and Bivalent Histone H3 Methylation during Neuronal Differentiation in Brain Development.
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大脑发育神经元分化过程中 RNA 聚合酶 II 暂停和二价组蛋白 H3 甲基化的动态。

DOI:
10.1016/j.celrep.2017.07.046
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发表时间:
2017-08-08
期刊:
影响因子:
8.8
通讯作者:
Lu Q
Lu Q
中科院分区:
生物学1区
文献类型:
--
作者:
Liu J;Wu X;Zhang H;Pfeifer GP;Lu Q

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在细胞分化过程中,预期对分化重要的基因在干细胞/祖细胞中是沉默的,但可以容易地被激活。RNA聚合酶II(Pol II)暂停和二价染色质标记是两个范例适合建立这样一个平衡的基因表达状态,然而,他们在发展中的具体贡献还没有得到很好的理解。在这里,我们的特点Pol II暂停和H3 K4 me 3/H3 K27 me 3标记的神经祖细胞(NPC)和他们的女儿神经元纯化从发展中的小鼠皮层。我们发现,暂停在NPC或神经元的基因是各自的细胞功能的特点,重要的每种细胞类型,虽然暂停和暂停释放与基因激活不相关。二价染色质标记使NPC中标记的基因在神经元中活化。有趣的是,我们观察到H3 K27 me 3和暂停的Pol II之间的正相关性。因此,这项研究揭示了细胞类型特异性Pol II暂停和基因激活相关的二价在哺乳动物神经元分化。
During cellular differentiation, genes important for differentiation are expected to be silent in stem/progenitor cells yet can be readily activated. RNA polymerase II (Pol II) pausing and bivalent chromatin marks are two paradigms suited for establishing such a poised state of gene expression, however, their specific contributions in development are not well understood. Here, we characterized Pol II pausing and H3K4me3/H3K27me3 marks in neural progenitor cells (NPCs) and their daughter neurons purified from the developing mouse cortex. We show that genes paused in NPCs or neurons are characteristic of respective cellular functions important for each cell type, although pausing and pause release was not correlated with gene activation. Bivalent chromatin marks poised the marked genes in NPCs for activation in neurons. Interestingly, we observed a positive correlation between H3K27me3 and paused Pol II. This study thus reveals cell-type specific Pol II pausing and gene activation-associated bivalency during mammalian neuronal differentiation.
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