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首页> 外文期刊>Neuron >An essential switch in subunit composition of a chromatin remodeling complex during neural development.
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An essential switch in subunit composition of a chromatin remodeling complex during neural development.

机译：神经发育过程中染色质重塑复合物亚基组成的重要转换。

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摘要

Mammalian neural stem cells (NSCs) have the capacity to both self-renew and to generate all the neuronal and glial cell-types of the adult nervous system. Global chromatin changes accompany the transition from proliferating NSCs to committed neuronal lineages, but the mechanisms involved have been unclear. Using a proteomics approach, we show that a switch in subunit composition of neural, ATP-dependent SWI/SNF-like chromatin remodeling complexes accompanies this developmental transition. Proliferating neural stem and progenitor cells express complexes in which BAF45a, a Kruppel/PHD domain protein and the actin-related protein BAF53a are quantitatively associated with the SWI2/SNF2-like ATPases, Brg and Brm. As neural progenitors exit the cell cycle, these subunits are replaced by the homologous BAF45b, BAF45c, and BAF53b. BAF45a/53a subunits are necessary and sufficient for neural progenitor proliferation. Preventing the subunit switch impairs neuronal differentiation, indicating that this molecular event is essential for the transition from neural stem/progenitors to postmitotic neurons. More broadly, these studies suggest that SWI/SNF-like complexes in vertebrates achieve biological specificity by combinatorial assembly of their subunits.
机译：哺乳动物神经干细胞（NSC）具有自我更新和生成成人神经系统的所有神经元和神经胶质细胞类型的能力。整体染色质变化伴随着从增殖的NSC到定型神经元谱系的转变，但是涉及的机制尚不清楚。使用蛋白质组学方法，我们表明神经，ATP依赖的SWI / SNF样染色质重塑复合体的亚基组成的转换伴随着这种发展过渡。增殖性神经干细胞和祖细胞表达复合物，其中BAF45a，Kruppel / PHD域蛋白和肌动蛋白相关蛋白BAF53a与SWI2 / SNF2样ATPase，Brg和Brm定量结合。随着神经祖细胞退出细胞周期，这些亚基被同源的BAF45b，BAF45c和BAF53b取代。 BAF45a / 53a亚基是神经祖细胞增殖所必需和充分的。防止亚基转换损害神经元分化，表明该分子事件对于从神经干/祖细胞到有丝分裂后神经元的转变是必不可少的。更广泛地讲，这些研究表明脊椎动物中的SWI / SNF样复合物通过其亚基的组合组装达到生物学特异性。

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