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在少突胶质细胞分化过程中,并非必需Brg1依赖性染色质重塑。

Brg1-dependent chromatin remodelling is not essentially required during oligodendroglial differentiation.

作者信息

Bischof Melanie, Weider Matthias, Küspert Melanie, Nave Klaus-Armin, Wegner Michael

机构信息

Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany, and.

Department of Neurogenetics, Max Planck Institute of Experimental Medicine, D-37075 Goettingen, Germany.

出版信息

J Neurosci. 2015 Jan 7;35(1):21-35. doi: 10.1523/JNEUROSCI.1468-14.2015.

DOI:10.1523/JNEUROSCI.1468-14.2015
PMID:25568100
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6605249/
Abstract

Myelinating Schwann cells in the vertebrate peripheral nervous system rely on Brg1 (Smarca4) for terminal differentiation. Brg1 serves as central ATP-hydrolyzing subunit of the chromatin remodelling BAF complexes and is recruited during myelination as part of these complexes by the transcription factor Sox10 in Schwann cells. Here, we analyzed the role of Brg1 during development of myelinating oligodendrocytes in the CNS of the mouse. Following Brg1 deletion in oligodendrocyte precursors, these cells showed normal survival, proliferation, and migration. A mild but significant reduction in the number of oligodendrocytes with myelin gene expression in the absence of Brg1 points to a contribution to oligodendroglial differentiation but also shows that the role of Brg1 is much less prominent than during Schwann cell differentiation. Additionally, we failed to obtain evidence for a genetic interaction between Brg1 and Sox10 comparable with the one in Schwann cells. This argues that similarities exist between the regulatory networks and mechanisms in both types of myelinating glia but that the exact mode of action and the relevance of functional interactions differ, pointing to a surprising degree of variability in the control of myelination.

摘要

脊椎动物外周神经系统中形成髓鞘的施万细胞的终末分化依赖于Brg1(Smarca4)。Brg1作为染色质重塑BAF复合物的核心ATP水解亚基,在髓鞘形成过程中,作为这些复合物的一部分,被施万细胞中的转录因子Sox10招募。在此,我们分析了Brg1在小鼠中枢神经系统中形成髓鞘的少突胶质细胞发育过程中的作用。在少突胶质细胞前体中删除Brg1后,这些细胞表现出正常的存活、增殖和迁移。在缺乏Brg1的情况下,有髓鞘基因表达的少突胶质细胞数量出现轻微但显著的减少,这表明Brg1对少突胶质细胞分化有一定作用,但也表明Brg1的作用远不如在施万细胞分化过程中那么突出。此外,我们未能获得证据证明Brg1和Sox10之间存在与施万细胞中类似的遗传相互作用。这表明在这两种形成髓鞘的神经胶质细胞的调控网络和机制之间存在相似性,但具体的作用方式和功能相互作用的相关性有所不同,这表明在髓鞘形成的控制方面存在惊人程度的变异性。

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本文引用的文献

1
Stem cell factor Sox2 and its close relative Sox3 have differentiation functions in oligodendrocytes.干细胞因子 Sox2 及其近亲 Sox3 在少突胶质细胞中具有分化功能。
Development. 2014 Jan;141(1):39-50. doi: 10.1242/dev.098418. Epub 2013 Nov 20.
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The transcription factors Sox10 and Myrf define an essential regulatory network module in differentiating oligodendrocytes.转录因子Sox10和Myrf在少突胶质细胞分化过程中定义了一个关键的调控网络模块。
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NF-κB forms a complex with the chromatin remodeler BRG1 to regulate Schwann cell differentiation.NF-κB 与染色质重塑因子 BRG1 形成复合物,调节施万细胞分化。
J Neurosci. 2013 Feb 6;33(6):2388-97. doi: 10.1523/JNEUROSCI.3223-12.2013.
5
Olig2 targets chromatin remodelers to enhancers to initiate oligodendrocyte differentiation.Olig2 将染色质重塑因子靶向增强子以启动少突胶质细胞分化。
Cell. 2013 Jan 17;152(1-2):248-61. doi: 10.1016/j.cell.2012.12.006.
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Separated at birth? The functional and molecular divergence of OLIG1 and OLIG2. 一母同胞?OLIG1 和 OLIG2 的功能和分子差异。
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7
Chromatin-remodeling factor Brg1 is required for Schwann cell differentiation and myelination.染色质重塑因子 Brg1 对于施万细胞分化和髓鞘形成是必需的。
Dev Cell. 2012 Jul 17;23(1):193-201. doi: 10.1016/j.devcel.2012.05.017.
8
The nucleosome remodeling and deacetylase chromatin remodeling (NuRD) complex is required for peripheral nerve myelination.核小体重塑和去乙酰化酶染色质重塑(NuRD)复合物对于外周神经髓鞘形成是必需的。
J Neurosci. 2012 Feb 1;32(5):1517-27. doi: 10.1523/JNEUROSCI.2895-11.2012.
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ATP-dependent chromatin remodeling: genetics, genomics and mechanisms.ATP 依赖的染色质重塑:遗传学、基因组学和机制。
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10
The closely related transcription factors Sox4 and Sox11 function as survival factors during spinal cord development.密切相关的转录因子 Sox4 和 Sox11 在脊髓发育过程中充当生存因子。
J Neurochem. 2010 Oct;115(1):131-41. doi: 10.1111/j.1471-4159.2010.06910.x. Epub 2010 Aug 3.