A Functional Switch of NuRD Chromatin Remodeling Complex Subunits Regulates Mouse Cortical Development.
A Functional Switch of NuRD Chromatin Remodeling Complex Subunits Regulates Mouse Cortical Development.
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DOI：
10.1016/j.celrep.2016.10.022
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发表时间：
2016-11-01
期刊：
影响因子：
8.8
通讯作者：
Riccio A
中科院分区：
文献类型：
--
作者：
Nitarska J;Smith JG;Sherlock WT;Hillege MM;Nott A;Barshop WD;Vashisht AA;Wohlschlegel JA;Mitter R;Riccio A
组蛋白修饰和染色质重塑代表了细胞使其转录反应适应快速变化的环境条件的普遍机制。在神经元发育过程中发生广泛的染色质重塑，允许多能细胞转变为分化的神经元。在这里，我们报告说，NuRD复合物，这对夫妇ATP依赖的染色质重塑与组蛋白去乙酰化酶活性，调节小鼠大脑发育。亚单位交换的CHDs，核心ATP酶亚单位的NuRD复合物，是必需的不同方面的皮质发育。而CHD4促进祖细胞的早期增殖，CHD5促进神经元迁移和CHD3确保适当的层规格。每种CHD的抑制导致神经元分化和迁移的缺陷，这不能通过表达异源CHD来挽救。最后，我们证明了含有特定CHDs的NuRD复合物被招募到调控元件中，并调节大脑发育所必需的基因的表达。ATP酶CHD3、CHD4和CHD5是NuRD复合物的互斥亚基CHD3、CHD4和CHD5调节皮质发育的不同和非冗余方面。每种CHD的缺失导致神经元增殖和迁移的特定缺陷CHD3、CHD4和CHD5调节脑发育所必需的不同基因组神经发育需要主动染色质重塑。Nitarska等人在小鼠胚胎皮质发育过程中鉴定不同的NuRD染色质重塑复合物，含有CHD3，CHD4或CHD5。CHD4促进基底祖细胞的增殖，而CHD5促进早期放射状迁移，CHD3驱动神经元的晚期迁移和层状特化。
Histone modifications and chromatin remodeling represent universal mechanisms by which cells adapt their transcriptional response to rapidly changing environmental conditions. Extensive chromatin remodeling takes place during neuronal development, allowing the transition of pluripotent cells into differentiated neurons. Here, we report that the NuRD complex, which couples ATP-dependent chromatin remodeling with histone deacetylase activity, regulates mouse brain development. Subunit exchange of CHDs, the core ATPase subunits of the NuRD complex, is required for distinct aspects of cortical development. Whereas CHD4 promotes the early proliferation of progenitors, CHD5 facilitates neuronal migration and CHD3 ensures proper layer specification. Inhibition of each CHD leads to defects of neuronal differentiation and migration, which cannot be rescued by expressing heterologous CHDs. Finally, we demonstrate that NuRD complexes containing specific CHDs are recruited to regulatory elements and modulate the expression of genes essential for brain development. The ATPases CHD3, CHD4, and CHD5 are mutually exclusive subunits of the NuRD complex CHD3, CHD4, and CHD5 regulate distinct and non-redundant aspects of cortical development Loss of each CHD leads to specific defects of neuronal proliferation and migration CHD3, CHD4, and CHD5 regulate distinct set of genes essential for brain development Neural development requires active chromatin remodeling. Nitarska et al. identify distinct NuRD chromatin remodeling complexes, containing CHD3, CHD4, or CHD5, during mouse embryonic cortical development. CHD4 promotes proliferation of basal progenitors, while CHD5 facilitates early radial migration and CHD3 drives late migration and laminar specification of neurons.
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影响因子：
10.5
作者：
Arnold, Sebastian J.;Huang, Guo-Jen;Groszer, Matthias
通讯作者：
Groszer, Matthias
影响因子：
16.2
作者：
Hevner, RF;Shi, LM;Rubenstein, JLR
通讯作者：
Rubenstein, JLR
影响因子：
13.9
作者：
Barnes AP;Polleux F
通讯作者：
Polleux F
DOI：
10.1038/nrg2485
发表时间：
2009-01
期刊：
Nature reviews. Genetics
影响因子：
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作者：
通讯作者：
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影响因子：
64.8
作者：
通讯作者：
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