Regulation of dendritic development by NeuronSpecific chromatin remodeling complexes
Regulation of dendritic development by NeuronSpecific chromatin remodeling complexes
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DOI：
10.1016/j.neuron.2007.08.021
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发表时间：
2007-10-04
期刊：
影响因子：
16.2
通讯作者：
Crabtree, Gerald R.
中科院分区：
文献类型：
--
作者：
Wu, Jiang I.;Lessard, Julie;Crabtree, Gerald R.
树突模式的多样性是神经元的基本特征之一，并且部分地受由电活动启动的转录程序的调节。我们发现，树突状生长需要一个家庭的组合组装，神经元特异性染色质重塑复合物（nBAF复合物）区分肌动蛋白相关蛋白BAF 53 b和基于Brg/Brm ATP酶。nBAF复合物与Ca 2 +-响应性树突调节剂CREST紧密结合，并直接调节树突生长所必需的基因。BAF 53 b不是nBAF复合物组装或与CREST相互作用所必需的，但却是它们募集到特定靶基因启动子所必需的。高度同源的BAF 53 a蛋白是神经祖细胞和非神经BAF复合物的组成部分，不能取代BAF 53 b在树突发育中的作用。值得注意的是，我们发现这种功能特异性是由BAF 53 b的肌动蛋白折叠亚结构域2赋予的。这些研究表明，编码BAF复合物的各个亚基的基因的功能就像一个十个字母的单词中的字母一样，通过组合组装它们的产物来产生生物学上特定的含义（在这种情况下是树突状生长）。
The diversity of dendritic patterns is one of the fundamental characteristics of neurons and is in part regulated by transcriptional programs initiated by electrical activity. We show that dendritic outgrowth requires a family of combinatorially assembled, neuron-specific chromatin remodeling complexes (nBAF complexes) distinguished by the actin-related protein BAF53b and based on the Brg/Brm ATPases. nBAF complexes bind tightly to the Ca2+, -responsive dendritic regulator CREST and directly regulate genes essential for dendritic outgrowth. BAF53b is not required for nBAF complex assembly or the interaction with CREST, yet is required for their recruitment to the promoters of specific target genes. The highly homologous BAF53a protein, which is a component of neural progenitor and nonneural BAF complexes, cannot replace BAF53b's role in dendritic development. Remarkably, we find that this functional specificity is conferred by the actin fold subdomain 2 of BAF53b. These studies suggest that the genes encoding the individual subunits of BAF complexes function like letters in a ten-letter word to produce biologically specific meanings (in this case dendritic outgrowth) by combinatorial assembly of their products.