Wu Jiang I, Lessard Julie, Olave Ivan A, Qiu Zilong, Ghosh Anirvan, Graef Isabella A, Crabtree Gerald R
Howard Hughes Medical Institute and Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
Neuron. 2007 Oct 4;56(1):94-108. doi: 10.1016/j.neuron.2007.08.021.
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 Ca(2+)-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.
树突形态的多样性是神经元的基本特征之一，部分受电活动启动的转录程序调控。我们发现，树突生长需要一类组合组装的、神经元特异性染色质重塑复合物（nBAF复合物），其以肌动蛋白相关蛋白BAF53b为特征，并基于Brg/Brm ATP酶。nBAF复合物紧密结合钙离子响应性树突调节因子CREST，并直接调控树突生长所必需的基因。BAF53b对于nBAF复合物的组装或与CREST的相互作用并非必需，但却是它们被招募到特定靶基因启动子所必需的。高度同源的BAF53a蛋白是神经祖细胞和非神经BAF复合物的一个组分，不能替代BAF53b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BAF53b的肌动蛋白折叠亚结构域2赋予的。这些研究表明，编码BAF复合物各个亚基的基因的功能就像一个由十个字母组成的单词中的字母，通过其产物的组合组装产生生物学上的特定意义（在这种情况下是树突生长）。
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