An essential switch in subunit composition of a chromatin remodeling complex during neural development

被引:582
作者
Lessard, Julie
Wu, Jiang I.
Ranish, Jeffrey A.
Wan, Mimi
Winslow, Monte M.
Staahl, Brett T.
Wu, Hai
Aebersold, Ruedi
Graef, Isabella A.
Crabtree, Gerald R.
机构
[1] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA
[2] Inst Syst Biol, Seattle, WA 98103 USA
关键词
D O I
10.1016/j.neuron.2007.06.019
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
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 IBAF53a are quantitatively associated with the SW12/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.
引用
收藏
页码:201 / 215
页数:15
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