An Essential Switch in Subunit Composition of a Chromatin Remodeling Complex during Neural Development

Howard Hughes Medical Institute and Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
Neuron (Impact Factor: 15.05). 08/2007; 55(2):201-15. DOI: 10.1016/j.neuron.2007.06.019
Source: PubMed


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 Krüppel/PHD domain protein and the actin-related protein BAF53a are quantitatively associated with the SWI2/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.

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Article: An Essential Switch in Subunit Composition of a Chromatin Remodeling Complex during Neural Development

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    • "transient amplifying progenitors (TAPs) and Doublecortin (DCX)+ neuroblasts (Figures S1D and S1E and data not shown). Importantly , we also observed the expression of BAF53a and BAF45a (Figures S1F and S1G; but not BAF45b and BAF53b, Figures S1H and S1I), subunits characterizing the neural-progenitor-specific BAF complexes (Lessard et al., 2007). Conversely, Pax6 immunoreactivity is largely restricted to neuroblasts in the SEZ and rostral migratory stream (RMS), where it colocalizes with Brg1 (Figures 1D and 1E). "

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    • "Understanding the roles of BAF complexes in murine neural development so far has been based on data from phenotypic analyses of neural cell-type-specific mouse mutants of genes encoding the ATPase subunit Brg1 and some other BAF subunits (Bischof et al., 2015; Lessard et al., 2007; Matsumoto et al., 2006; Ninkovic et al., 2013; Tuoc et al., 2013a; Vogel-Ciernia et al., 2013; Weider et al., 2012; Wu et al., 2007; Yu et al., 2013). In ATPase Brg1-deficient neural cells, other BAF subunits are expressed at normal levels and are incorporated into ATPase Brm-based complexes (Lessard et al., 2007). In addition, the loss of both Brg1 and Brm subunits does not affect the expression of other BAF subunits in cancer cell lines (Strobeck et al., 2002). "
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    • "The CHD family of nucleosome remodelers is defined by ATPase proteins with chromodomains, which bind methylated lysine residues in histone tails (Lessard et al. 2007). CHD3/4 ATPases are essential for nucleosome remodeling activity in the Mi-2/NuRD complex. "
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