Article

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: 15.98). 08/2007; 55(2):201-15. DOI: 10.1016/j.neuron.2007.06.019
Source: PubMed

ABSTRACT 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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    • "BAF45a is a member of a family of mutually exclusive SWI/SNF subunits (BAF45a, b, c, d), unique to metazoans, all of which contain tandem PHD fingers at their C termini. Complexes contain BAF45a appear to be associated with dividing cells, during neural development; for example, BAF45a is switched for BAF45b or BAF45c as proliferating neural stem and progenitor cells transition into post-mitotic neurons (Lessard et al., 2007). The region of BAF45a similar in sequence to INI1 is N-terminal to the PHD domains and is not found in other family members. "
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    • "Posttranslational modification of the transcription factor or chromatin remodeling complex that modulates recruitment has been also been observed (Yu et al., 2013). Finally, developmental modulation remodeling complex composition can provide cell-type-specific transcription factor interaction surfaces (Lessard et al., 2007; Yoo et al., 2009; Goljanek-Whysall et al., 2014). The latter two mechanisms have not yet been described in plants. "
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