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

Julie Lessard, Jiang I. Wu, Jeffrey A. Ranish, Mimi Wan, Monte M. Winslow, Brett T. Staahl, Hai Wu, Ruedi Aebersold, Isabella A. Graef, Gerald R. Crabtree

Research output: Contribution to journalArticle

446 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)201-215
Number of pages15
JournalNeuron
Volume55
Issue number2
DOIs
StatePublished - Jul 19 2007

Keywords

  • DEVBIO
  • MOLNEURO
  • STEMCELL

ASJC Scopus subject areas

  • Neuroscience(all)

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    Lessard, J., Wu, J. I., Ranish, J. A., Wan, M., Winslow, M. M., Staahl, B. T., Wu, H., Aebersold, R., Graef, I. A., & Crabtree, G. R. (2007). An Essential Switch in Subunit Composition of a Chromatin Remodeling Complex during Neural Development. Neuron, 55(2), 201-215. https://doi.org/10.1016/j.neuron.2007.06.019