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

Neuron. 2007 Jul 19;55(2):201-15. doi: 10.1016/j.neuron.2007.06.019.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Chromatin Assembly and Disassembly / genetics
  • Chromatin Assembly and Disassembly / physiology*
  • Epigenesis, Genetic / genetics
  • Epigenesis, Genetic / physiology
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Mice
  • Molecular Sequence Data
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuroepithelial Cells / cytology
  • Neuroepithelial Cells / metabolism
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Neurons / cytology*
  • Neurons / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Multienzyme Complexes
  • Nerve Tissue Proteins
  • Protein Subunits
  • Transcription Factors