title: An essential switch in subunit composition of a chromatin remodeling complex during neural development.
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.
authors.affiliation: Howard Hughes Medical Institute and Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Lessard
authors.forename: Jiang I
authors.initials: JI
authors.lastname: Wu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Ranish
authors.forename: Mimi
authors.initials: M
authors.lastname: Wan
authors.forename: Monte M
authors.initials: MM
authors.lastname: Winslow
authors.forename: Brett T
authors.initials: BT
authors.lastname: Staahl
authors.forename: Hai
authors.initials: H
authors.lastname: Wu
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.forename: Isabella A
authors.initials: IA
authors.lastname: Graef
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Crabtree
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D046569:Neuroepithelial Cells / Q000166:cytology / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D014157:Transcription Factors