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Publication Detail
A Functional Switch of NuRD Chromatin Remodeling Complex Subunits Regulates Mouse Cortical Development.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Nitarska J, Smith JG, Sherlock WT, Hillege MM, Nott A, Barshop WD, Vashisht AA, Wohlschlegel JA, Mitter R, Riccio A
  • Publication date:
    01/11/2016
  • Pagination:
    1683, 1698
  • Journal:
    Cell Rep
  • Volume:
    17
  • Issue:
    6
  • Status:
    Published
  • Country:
    United States
  • PII:
    S2211-1247(16)31408-5
  • Language:
    ENG
  • Keywords:
    CHD proteins, NuRD complex, chromatin remodeling, cortical development, cortical laminar fate specification, epigenetics, mouse brain, neural progenitors, neural radial migration
Abstract
Histone modifications and chromatin remodeling represent universal mechanisms by which cells adapt their transcriptional response to rapidly changing environmental conditions. Extensive chromatin remodeling takes place during neuronal development, allowing the transition of pluripotent cells into differentiated neurons. Here, we report that the NuRD complex, which couples ATP-dependent chromatin remodeling with histone deacetylase activity, regulates mouse brain development. Subunit exchange of CHDs, the core ATPase subunits of the NuRD complex, is required for distinct aspects of cortical development. Whereas CHD4 promotes the early proliferation of progenitors, CHD5 facilitates neuronal migration and CHD3 ensures proper layer specification. Inhibition of each CHD leads to defects of neuronal differentiation and migration, which cannot be rescued by expressing heterologous CHDs. Finally, we demonstrate that NuRD complexes containing specific CHDs are recruited to regulatory elements and modulate the expression of genes essential for brain development.
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