A Functional Switch of NuRD Chromatin Remodeling Complex Subunits Regulates Mouse Cortical Development

Cell Rep. 2016 Nov 1;17(6):1683-1698. doi: 10.1016/j.celrep.2016.10.022.


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.

Keywords: CHD proteins; NuRD complex; chromatin remodeling; cortical development; cortical laminar fate specification; epigenetics; mouse brain; neural progenitors; neural radial migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Movement
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / metabolism*
  • Chromatin Assembly and Disassembly*
  • Gene Deletion
  • Gene Expression Regulation, Developmental
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism*
  • Mice, Inbred C57BL
  • Microcephaly / pathology
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Subunits / metabolism*


  • Protein Subunits
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex