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

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

Author information

1
MRC Laboratory for Molecular and Cell Biology, University College London, London WC1E 6BT, UK.
2
Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1737 USA.
3
Lincoln's Inn Fields Laboratory, The Francis Crick Institute, London WC2A 3LY, UK.
4
MRC Laboratory for Molecular and Cell Biology, University College London, London WC1E 6BT, UK. Electronic address: a.riccio@ucl.ac.uk.

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.

KEYWORDS:

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

PMID:
27806305
PMCID:
PMC5149529
DOI:
10.1016/j.celrep.2016.10.022
[Indexed for MEDLINE]
Free PMC Article

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