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

Nitarska, J; Smith, JG; Sherlock, WT; Hillege, MM; Nott, A; Barshop, WD; Vashisht, AA; ... Riccio, A; + view all (2016) A Functional Switch of NuRD Chromatin Remodeling Complex Subunits Regulates Mouse Cortical Development. Cell Rep , 17 (6) pp. 1683-1698. 10.1016/j.celrep.2016.10.022. Green open access

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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.

Type: Article
Title: A Functional Switch of NuRD Chromatin Remodeling Complex Subunits Regulates Mouse Cortical Development
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2016.10.022
Publisher version: http://dx.doi.org/10.1016/j.celrep.2016.10.022
Additional information: © 2016 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: CHD proteins, NuRD complex, chromatin remodeling, cortical development, cortical laminar fate specification, epigenetics, mouse brain, neural progenitors, neural radial migration
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1527115
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