The NuRD Complex in Neurodevelopment and Disease: A Case of Sliding Doors

Abstract

The Nucleosome Remodelling and Deacetylase (NuRD) complex represents one of the major chromatin remodelling complexes in mammalian cells, uniquely coupling the ability to “open” the chromatin by inducing nucleosome sliding with histone deacetylase activity. At the core of the NuRD complex are a family of ATPases named CHDs that utilise the energy produced by the hydrolysis of the ATP to induce chromatin structural changes. Recent studies have highlighted the prominent role played by the NuRD in regulating gene expression during brain development and in maintaining neuronal circuitry in the adult cerebellum. Importantly, components of the NuRD complex have been found to carry mutations that profoundly affect neurological and cognitive development in humans. Here, we discuss recent literature concerning the molecular structure of NuRD complexes and how the subunit composition and numerous permutations greatly determine their functions in the nervous system. We will also discuss the role of the CHD family members in an array of neurodevelopmental disorders. Special emphasis will be given to the mechanisms that regulate the NuRD complex composition and assembly in the cortex and how subtle mutations may result in profound defects of brain development and the adult nervous system.

Keywords

• neuroepigenetics
• chromatin remodelling
• NuRD
• CHD4
• neurodevelopment
• neurodegeneration