Abstract
The nucleosome remodeling and deacetylase (NuRD) complex presents one of the major chromatin remodeling complexes in mammalian cells. Here, we discuss current evidence for NuRD’s role as an important epigenetic regulator of gene expression in neural stem cell (NSC) and neural progenitor cell (NPC) fate decisions in brain development. With the formation of the cerebellar and cerebral cortex, NuRD facilitates experience-dependent cerebellar plasticity and regulates additionally cerebral subtype specification and connectivity in postmitotic neurons. Consistent with these properties, genetic variation in NuRD’s subunits emerges as important risk factor in common polygenic forms of neurodevelopmental disorders (NDDs) and neurodevelopment-related psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BD). Overall, these findings highlight the critical role of NuRD in chromatin regulation in brain development and in mental health and disease.
Highlights
Epigenetic mechanisms are key to establish stable yet malleable gene expression during development and beyond (Jaenisch and Bird, 2003; Sweatt, 2013)
nucleosome remodeling and deacetylase (NuRD) controls synaptic plasticity, neuronal connectivity, and neuronal subtype specification. Consistent with these activities, genetic variations in these genes are important risk factors in common polygenic forms of neurodevelopmental disorders (NDDs) and neurodevelopment-related psychiatric disorders such as SCZ and bipolar disorder (BD). These findings highlight the role of NuRD in chromatin regulation in brain development, and in mental health and disease
Biochemical and genetic studies have shown that NuRD combines ATPase/helicase and histone deacetylation activities in chromatin remodeling
Summary
Epigenetic mechanisms are key to establish stable yet malleable gene expression during (neuro-) development and beyond (Jaenisch and Bird, 2003; Sweatt, 2013). Major epigenetic mechanisms consist of covalent DNA modifications (e.g., CpG methylation), posttranslational modifications (PTMs) of core histones, nucleosome positioning, and noncoding RNA (Jaenisch and Bird, 2003; Schübeler, 2015; Yadav et al, 2018). All of these act tightly together in the control of gene expression. Nucleosome remodeling and deacetylase (NuRD) presents one of four major ATP (adenosine triphosphate)-dependent chromatin remodeling complexes and has been identified originally as a transcriptional silencer (Ho and Crabtree, 2010) This view has been revised in light of NuRD’s multifarious effects on gene transcription, including gene activation, in embryonic development, cancer, and aging (Lai and Wade, 2011). Concluding, we consider further steps to be taken to corroborate NuRD’s function in mental health and disease and how such knowledge may help to reframe current disease concepts
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