NuRD‐independent Mi‐2 activity represses ectopic gene expression during neuronal maturation

During neuronal development, extensive changes to chromatin states occur to regulate lineage‐specific gene expression. The molecular factors underlying the repression of non‐neuronal genes in differentiated neurons are poorly characterised. The Mi2/NuRD complex is a multiprotein complex with nucleosome remodelling and histone deacetylase activity. Whilst NuRD has previously been implicated in the development of nervous system tissues, the precise nature of the gene expression programmes that it coordinates is ill‐defined. Furthermore, evidence from several species suggests that Mi‐2 may be incorporated into multiple complexes that may not possess histone deacetylase activity. We show that Mi‐2 activity is required for suppressing ectopic expression of germline genes in neurons independently of HDAC1/NuRD, whilst components of NuRD, including Mi‐2, regulate neural gene expression to ensure proper development of the larval nervous system. We find that Mi‐2 binding in the genome is dynamic during neuronal maturation, and Mi‐2‐mediated repression of ectopic gene expression is restricted to the early stages of neuronal development, indicating that Mi‐2/NuRD is required for establishing stable neuronal transcriptomes during the early stages of neuronal differentiation.