NuRD independent Mi2 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 are ill-defined. Furthermore, evidence from several species suggests that Mi-2 may be incorporated into multiple complexes that may not incorporate histone deacetylase activity. Here, we show that Mi-2 activity is required for suppressing the ectopic expression of germline genes in neurons independently of HDAC1/NuRD, whilst components of the NuRD complex including Mi-2 regulate neural gene expression to ensure proper development of the larval nervous system. We find that Mi-2 and NuRD-associated repression of ectopic gene expression is restricted to the early stages of neuronal development, indicating that newly derived neurons are more sensitive to epigenetic perturbations. Overall design: We performed targeted DamID (TaDa) experiments to determine NuRD component chromatin association in multiple cell types in the developing Drosophila brain. RNA-seq was also performed on brains in which Mi2 was knocked down by RNA interference.