Chromatin Remodelers in Neuronal Gene Transcription

Chromatin remodelers are evolutionarily conserved multiprotein complexes, which use ATP to regulate the eukaryotic chromatin landscape. From activity-regulated neuronal gene expression to facilitating major protein interaction hubs, the BAF complex serves as a multifaceted remodeler with unique biochemical, structural, and epigenetic functions. In this chapter, we emphasize the neuron-specific BAF (nBAF) complex as a key driver of neuronal gene transcription. Composed of unique subunits assembled in a modular fashion, this chromatin remodeler permits transcriptional responses in response to nuclear and synaptic signals. The BAF complex governs gene expression by regulating enhancer–promoter interactions, promoter-proximal polymerase pausing, and interactions of transcription factors and kinases with the transcription machinery. Recent studies have revealed a strong correlation between neurodevelopmental disorders and mutations in the subunits encoding the BAF complexes. Such BAF gene mutations hint at potential underlying mechanisms of disease etiology that remains underexplored. These mechanisms may involve emerging concepts like liquid–liquid phase separation of BAF complexes and other unknown roles of intrinsically disordered regions found within BAF subunits. Collectively, this chapter focuses on the BAF complex as a critical regulator of activity-coupled neuronal gene expression and explores potential novel mechanisms of neurodevelopmental disorders involving the complex.