Histone Variants in Neuronal Transcription and Behavioral Regulation

The nucleosomal packaging of DNA by histone octamers provides a substrate for dynamic gene regulation, allowing cells to promote or inhibit transcription by modulating local chromatin structure and accessibility through post-translational histone modification, nucleosome remodeling, and deposition of histone variants. This chapter discusses mechanisms by which neurons diversify the histone landscape across the activity-regulated neuronal genome, in support of temporally specific activity-regulated gene expression. In particular, we focus on replication-independent histone variants, which accumulate in post-mitotic neurons and exhibit variant-specific regulation of gene expression in the context of neuronal activity and behavior. We summarize notable and recent findings on the role histone variants and modifications in activity-regulated transcription and neuronal processes that engage activity-regulated genes and outline unanswered questions, and future directions in the field. We suggest that histone variants serve to endow neuronal chromatin with variant-specific features that facilitate the temporally precise expression of activity-regulated genes, and further describe the relevance of histone variant-mediated gene regulation to aspects of behavior.