In this review, we attempt to discuss emerging themes in the regulation of neuronal activity-regulated genes, focusing primarily on an important subset of immediate-early genes. We first discuss earlier studies that have illuminated the role of cis-acting elements within the promoters of immediate-early genes, the corresponding transcription factors that bind these elements, and the roles of major activity-regulated signaling pathways. However, our emphasis is on new studies that have revealed an important role for epigenetic and topological mechanisms, including enhancer-promoter interactions, enhancer RNAs (eRNAs), and activity-induced DNA breaks, that have emerged as important factors that govern the temporal dynamics of activity-induced gene transcription.
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