New Genome-Wide Technologies to Study Activity-Regulated Transcription

Activity-driven transcription is a critical step in the response of neurons to stimuli. It is initiated by an increase in intracellular Ca2+ at activated synapses that triggers a cascade of phosphorylation events regulated by calcium-dependent kinases, including the activation of specific transcription factors (TFs). These TFs, in turn, mediate changes in gene expression that extend the temporal impact of neuronal activation. More recently, other activity-driven changes affecting the occupancy, accessibility, and conformation of chromatin have been discovered. The dysregulation of these pathways may have important implications for different brain disorders. The rapid development and improvement of new techniques for the analysis of the transcriptome and epigenome based on next-generation sequencing (NGS) have made possible the identification of hundreds of genes whose expression is activity-regulated, revealing the complexity of activity-driven gene expression. In this chapter, we introduce the great variety of techniques available for transcriptome and epigenome analysis, discuss relevant parameters for the design of NGS experiments in the nervous system, and summarize the genomic insights acquired in the last decade about the activity-driven mechanisms underlying plasticity-related changes in neuronal gene expression.