Genome and Epigenome Engineering Approaches to Studying Neuronal Activity-Dependent Transcriptional Enhancers

Neuronal activity-dependent transcription plays a key role in brain plasticity by transducing synaptic activity into changes in the regulation of genes that are required for synapse formation, circuit connectivity, and neuronal firing. Sequencing data have suggested important functions for distal enhancers in shaping the activity-dependent transcriptional response; however, these relationships are correlational and require experimental validation. In this chapter, we review innovative genome and epigenome engineering approaches that are increasingly being deployed to test hypotheses of enhancer-dependent control of neuronal transcription and plasticity. We focus on the highly versatile CRISPR/Cas9 system and highlight studies showing its application in approaches including functional genomics, epigenome editing, chromatin looping, and precision genome editing.