Decoding the Epigenomic Regulation of Neuronal Plasticity

Transcriptional enhancers are regulatory DNA elements that underlie the specificity and dynamic patterns of gene expression. Over the past decade, large-scale functional genomics projects have driven transformative progress in our identification of enhancers and our understanding of the mechanisms by which they regulate gene expression. However, much remains to be learned about how enhancers orchestrate the biology of specific cellular processes including neuronal differentiation and plasticity. Neurons are dynamic cells that respond and adapt to stimuli throughout their long postmitotic lives at least in part by changing their programs of gene transcription. We have been investigating how chromatin regulation at enhancers coordinates these transcriptional adaptations in order to illuminate the roles of enhancers in neuronal biology. I will discuss the evidence and proposed mechanisms for the regulation of chromatin state and structure at enhancers in postmitotic neurons. I will also share data from our ongoing studies, in which we are using CRISPR/dCas-mediated epigenome editing to directly test the functional consequences of enhancer chromatin regulation for both neuronal gene expression and the adaptation of neuronal function.