Higher-Order Genome Organization in the Control of Neuronal Identity and Neural Circuit Plasticity

The genome is organized in the cell nucleus by a series of hierarchical principles that serve to both pack DNA into a nuclear volume of limited size and tightly control the timing and magnitude of gene expression programs. At genomic length scales beyond the nucleosome, gene regulatory regions including promoters, enhancers, and insulator elements associate within topologically associating domains (TADs). Chromosomal regions are also organized around large subnuclear structures including nuclear speckles, nuclear lamina, and the nucleolus, which help establish active or repressive transcriptional environments. In this chapter, we will explore the mechanisms underlying higher-order genome organization, including specialized ones found in postmitotic neurons. We will examine how the different hierarchies of genome organization regulate neuronal identity and neural circuit plasticity in the developing and adult brain. We will especially highlight how activity-dependent remodeling of genome architecture helps to establish the gene expression programs required for long-term memory in animals.