The influence of genome organization on transcription is central to our understanding of cell type specification. Higher-order genome organization is established through short- and long-range DNA interactions. Coordination of these interactions, from single atoms to entire chromosomes, plays a fundamental role in transcriptional control of gene expression. Loss of this coupling can result in disease. Analysis of transcriptional regulation typically involves disparate experimental approaches, from structural studies that define angstrom-level interactions to cell-biological and genomic approaches that assess mesoscale relationships. Thus, to fully understand the mechanisms that regulate gene expression, it is critical to integrate the findings gained across these distinct size scales. In this review, I illustrate fundamental ways in which cells regulate transcription in the context of genome organization.
