Abstract
3D genome folding enables the physical storage of chromosomes into the compact volume of a cell's nucleus, allows for the accurate segregation of chromatin to daughter cells, and has been shown to be tightly coupled to the way in which genetic information is converted into transcriptional programs [1-3]. Importantly, this link between chromatin architecture and gene regulation is a selectable feature in which modifications to chromatin organization accompany, or perhaps even drive the establishment of new regulatory strategies with enduring impacts on animal body plan complexity. Here, we discuss the nature of different 3D genome folding systems found across the tree of life, with particular emphasis on metazoans, and the relative influence of these systems on gene regulation. We suggest how the properties of these folding systems have influenced regulatory strategies employed by different lineages and may have catalyzed the partitioning and specialization of genetic programs that enabled multicellularity and organ-grade body plan complexity.