We discuss the origins of three models for the structure of chromosomes in multi-cellular animals: CTCF/cohesin loop extrusion, compartments and boundary-boundary pairing. We then review what is known about the properties of TAD (topologically associating domains) boundary elements in flies, and how these properties are deployed in generating TADs and controlling the utilization of genetic information. We discuss another class of elements that function by physically pairing with each other and their special roles in regulating gene activity. We show that TADs are organized into large TAD neighborhoods, and that neighborhoods are a common structural feature in multicellular animals. We discuss possible models for the structure of the main chromosomal axis and the underlying mechanisms for homolog/sister chromosome pairing.
Ke et al. (Wed,) studied this question.