Figure 1

Conjectured chromatin architecture. The schematic drawing depicts TADs as chromatin loops bounded by regions of high architectural protein (AP) occupancy (multicolored objects), as proposed by Van Bortle et al.[1]. These are conjectured to interact with an unknown nuclear structure that provides topological constraints. The size of a TAD is determined by the density of interactions within the TAD. These are provided by APs, so that a relatively high density of AP binding sites results in a smaller TAD. Might the density of interactions provide a sufficient ‘gravitational’ pull to hold the chromatin of a TAD physically together and therefore in a preferentially interacting network? It is more difficult to explain how regions within a large TAD are prevented from interacting with regions in another large TAD. Patterns of gene activity or silencing and associated factors may also contribute to close the interaction horizon of TAD sequences.