Figure 4.
Supercoiling ensures the fidelity of enhancer–promoter interactions. (a) Schematic presentation of a situation where one enhancer (E) shows the same affinity to two promoters (P) that are at the same genomic distance from it but where one (P1) is located in the same and other (P2) in the neighbouring topological domain. To be able to introduce supercoiling the neighbouring chromatin loops were modelled as two closed loops tethered to each other. (b) Intra-domain enhancer–promoter interactions are favoured (red profile), whereas inter-domain ones are disfavoured by DNA supercoiling (green profile). The inset shows how supercoiling increases the ‘preference’ of an enhancer for intra- versus inter-domain interaction. Already without supercoiling there is a 2–3-fold preference of the enhancer to interact with the promoter located in the same domain. However, with supercoiling a 20-fold preference can easily be reached. The two simulation snapshots reflect the observation that without supercoiling (at ε = 8 kBT) the modelled enhancers and promoters only rarely interact with each other, whereas with increasing supercoiling one frequently observes intra-domain enhancer–promoter contacts. (c) ‘Ideogramic’ presentation showing the effect of supercoiling on the structure of topological domains and on the intra-domain preference of enhancer–promoter interaction.