An intriguing characteristic of enhancer-promoter interactions

Background It is still challenging to predict interacting enhancer-promoter pairs (IEPs), partially because of our limited understanding of their characteristics. To understand IEPs better, here we studied the IEPs in nine cell lines and nine primary cell types. Results By measuring the bipartite clustering coefficient of the graphs constructed from these experimentally supported IEPs, we observed that one enhancer is likely to interact with either none or all of the target genes of another enhancer. This observation implies that enhancers form clusters, and every enhancer in the same cluster synchronously interact with almost every member of a set of genes and only this set of genes. We perceived that an enhancer can be up to two megabase pairs away from other enhancers in the same cluster. We also noticed that although a fraction of these clusters of enhancers do overlap with super-enhancers, the majority of the enhancer clusters are different from the known super-enhancers. Conclusions Our study showed a new characteristic of IEPs, which may shed new light on distal gene regulation and the identification of IEPs.

Automated summary

By studying IEPs in nine cell lines and nine primary cell types, it was found that enhancers may form clusters, with enhancers in the same cluster interacting synchronously with a set of genes and potentially being up to two million base pairs away from each other. While some clusters of enhancers overlap with super-enhancers, the majority of enhancer clusters are distinct from known super-enhancers.