Recurrent enhancer-promoter interactions across samples

Abstract

Enhancer-promoter interactions (EPIs) are fundamental to gene regulation, and understanding their recurrence across diverse biological samples is key to deciphering chromatin architecture. In this study, we systematically analyzed the recurrence of EPIs across 49 Hi-C and 95 HiChIP datasets. We found that the majority of EPIs identified in a given sample were also present in other samples, regardless of the assay type (Hi-C or HiChIP) or the enhancer annotations used. Interestingly, EPIs that appeared unique to individual samples were typically surrounded by fewer neighboring EPIs, suggesting they may not represent truly sample-specific interactions. Our findings indicate that most human EPIs have already been captured and that cells primarily reuse subsets of these shared EPIs across different cell types and conditions. This study provides new insights into the pervasive and reusable nature of EPIs in the human genome, with important implications for chromatin conformation studies.