Super-enhancers or stretch enhancers are clusters of active enhancers that often coordinate cell-type specific gene regulation during development and differentiation. In addition, the enrichment of disease-associated single nucleotide polymorphism in super-enhancers indicates their critical function in disease-specific gene regulation. However, little is known about the function of super-enhancers beyond gene regulation.

In this study, through a comprehensive analysis of super-enhancers in 30 human cell/tissue types, we identified a new class of super-enhancers which are constitutively active across most cell/tissue types. These ‘common’ super-enhancers are associated with universally highly expressed genes in contrast to the canonical definition of super-enhancers that assert cell-type specific gene regulation. In addition, the genome sequence of these super-enhancers is highly conserved by evolution and among humans, advocating their universal function in genome regulation. Integrative analysis of 3D chromatin loops demonstrates that, in comparison to the cell-type specific super-enhancers, the cell-type common super-enhancers present a striking association with rapidly recovering loops.

In this study, we propose that a new class of super-enhancers may play an important role in the early establishment of 3D chromatin structure.