What are super-enhancers?

The term 'super-enhancer' has been used to describe groups of putative enhancers in close genomic proximity with unusually high levels of Mediator binding, as measured by chromatin immunoprecipitation and sequencing (ChIP-seq). Here we review the identification and composition of super-enhancers, describe links between super-enhancers, gene regulation and disease, and discuss the functional significance of enhancer clustering. We also provide our perspective regarding the proposition that super-enhancers are a regulatory entity conceptually distinct from what was known before the introduction of the term. Our opinion is that there is not yet strong evidence that super-enhancers are a novel paradigm in gene regulation and that use of the term in this context is not currently justified. However, the term likely identifies strong enhancers that exhibit behaviors consistent with previous models and concepts of transcriptional regulation. In this respect, the super-enhancer definition is useful in identifying regulatory elements likely to control genes important for cell type specification.