Hay, D. et al. Nat. Genet. 48, 895–903 (2016).

Super-enhancers are a recently described class of transcriptional regulators that are thought to be more than the sum of their parts and exert higher-order control. Hay et al. focused on a super-enhancer in the α-globin locus with features that fit the current definition: multiple enhancers in close proximity, binding of the Mediator complex and acetylation of histone H3 at lysine 27. They characterized transcription factor binding at the five enhancer-like elements found in this 24-kb region as well as the impact of single and double enhancer knockouts. All enhancer elements acted in an additive manner, and no single element was critical for globin expression or chromatin structure. The authors stress that new classes of transcriptional regulators should be subject to functional analysis because, at least for the α-globin locus in mouse erythroid cells, there is no evidence of a super-enhancer.