Four studies recently demonstrated correlations between genetic risk variants and large clusters of active enhancers, similar to locus control regions. These features have been called ‘super-enhancers’ [41,42], ‘stretch enhancers’ [24], ‘multiple enhancers’ [7] and ‘enhancer clusters’ [23], and are similar but not identical between studies, although many of these features overlap. The methods used to identify these clusters are distinct. Super-enhancers, for example, are defined by identifying the top-ranking enhancers on the basis of the levels of associated transcription factors or chromatin marks identified through ChIP studies. Stretch enhancers are defined by stretches of open chromatin more densely and more broadly marked with enhancer-histone modifications than typical enhancers. Despite these differences, many of the defined features overlap. These enhancer clusters are highly cell-type specific and have been proposed to play a predominant role in regulating the cell-type-specific processes that define the biology of a given cell type. Moreover, they are disproportionally enriched for genetic risk variants compared to typical enhancers, and the enrichment is biased toward disease-relevant cell types. These results further support the notion that variants that influence cell-type-specific
