Super-Enhancers in the Control of Cell Identity and Disease

Super-enhancers are large clusters of transcriptional enhancers that drive expression of genes that define cell identity. Improved understanding of the roles that super-enhancers play in biology would be afforded by knowing the constellation of factors that constitute these domains and by identifying super-enhancers across the spectrum of human cell types. We describe here the population of transcription factors, cofactors, chromatin regulators, and transcription apparatus occupying super-enhancers in embryonic stem cells and evidence that super-enhancers are highly transcribed. We produce a catalog of super-enhancers in a broad range of human cell types and find that super-enhancers associate with genes that control and define the biology of these cells. Interestingly, disease-associated variation is especially enriched in the super-enhancers of disease-relevant cell types. Furthermore, we find that cancer cells generate super-enhancers at oncogenes and other genes important in tumor pathogenesis. Thus, super-enhancers play key roles in human cell identity in health and in disease. [Display omitted] •Catalog of super-enhancers in 86 human cell and tissue types•Disease-associated sequence variation is enriched in super-enhancers•Cancer cells generate super-enhancers at key tumor pathogenesis genes•Super-enhancers provide biomarkers for disease diagnosis and therapy Super-enhancers in 86 human cell types have been cataloged. Disease-associated sequence variation is enriched in super-enhancers, and cancer cells generate super-enhancers at key tumor pathogenesis genes.