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.National Institutes of Health (U.S.) (NIH grant HG002668)National Institutes of Health (U.S.) (NIH grant CA109901)National Institutes of Health (U.S.) (NIH grant CA146445)National Institutes of Health (U.S.) (NIH Roadmap Epigenome Projects and the Rush Alzheimer’s Disease Center at Rush University Medical Center, Chicago (P30AG10161)National Institutes of Health (U.S.) (NIH Roadmap Epigenome Projects and the Rush Alzheimer’s Disease Center at Rush University Medical Center, Chicago (R01AG36042)National Institutes of Health (U.S.) (NIH Roadmap Epigenome Projects and the Rush Alzheimer’s Disease Center at Rush University Medical Center, Chicago (RC2AG36547