Convergence of Developmental and Oncogenic Signaling Pathways at Transcriptional Super-Enhancers
Author(s)Hnisz, Denes; Schuijers, Jurian; Lin, Charles Y.; Abraham, Brian J.; Lee, Tong Ihn; Bradner, James E.; Weintraub, Abraham Selby; Young, Richard A; ... Show more Show less
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Super-enhancers and stretch enhancers (SEs) drive expression of genes that play prominent roles in normal and disease cells, but the functional importance of these clustered enhancer elements is poorly understood, so it is not clear why genes key to cell identity have evolved regulation by such elements. Here we show that SEs consist of functional constituent units that concentrate multiple developmental signaling pathways at key pluripotency genes in embryonic stem cells and confer enhanced responsiveness to signaling of their associated genes. Cancer cells frequently acquire SEs at genes that promote tumorigenesis, and we show that these genes are especially sensitive to perturbation of oncogenic signaling pathways. Super-enhancers thus provide a platform for signaling pathways to regulate genes that control cell identity during development and tumorigenesis.
DepartmentMassachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Hnisz, Denes et al. “Convergence of Developmental and Oncogenic Signaling Pathways at Transcriptional Super-Enhancers.” Molecular Cell 58.2 (2015): 362–370.
Author's final manuscript