Molecular Cell
Volume 58, Issue 2, 16 April 2015, Pages 362-370
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Short Article
Convergence of Developmental and Oncogenic Signaling Pathways at Transcriptional Super-Enhancers

https://doi.org/10.1016/j.molcel.2015.02.014Get rights and content
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Highlights

  • Super-enhancers (SEs) consist of clusters of active enhancers

  • SEs are frequently bound by terminal transcription factors of signaling pathways

  • SE-driven genes are especially responsive to signaling input

  • SEs acquired in cancer cells are responsive to oncogenic signaling

Summary

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.

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