Convergence of Developmental and Oncogenic Signaling Pathways at Transcriptional Super-Enhancers
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Author(s)
Hnisz, Denes
Schuijers, Jurian
Lin, Charles Y.
Abraham, Brian J.
Lee, Tong Ihn
Bradner, James E.
Weintraub, Abraham Selby
Young, Richard A.
Date Issued
March 2015
Journal
Molecular Cell
Publisher
Elsevier
Citation
Hnisz, Denes et al. “Convergence of Developmental and Oncogenic Signaling Pathways at Transcriptional Super-Enhancers.” Molecular Cell 58.2 (2015): 362–370.
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.molcel.2015.02.014
