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Mol Cell. 2015 Apr 16;58(2):362-70. doi: 10.1016/j.molcel.2015.02.014. Epub 2015 Mar 19.

Convergence of developmental and oncogenic signaling pathways at transcriptional super-enhancers.

Author information

1
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
2
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
3
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: young@wi.mit.edu.

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.

PMID:
25801169
PMCID:
PMC4402134
DOI:
10.1016/j.molcel.2015.02.014
[Indexed for MEDLINE]
Free PMC Article

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