Thursday, April 25, 2013
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immunoprecipitation followed by whole-genome sequencing (ChIP-Seq) to
identify disease-associated super-enhancer regulatory elements
Cell culture studies
suggest mapping super-enhancers could help identify drug targets in cancer or
other diseases. ChIP-Seq of mediator
complex subunit 1 (MED1)
in multiple myeloma (MM) cells identified 308 highly enriched sites of MED1
binding upstream of known oncogenic drivers, including c-Myc
These enriched MED1-bound regions were dubbed super-enhancers because they
were bound by multiple transcriptional regulators of cell fate and drove
target gene expression to higher levels than traditional enhancers. In MM
cells, a bromodomain
containing 4 (BRD4)
inhibitor decreased expression of super-enhancer-regulated genes compared
with that of genes not associated with super-enhancers. Next steps include
identifying molecules to disrupt super-enhancer function and using
super-enhancer mapping to identify drug targets (see Super-enhancing
discovery, page 1).
Published online April 25, 2013
Patent application filed
for findings from both studies; licensed to Syros
Whyte, W.A. et al. Cell;
published online April 11, 2013;
Lovén, J. et al. Cell; published online April 11, 2013;
Contact: Richard Young, Whitehead Institute for Biomedical
Research, Cambridge, Mass.
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