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Using chromatin 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 (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).

SciBX 6(16); doi:10.1038/scibx.2013.402
Published online April 25, 2013

Patent application filed for findings from both studies; licensed to Syros Pharmaceuticals Inc.

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.