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Hotspots of aberrant enhancer activity punctuate the colorectal cancer epigenome

ABSTRACT: We sought to identify hotspots of aberrant enhancer activity in colorectal cancer (CRC) through interrogation of the enhancer epigenomes of a large cohort of genetically diverse CRC samples and normal colonic crypts, representing the cell type of origin for CRC. Through characterization of loci that exhibit differential enhancer activity, we identified sets of enhancers that are recurrently commissioned and decommissioned in CRC relative to normal crypts. The set of recurrently commissioned, or “acquired”, enhancers are of particular interest. Many originate from primed chromatin and activate known and potentially novel oncogenes in CRC. They are also frequently constituents of super enhancers and loaded with AP-1 and cohesin complex proteins. Nearly half of all GWAS CRC risk loci identified to date map to these enhancer hotspots. Through functional studies and integrative analyses we further demonstrate that CRC growth can be mitigated through pharmacologic inhibition or targeted knockout of genes activated by recurrent enhancers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE77737 | GEO | 2017/02/08

SECONDARY ACCESSION(S): PRJNA311329

REPOSITORIES: GEO

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