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Science. 2012 May 11;336(6082):736-9. doi: 10.1126/science.1217277. Epub 2012 Apr 12.

Epigenomic enhancer profiling defines a signature of colon cancer.

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  • 1Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.

Abstract

Cancer is characterized by gene expression aberrations. Studies have largely focused on coding sequences and promoters, even though distal regulatory elements play a central role in controlling transcription patterns. We used the histone mark H3K4me1 to analyze gain and loss of enhancer activity genome-wide in primary colon cancer lines relative to normal colon crypts. We identified thousands of variant enhancer loci (VELs) that comprise a signature that is robustly predictive of the in vivo colon cancer transcriptome. Furthermore, VELs are enriched in haplotype blocks containing colon cancer genetic risk variants, implicating these genomic regions in colon cancer pathogenesis. We propose that reproducible changes in the epigenome at enhancer elements drive a specific transcriptional program to promote colon carcinogenesis.

PMID:
22499810
[PubMed - indexed for MEDLINE]
PMCID:
PMC3711120
Free PMC Article

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