title: Epigenomic enhancer profiling defines a signature of colon cancer.
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.
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Batool
authors.initials: B
authors.lastname: Akhtar-Zaidi
authors.forename: Richard
authors.initials: R
authors.lastname: Cowper-Sal-lari
authors.forename: Olivia
authors.initials: O
authors.lastname: Corradin
authors.forename: Alina
authors.initials: A
authors.lastname: Saiakhova
authors.forename: Cynthia F
authors.initials: CF
authors.lastname: Bartels
authors.forename: Dheepa
authors.initials: D
authors.lastname: Balasubramanian
authors.forename: Lois
authors.initials: L
authors.lastname: Myeroff
authors.forename: James
authors.initials: J
authors.lastname: Lutterbaugh
authors.forename: Awad
authors.initials: A
authors.lastname: Jarrar
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Kalady
authors.forename: Joseph
authors.initials: J
authors.lastname: Willis
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Tesar
authors.forename: Thomas
authors.initials: T
authors.lastname: Laframboise
authors.forename: Sanford
authors.initials: S
authors.lastname: Markowitz
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lupien
authors.forename: Peter C
authors.initials: PC
authors.lastname: Scacheri
mesh_terms: D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D056426:Genetic Loci; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008745:Methylation; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D059467:Transcriptome
chemical_list: D006657:Histones