Faculty Collaboration Database

Chromatin interactions and candidate genes at ten prostate cancer risk loci. Sci Rep 2016 Mar 16;6:23202

Date

03/17/2016

Pubmed ID

26979803

Pubmed Central ID

PMC4793270

DOI

10.1038/srep23202

Scopus ID

2-s2.0-84982187267 (requires institutional sign-in at Scopus site)   33 Citations

Abstract

Genome-wide association studies have identified more than 100 common single nucleotide polymorphisms (SNPs) that are associated with prostate cancer risk. However, the vast majority of these SNPs lie in noncoding regions of the genome. To test whether these risk SNPs regulate their target genes through long-range chromatin interactions, we applied capture-based 3C sequencing technology to investigate possible cis-interactions at ten prostate cancer risk loci in six cell lines. We identified significant physical interactions between risk regions and their potential target genes including CAPG at 2p11.2, C2orf43 at 2p24.1, RFX6 at 6q22.1, NFASC at 1q32.1, MYC at 8q24.1 and AGAP7P at 10q11.23. Most of the interaction peaks were co-localized to regions of active histone modification and transcription factor binding sites. Expression quantitative trait locus (eQTL) analysis showed suggestive eQTL signals at rs1446669, rs699664 and rs1078004 for CAPG (p < 0.004), rs13394027 for C2orf43 (p = 2.25E-27), rs10993994 and rs4631830 for AGAP7P (p < 8.02E-5). Further analysis revealed an enhancer activity at genomic region surrounding rs4631830 which was expected to disrupt HOXB-like DNA binding affinity. This study identifies a set of candidate genes and their potential regulatory variants, and provides additional evidence showing the role of long-range chromatin interactions in prostate cancer etiology.

Author List

Du M, Tillmans L, Gao J, Gao P, Yuan T, Dittmar RL, Song W, Yang Y, Sahr N, Wang T, Wei GH, Thibodeau SN, Wang L

MESH terms used to index this publication - Major topics in bold

Cell Line, Tumor
Chromatin
Epigenesis, Genetic
Gene Expression
Gene Expression Regulation, Neoplastic
Genes, Neoplasm
Genetic Association Studies
Genetic Loci
Genetic Predisposition to Disease
Humans
Male
Molecular Sequence Annotation
Polymorphism, Single Nucleotide
Prostatic Neoplasms
Risk
Sequence Analysis, DNA