Functional enhancers at the gene-poor 8q24 cancer-linked locus

Li Jia; Gilad Landan; Mark Pomerantz; Rami Jaschek; Paula Herman; David Reich; Chunli Yan; Omar Khalid; Phil Kantoff; William Oh; J Robert Manak; Benjamin P Berman; Brian E Henderson; Baruch Frenkel; Christopher A Haiman; Matthew Freedman; Amos Tanay; Gerhard A Coetzee

doi:10.1371/journal.pgen.1000597

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Functional enhancers at the gene-poor 8q24 cancer-linked locus

Journal article

Open access

Peer reviewed

Functional enhancers at the gene-poor 8q24 cancer-linked locus

Li Jia, Gilad Landan, Mark Pomerantz, Rami Jaschek, Paula Herman, David Reich, Chunli Yan, Omar Khalid, Phil Kantoff, William Oh, …

PLoS genetics, Vol.5(8), pp.e1000597-e1000597

08/2009

DOI: 10.1371/journal.pgen.1000597

PMCID: PMC2717370

PMID: 19680443

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Abstract

Multiple discrete regions at 8q24 were recently shown to contain alleles that predispose to many cancers including prostate, breast, and colon. These regions are far from any annotated gene and their biological activities have been unknown. Here we profiled a 5-megabase chromatin segment encompassing all the risk regions for RNA expression, histone modifications, and locations occupied by RNA polymerase II and androgen receptor (AR). This led to the identification of several transcriptional enhancers, which were verified using reporter assays. Two enhancers in one risk region were occupied by AR and responded to androgen treatment; one contained a single nucleotide polymorphism (rs11986220) that resides within a FoxA1 binding site, with the prostate cancer risk allele facilitating both stronger FoxA1 binding and stronger androgen responsiveness. The study reported here exemplifies an approach that may be applied to any risk-associated allele in non-protein coding regions as it emerges from genome-wide association studies to better understand the genetic predisposition of complex diseases.

Cell Line

Chromosomes, Human, Pair 8 - genetics

Chromosomes, Human, Pair 8 - metabolism

Genome-Wide Association Study

Enhancer Elements, Genetic

Neoplasms - genetics

Humans

Details

Title: Subtitle: Functional enhancers at the gene-poor 8q24 cancer-linked locus
Creators: Li Jia - USC/Norris Cancer Center, Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA
Gilad Landan
Mark Pomerantz
Rami Jaschek
Paula Herman
David Reich
Chunli Yan
Omar Khalid
Phil Kantoff
William Oh
J Robert Manak
Benjamin P Berman
Brian E Henderson
Baruch Frenkel
Christopher A Haiman
Matthew Freedman
Amos Tanay - Weizmann Institute of Science
Gerhard A Coetzee
Resource Type: Journal article
Publication Details: PLoS genetics, Vol.5(8), pp.e1000597-e1000597
DOI: 10.1371/journal.pgen.1000597
PMID: 19680443
PMCID: PMC2717370
NLM abbreviation: PLoS Genet
ISSN: 1553-7390
eISSN: 1553-7404
Publisher: United States
Grant note: R01 CA129435 / NCI NIH HHS\nR01 CA109147 / NCI NIH HHS\nP50 CA090381 / NCI NIH HHS\n5 P50 CA90381 / NCI NIH HHS
Language: English
Date published: 08/2009
Academic Unit: Stead Family Department of Pediatrics; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9983991960302771

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