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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Functional enhancers at the gene-poor 8q24 cancer-linked locus
PLoS Genetics, Volume 5, No. 8, Article e1000597, Year 2009
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Description
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 nonprotein coding regions as it emerges from genome-wide association studies to better understand the genetic predisposition of complex diseases. © 2009 Jia et al.
Authors & Co-Authors
Pomerantz, Mark M.
United States, Boston
Dana-farber Cancer Institute
Reich, David E.
United States, Boston
Harvard Medical School
Kantoff, Philip W.
United States, Boston
Dana-farber Cancer Institute
Oh, William K.
United States, Boston
Dana-farber Cancer Institute
Manak, John Robert
United States, Iowa City
University of Iowa
Henderson, Brian E.
United States, Los Angeles
University of Southern California
Haiman, Christopher A.
United States, Los Angeles
University of Southern California
Freedman, Matthew Lee
United States, Los Angeles
University of Southern California
United States, Cambridge
Massachusetts Institute of Technology
Coetzee, Gerhard A.
United States, Los Angeles
University of Southern California
Statistics
Citations: 201
Authors: 9
Affiliations: 6
Identifiers
Doi:
10.1371/journal.pgen.1000597
ISSN:
15537404
Research Areas
Cancer
Genetics And Genomics