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| Status |
Public on Dec 19, 2009 |
| Title |
Functional enhancers at the gene-poor 8q24 cancer-linked locus |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by genome tiling array
Genome binding/occupancy profiling by genome tiling array
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| Summary |
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.
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| Overall design |
20 Normal Prostate cDNA samples (no replicates), 4 cell line cDNA samples (each cell line in duplicate), 4 cell line Acetylated H3 ChIP (each line in duplicate), 2 cell line various histone modification and protein ChIPs (6 Abs LNCaP, 5 Abs PC3, each in duplicate). All samples were hybridized with matching genomic DNA as reference.
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| Contributor(s) |
Jia L, Landan G, Pomerantz M, Jaschek R, Herman P, Reich D, Yan C, Khalid O, Kantoff P, Oh W, Manak JR, Berman BP, Henderson BE, Frenkel B, Haiman CA, Freedman M, Tanay A, Coetzee GA |
| Citation(s) |
19680443 |
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| Submission date |
Dec 18, 2009 |
| Last update date |
Mar 21, 2012 |
| Contact name |
Gilad Landan |
| E-mail(s) |
gilad.landan@weizmann.ac.il
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| Organization name |
Weizmann Institute of Science
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| Department |
Applied Math & Computer Science, Molecular Cell Biology
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| Lab |
Amos Tanay, Varda Rotter
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| Street address |
PO Box 26
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| City |
Rehovot |
| ZIP/Postal code |
76100 |
| Country |
Israel |
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| Platforms (1) |
| GPL9816 |
8q24 Nimblegen Homo sapiens 385K custom tiling array |
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| Samples (20)
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| GSM487614 |
LNCaP cDNA |
| GSM487615 |
PC3 cDNA |
| GSM487616 |
MCF7 Acetylation Histone 3 ChIP |
| GSM487617 |
HCT116 Acetylation Histone 3 ChIP |
| GSM487618 |
LNCaP Acetylation Histone 3 ChIP |
| GSM487619 |
PC3 ChIP Acetylation Histone 3 ChIP |
| GSM487620 |
LNCaP RNA Polymerase II ChIP |
| GSM487621 |
LNCaP Histone 3 Lysine 36 Trimethylation ChIP |
| GSM487622 |
LNCaP Androgen Receptor ChIP |
| GSM487623 |
LNCaP Histone 3 Lysine 4 Monomethylation ChIP |
| GSM487624 |
LNCaP Histone 3 Lysine 4 Trimethylation ChIP |
| GSM487625 |
LNCaP Histone 3 Lysine 27 Trimethylation ChIP |
| GSM487626 |
PC3 RNA Polymerase II ChIP |
| GSM487627 |
PC3 Histone 3 Lysine 36 Trimethylation ChIP |
| GSM487628 |
PC3 Histone 3 Lysine 4 Monomethylation ChIP |
| GSM487629 |
PC3 Histone 3 Lysine 4 Trimethylation ChIP |
| GSM487630 |
PC3 Histone 3 Lysine 27 Trimethylation ChIP |
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| Relations |
| BioProject |
PRJNA122405 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE19561_RAW.tar |
703.2 Mb |
(http)(custom) |
TAR (of PAIR) |
| Processed data included within Sample table |
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