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| Status |
Public on Nov 29, 2011 |
| Title |
Genome-wide Runx2 occupancy in prostate cancer cells suggests a role in regulating secretion. |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Runx2 is a metastatic transcription factor (TF) increasingly expressed during prostate cancer (PCa) progression. Using PCa cells conditionally expressing Runx2, we previously identified Runx2-regulated genes with known roles in epithelial-mesenchymal transition, invasiveness, angiogenesis, extracellular matrix proteolysis and osteolysis. To map Runx2-occupied regions (R2ORs) in PCa cells, we first analyzed regions predicted to bind Runx2 based on the expression data, and found that recruitment to sites upstream of the KLK2 and CSF2 genes was cyclical over time. Genome-wide ChIP-seq analysis at a time of maximum occupancy at these sites revealed 1,603 high-confidence R2ORs, enriched with cognate motifs for RUNX, GATA and ETS TFs. The R2ORs were distributed with little regard to annotated transcription start sites (TSSs), mainly in introns and intergenic regions. Runx2-upregulated genes, however, displayed enrichment for R2ORs within 40 kb of their TSSs. The main annotated functions enriched in 98 Runx2-upregulated genes with nearby R2ORs were related to invasiveness and membrane trafficking/secretion. Indeed, using SDS-PAGE, mass spectrometry and western analyses, we show that Runx2 enhances secretion of several proteins, including fatty acid synthase and metastasis-associated laminins. Thus, combined analysis of Runx2’s transcriptome and genomic occupancy in PCa cells lead to defining its novel role in regulating protein secretion.
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| Overall design |
Examination of Runx2 in Prostate Cancer cells
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| Contributor(s) |
Little GH, Noushmehr H, Baniwal SK, Berman BP, Coetzee GA, Frenkel B |
| Citation(s) |
22187159 |
| Submission date |
Nov 22, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Houtan Noushmehr |
| Phone |
310-570-2362
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| Organization name |
Henry Ford Health System
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| Street address |
2799 W. Grand Blvd
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| City |
Detroit |
| State/province |
MI |
| ZIP/Postal code |
48202 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (2) |
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| Relations |
| SRA |
SRP009428 |
| BioProject |
PRJNA148325 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33889_RAW.tar |
30.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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