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| Status |
Public on May 17, 2007 |
| Title |
Modulating hypoxia-inducible transcription by disrupting the HIF-1-DNA interface |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Transcription mediated by hypoxia inducible factor (HIF-1) contributes to tumor angiogenesis and metastasis but is also involved in the activation of cell-death pathways and normal physiological processes. Given the complexity of HIF-1 signaling it could be advantageous to target a subset of HIF-1 effectors rather than the entire pathway. We compared the genome-wide effects of three molecules that each interfere with the HIF-1-DNA interaction: a polyamide targeted to the hypoxia response element (HRE), siRNA targeted to HIF-1α, and echinomycin, a DNA binding natural product with a similar but less specific sequence preference to the polyamide. The polyamide affects a subset of hypoxia-induced genes that are consistent with the binding site preferences of the polyamide. For comparison, siRNA targeted to HIF-1α and echinomycin each affect the expression of nearly every gene induced by hypoxia. Remarkably, the total number of genes affected by either polyamide or HIF-1α siRNA over a range of thresholds is comparable. The data shows how polyamides can be used to affect a subset of a pathway regulated by a transcription factor. In addition, this study offers a unique comparison of three complementary approaches towards exogenous control of endogenous gene expression.
Keywords: Gene expression changes in cultured U251 cells after DFO-stimulation and various treatment conditions
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| Overall design |
Hypoxia-mimetic DFO (deferoxamine)-stimulated U251 cells that were treated with polyamide 1, HIF-1a siRNA, and echinomycin were compared to control cells that were also DFO-stimulated. Cells not stimulated with DFO were also compared to the DFO-stimulated controls. Three biological replicates were included for each treatment/condition.
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| Contributor(s) |
Dervan PB, Nickols NG, Jacobs CS, Farkas ME |
| Citation(s) |
17708671 |
| |
| Submission date |
May 17, 2007 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Peter Dervan |
| Organization name |
California Institute of Technology
|
| Street address |
1200 East California Blvd
|
| City |
Pasadena |
| State/province |
CA |
| ZIP/Postal code |
91125 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA100075 |
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