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| Status |
Public on Sep 18, 2013 |
| Title |
Genes induced by IFN-beta, IFN-gamma or unphosphoraylted STAT1 in human fibroblasts |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
A single high dose of IFNβ activates powerful cellular responses in which many antiviral, pro-apoptotic, and anti-proliferative proteins are highly expressed. Since some of these proteins are deleterious, cells down-regulate this initial response rapidly. However, the expression of many antiviral proteins that do no harm is sustained, prolonging a substantial part of the initial antiviral response for days and also providing resistance to DNA damage. While the transcription factor ISGF3 (IRF9 and tyrosine-phosphorylated STATs 1 and 2) drives the first rapid response phase, the related factor un-phosphorylated ISGF3 (U-ISGF3), formed by IFNβ-induced high levels of IRF9 and STATs 1 and 2 without tyrosine phosphorylation, drives the second prolonged response. The U-ISGF3-induced antiviral genes that show prolonged expression are driven by distinct interferon stimulated response elements (ISREs). Continuous exposure of cells to a low level of IFNβ, often seen in cancers, leads to steady-state increased expression of only the U-ISGF3-dependent proteins, with no sustained increase of other IFNβ-induced proteins, and to constitutive resistance to DNA damage.
We classified genes into U-ISGF3-induced genes and classical ISGF3-induced genes using microarray data. We identified 150 genes that are up-regulated by IFNβ after 6 h. Among these IFNβ-induced genes, only 29 (20%) were induced by the up-regulation of Y701F-STAT1, indicating that these are induced by U-ISGF3. Among the remaining 121 IFNβ-induced genes (150 minus 29), 73 are induced by IFNγ as well as IFNβ, and 48 are induced only by IFNβ.
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| Overall design |
Total 5 RNA samples were analyzed in duplicate on microarray chips. Untreated cells and empty vector-transfected cells were the control of IFN treated cells and Y701F-STAT1-transfected cells, respectively.
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| Contributor(s) |
Cheon H, Stark GR |
| Citation(s) |
24065129 |
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| Submission date |
Sep 17, 2013 |
| Last update date |
Mar 14, 2014 |
| Contact name |
HyeonJoo Cheon |
| E-mail(s) |
[email protected]
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| Phone |
216-445-9769
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| Organization name |
Cleveland Clinic
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| Department |
Molecular Genetics
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| Lab |
NE2-252
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| Street address |
9500 Euclid Ave
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| City |
Cleveland |
| State/province |
OH |
| ZIP/Postal code |
44122 |
| Country |
USA |
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| Platforms (1) |
| GPL6104 |
Illumina humanRef-8 v2.0 expression beadchip |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA219422 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE50954_RAW.tar |
3.4 Mb |
(http)(custom) |
TAR |
| GSE50954_non-normalized.txt.gz |
888.8 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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