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| Status |
Public on Aug 02, 2012 |
| Title |
SIN3A-regulated LIF-responsive genes in MCF7 cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Tyrosine phosphorylation is a hallmark for activation of Signal Transducer and Activator of Transcription (STAT) proteins, but their transcriptional activity also depends on other secondary modifications. Type I interferons (IFNs) can activate both the ISGF3 (STAT1:STAT2:IRF9) complex and STAT3, but with cell-specific, selective triggering of only the ISGF3 transcriptional program. Following a genome-wide RNAi screen, we identified the Sin3a complex as an important mediator of this STAT3 transcriptional repression. Sin3a directly interacts with the DNA-binding domain of STAT3 and alters its acetylation status. SIN3A silencing enhances recruitment of STAT3 and enhanceosome components to the SOCS3 promoter, resulting in histone hyperacetylation and enhanced transcription. Conversely, Sin3a is required for ISGF3-dependent gene transcription and for an efficient IFN-mediated antiviral protection against Influenza A and hepatitis C viruses. The Sin3a complex therefore acts as a context-dependent STAT1/3 transcriptional switch.
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| Overall design |
MCF7 cells were transfected with 50nM Renilla luciferase (control) or SIN3A-specific siRNA. 72h later, cells were cultured for 4h in absence of FCS and left non-stimulated or stimulated with LIF (10ng/ml, 1h). Total RNA was extracted. For each of the 4 conditions, 3 biological replicates were included. Nevertheless, one sample (SIN3A_siRNA_LIF1h_rep3) was discarded. In total 11 samples were analyzed.
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| Contributor(s) |
Icardi L, Mori R, Gesellchen V, Eyckerman S, De Cauwer L, Verhelst J, Vercauteren K, Saelens X, Meuleman P, Leroux-Roels G, De Bosscher K, Boutros M, Tavernier J |
| Citation(s) |
22783022 |
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| Submission date |
Feb 10, 2012 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Rekin's Janky |
| E-mail(s) |
Nucleomics.Bioinformatics@vib.be
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| Organization name |
VIB
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| Department |
Nucleomics Core
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| Street address |
Herestraat 49 Box 816
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| City |
Leuven |
| ZIP/Postal code |
B-3000 |
| Country |
Belgium |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA152031 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35696_RAW.tar |
51.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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