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| Status |
Public on Mar 20, 2014 |
| Title |
Transcriptional effects of CSB and the CSB-PGBD3 fusion protein in CSB-null UVSS1KO cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Cockayne syndrome is a segmental progeria most often caused by mutations in the CSB gene encoding a SWI/SNF-like ATPase required for transcription-coupled DNA repair (TCR). Over 43 Mya before marmosets diverged from humans, a piggyBac3 (PGBD3) transposable element integrated into intron 5 of the CSB gene. As a result, primate CSB genes now generate both CSB protein and a conserved CSB-PGBD3 fusion protein in which the first 5 exons of CSB are alternatively spliced to the PGBD3 transposase. We show by microarray analysis that expression of the fusion protein alone in CSB-null UV-sensitive syndrome cells (UVSS1KO) cells induces an interferon-like response that resembles both the innate antiviral response and the prolonged interferon response normally maintained by unphosphorylated STAT1 (U-STAT1); moreover, as might be expected based on conservation of the fusion protein, this potentially cytotoxic interferon-like response is largely reversed by coexpression of functional CSB protein. Interestingly, expression of CSB and the CSB-PGBD3 fusion protein together, but neither alone, upregulates the insulin growth factor binding protein IGFBP5 and downregulates IGFBP7, suggesting that the fusion protein may also confer a metabolic advantage, perhaps in the presence of DNA damage. Finally, we show that the fusion protein binds in vitro to members of a dispersed family of 900 internally deleted piggyBac elements known as MER85s, providing a potential mechanism by which the fusion protein could exert widespread effects on gene expression. Our data suggest that the CSB-PGBD3 fusion protein is important in both health and disease, and could play a role in Cockayne syndrome.
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| Overall design |
12 samples total; 4 gene expression conditions in triplicate; 1 condition is a tag-only negative control
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| Contributor(s) |
Bailey AD, Gray LT, Weiner AM |
| Citation(s) |
22483866 |
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| Submission date |
Mar 20, 2014 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Lucas T Gray |
| E-mail(s) |
[email protected]
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| Organization name |
Allen Institute for Brain Science
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| Department |
Molecular Genetics
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| Lab |
Tasic
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| Street address |
615 Westlake Ave N
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| 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 (12)
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| GSM1354412 |
Stable FLAG-HA expression, biological replicate 1 |
| GSM1354413 |
Stable FLAG-HA expression, biological replicate 2 |
| GSM1354414 |
Stable FLAG-HA expression, biological replicate 3 |
| GSM1354415 |
Stable FLAG-HA-CSB expression, biological replicate 1 |
| GSM1354416 |
Stable FLAG-HA-CSB expression, biological replicate 2 |
| GSM1354417 |
Stable FLAG-HA-CSB expression, biological replicate 3 |
| GSM1354418 |
Stable FLAG-HA-CSB-PGBD3 expression, biological replicate 1 |
| GSM1354419 |
Stable FLAG-HA-CSB-PGBD3 expression, biological replicate 2 |
| GSM1354420 |
Stable FLAG-HA-CSB-PGBD3 expression, biological replicate 3 |
| GSM1354421 |
Stable FLAG-HA-CSB and FLAG-CSB-PGBD3 co-expression, biological replicate 1 |
| GSM1354422 |
Stable FLAG-HA-CSB and FLAG-CSB-PGBD3 co-expression, biological replicate 2 |
| GSM1354423 |
Stable FLAG-HA-CSB and FLAG-CSB-PGBD3 co-expression, biological replicate 3 |
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| Relations |
| BioProject |
PRJNA242304 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE56049_RAW.tar |
59.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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