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| Status |
Public on Aug 30, 2013 |
| Title |
Co-ordinate inhibiton of autism candidate genes by topoisomerase inhibitors [array] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Topoisomerases are necessary for the expression of neurodevelopmental genes, and are mutated in some patients with autism spectrum disorder (ASD). We have studied the effects of inhibitors of Topoisomerase 1 (Top1) and Topoisomerase 2 (Top2) enzymes on mouse cortical neurons. We find that topoisomerases selectively inhibit long genes (>100kb), with little effect on all other gene expression. Using ChIPseq against RNA Polymerase II (Pol2) we show that the Top1 inhibitor topotecan blocks transcriptional elongation of long genes specifically. Many of the genes inhibited by topotecan are candidate ASD genes, leading us to propose that topoisomerase inhibition might contribute to ASD pathology.
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| Overall design |
9 experiments, gene expression measured by Affymetrix microarray.
1) cultured mouse cortical neurons treated with 300nM topotecan vs vehicle-treated controls
2) cultured mouse neurons treated with 1uM topotecan vs vehicle-treated controls
3) cultured mouse cortical neurons treated with 3uM ICRF-193 vs vehicle-treated controls.
4) cultured mouse cortical neurons treated with 10 uM irinotecan vs vehicle-treated controls.
5) cultured mouse cortical neurons treated with 3-1000 nM topotecan vs vehicle treated controls
6) cultured mouse cortical neurons treated with lentivirus expressing shRNA against Top1 and Top2b vs scrambled shRNA controls
7) cultured mouse cortical neurons treated with DRB vs vehicle-treated controls
8) cultured mouse cortical neurons treated with hydrogen peroxide or paraquat vs vehicle-treated controls
9) cultured mouse cortical neurons treated with topotecan with or without subsequent drug washout, vs vehicle-treated controls.
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| Contributor(s) |
King IF, Yandava C |
| Citation(s) |
23995680 |
| Submission date |
Jan 30, 2013 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Chandri Yandava |
| E-mail(s) |
yandava@email.unc.edu
|
| Organization name |
University of North Carolina at Chapel Hill
|
| Department |
Carolina Institute for Developmental Disabilities
|
| Street address |
101 Renee Lynne Court
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| City |
Carrboro |
| State/province |
NC |
| ZIP/Postal code |
27510 |
| Country |
USA |
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| Platforms (3) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
| GPL11533 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] |
| GPL17400 |
[MoGene-2_1-st] Affymetrix Mouse Gene 2.1 ST Array [transcript (gene) version] |
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| Samples (56)
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| This SubSeries is part of SuperSeries: |
| GSE43900 |
Co-ordinate inhibition of autism candidate genes by topoisomerase inhibitors |
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| Relations |
| BioProject |
PRJNA188087 |
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