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Series GSE43899 Query DataSets for GSE43899
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
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.
 
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.
 
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 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
City Carrboro
State/province NC
ZIP/Postal code 27510
Country USA
 
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]
Samples (56)
GSM1179388 1000nM_Topotecan
GSM1179389 150nM_Topotecan
GSM1179390 300nM_Topotecan_1
This SubSeries is part of SuperSeries:
GSE43900 Co-ordinate inhibition of autism candidate genes by topoisomerase inhibitors
Relations
BioProject PRJNA188087

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE43899_RAW.tar 251.5 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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