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Title: Co-ordinate inhibiton of autism candidate genes by topoisomerase inhibitors [array]      
dateReleased:
08-30-2013
description:
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. 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.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-43899
refinement:
raw
alternateIdentifiers:
43899
keywords:
functional genomics
dateModified:
09-26-2013
availability:
available
types:
gene expression
name:
Mus musculus
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-43899/E-GEOD-43899.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-43899/E-GEOD-43899.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43899
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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