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Accession IconGSE43899

Co-ordinate inhibiton of autism candidate genes by topoisomerase inhibitors [array]

Organism Icon Mus musculus
Sample Icon 48 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Gene 2.1 ST Array (mogene21st), Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Gene 1.1 ST Array (mogene11st)

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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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