Enzymes Key to Expression of Genes Linked to Autism
(HealthDay News) – A class of enzymes called topoisomerases is important for the expression of very long genes, which are common among genes linked to autism spectrum disorder (ASD), according to a study published online Aug. 28 in Nature.
Building on the observation that topoisomerases are mutated in some cases of ASD and previous results showing that topoisomerase inhibitors reduce the expression of an extremely long (>1 megabase) imprinted gene in neurons, Ian F. King, PhD, from the University of North Carolina at Chapel Hill, and colleagues investigated whether topoisomerase inhibitors reduced the expression of other long genes.
The researchers found that topotecan, an inhibitor of topoisomerase 1, reduced the expression of extremely long genes in neurons, including nearly all >200 kilobases long. Similarly, knockdown of Top1 or Top2b in neurons also reduced the expression of long genes. Further investigation showed that transcription elongation was impaired. Reduced gene expression was observed for many candidate ASD genes, which are often exceptionally long.
"Our findings suggest that chemicals and genetic mutations that impair topoisomerases could commonly contribute to ASD and other neurodevelopmental disorders," King and colleagues conclude.