Lengthy genes cut short

摘要

Topoisomerases, enzymes involved in DNA winding, are expressed throughout the brain and mutated versions have been found in people with autism spectrum disorders (ASD). Mark Zylka and colleagues show that reducing topoisomerase activity selectively reduces the expression of long genes in mouse and human neurons by impairing transcription elongation. Many ASD candidate genes, including Cntnap2, Nrxnl and Cntn4y are exceptionally long and the authors confirm that expression of several ASD candidate genes is reduced by topoisomerase inhibition. These findings suggest that chemicals and genetic mutations that impair topoisomerases could contribute to ASD and other neurodevelopmental disorders.