Chromosomes (image) University of North Carolina Health Care Caption Angelman syndrome is a severe neurodevelopmental disorder caused by mutation or deletion of the maternally inherited copy of Ube3a (blackened region of the chromosomes). The paternally inherited copy of Ube3a is intact but epigenetically silenced in neurons (grey neuron, green chromosomal region). A high‑content screen with mouse primary cortical neurons identified several topoisomerase I and II inhibitors (white flurries covering pink neuron) that unsilence the paternal copy of Ube3a. This study highlights a role for topoisomerase enzymes in epigenetic gene regulation and suggests a novel approach for restoring Ube3a function in patients with Angelman syndrome. Credit Illustration by Janet Iwasa. Usage Restrictions None Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.