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Updated: Aug 20, 2025

A Method to Study de novo Formation of Chromatin Domains
Published on: August 23, 2019
Top2a promotes the development of social behavior via PRC2 and H3K27me3
Yijie Geng1, Tejia Zhang1, Ivy G Alonzo1
1Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT 84112, USA.
Abstract:
Little is understood about the embryonic development of sociality. We screened 1120 known drugs and found that embryonic inhibition of topoisomerase IIα (Top2a) resulted in lasting social deficits in zebrafish. In mice, prenatal Top2 inhibition caused defects in social interaction and communication, which are behaviors that relate to core symptoms of autism. Mutation of Top2a in zebrafish caused down-regulation of a set of genes highly enriched for genes associated with autism in humans. Both the Top2a-regulated and autism-associated gene sets have binding sites for polycomb repressive complex 2 (PRC2), a regulatory complex responsible for H3K27 trimethylation (H3K27me3). Moreover, both gene sets are highly enriched for H3K27me3. Inhibition of the PRC2 component Ezh2 rescued social deficits caused by Top2 inhibition. Therefore, Top2a is a key component of an evolutionarily conserved pathway that promotes the development of social behavior through PRC2 and H3K27me3.
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