PUBLICATION
Top2a promotes the development of social behavior via PRC2 and H3K27me3
- Authors
- Geng, Y., Zhang, T., Alonzo, I.G., Godar, S.C., Yates, C., Pluimer, B.R., Harrison, D.L., Nath, A.K., Yeh, J.J., Drummond, I.A., Bortolato, M., Peterson, R.T.
- ID
- ZDB-PUB-221124-6
- Date
- 2022
- Source
- Science advances 8: eabm7069eabm7069 (Journal)
- Registered Authors
- Nath, Anjali, Peterson, Randall, Yeh, Jing-Ruey (Joanna)
- Keywords
- none
- Datasets
- GEO:GSE181730
- MeSH Terms
- none
- PubMed
- 36417527 Full text @ Sci Adv
Citation
Geng, Y., Zhang, T., Alonzo, I.G., Godar, S.C., Yates, C., Pluimer, B.R., Harrison, D.L., Nath, A.K., Yeh, J.J., Drummond, I.A., Bortolato, M., Peterson, R.T. (2022) Top2a promotes the development of social behavior via PRC2 and H3K27me3. Science advances. 8:eabm7069eabm7069.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping