Top2a promotes the development of social behavior via PRC2 and H3K27me3.
Top2a promotes the development of social behavior via PRC2 and H3K27me3.
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DOI：
10.1126/sciadv.abm7069
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发表时间：
2022-11-25
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
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关于社会性的胚胎发展，几乎没有理解。与自闭症的核心症状相关的行为。复合物2（PRC2），用于H3K27三甲基化的调节络合物（H3K27me3）。一种进化的途径，通过PRC2和H3K27ME3促进社会行为的发展。
TOP2A-PRC2-H3K27ME3途径调节自闭症风险基因的表达并驱动社会性的发展。
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. A Top2a-PRC2-H3K27me3 pathway regulates expression of autism risk genes and drives development of sociality.
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DOI：
10.1093/bioinformatics/btv301
发表时间：
2015-09-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Gutiérrez-Sacristán A;Grosdidier S;Valverde O;Torrens M;Bravo À;Piñero J;Sanz F;Furlong LI
通讯作者：
Furlong LI
影响因子：
30.8
作者：
Coe, Bradley P.;Stessman, Holly A. F.;Eichler, Evan E.
通讯作者：
Eichler, Evan E.
影响因子：
5.3
作者：
Dovey, Michael;Patton, E. Elizabeth;Zon, Leonard I.
通讯作者：
Zon, Leonard I.
影响因子：
30.8
作者：
Allen, Nicole C.;Bagade, Sachin;Bertram, Lars
通讯作者：
Bertram, Lars
影响因子：
5.2
作者：
Fehr, Markus;Pahlke, Gudrun;Marko, Doris
通讯作者：
Marko, Doris