在体内,FoxP3形成头对头二极体,并在相邻的微卫星上稳定其多元化
Fangwei Leng1,2,3,4, Ryan Clark1,2,4, Wenxiang Zhang1,2,5
1Howard Hughes Medical Institute and Program in Cellular and Molecular Medicine, Boston Children's Hospital, MA 02115, USA.
bioRxiv : the preprint server for biology
|September 26, 2025
概括
福克斯P3 (框P3) 使用两个DNA结合方法来调节Tregs中的基因. 它可以形成二聚体或多聚体,增强其在染色质循环中的作用.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 福克斯P3是调控T细胞 (Tregs) 的主调节器.
- 福克斯P3使用不同的DNA结合模式:TnG重复的多元化和反向重复叉形图案 (IR-FKHM) 的头对头 (H-H) 二元化.
- 之前缺乏FoxP3 H-H二元化的体内证据.
研究的目的:
- 为了识别驱动FoxP3 H-H二元化的新型DNA动机.
- 在Tregs.中对FoxP3结合模式进行全基因组分析.
- 了解FoxP3的DNA结合模式和染色质结构之间的相互作用.
主要方法:
- 无偏向的拉下序列来识别FoxP3结合动机.
- 对Tregs.中的FoxP3结合的全基因组分析.
- 对FoxP3的 ортолог进行比较分析.
主要成果:
- 发现了促进FoxP3 H-H二元化的放松图案.
- 证明FoxP3将基因组DNA作为Tregs中的H-H二元和多元结合在一起.
- 证据表明,H-H二元化可以在相邻的TnG重复上启动和稳定多元化,特别是低于最佳的重复.
- 鉴定H-H二元化作为FoxP3特异性特征,在其他FoxP成员中不存在,由于其分离的辅助循环.
结论:
- 在体内,FoxP3采用双模式DNA结合策略 (H-H二元化和多元化).
- 这种双模式结合扩大了FoxP3的序列识别,并增强了其在染色质循环中的功能.
- H-H二元化是FoxP3的独一无二的特征,有助于其专门的调节作用.
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