在口腔上皮质中以2-依赖的甲基化促进了二次 palatogenesis
Bo Sun1, Kurt Reynolds1, Subbroto Kumar Saha1
1Institute for Pediatric Regenerative Medicine of Shriners Hospital for Children-Northern California & Department of Biochemistry and Molecular Medicine, School of Medicine, University of California at Davis, Sacramento, California, USA.
Birth defects research
|July 12, 2023
概括
表观遗传调节器Ezh2对于适当的 palatal 发育至关重要. 在口腔上皮质中缺少它会导致嘴巴裂口,因为它会破坏细胞循环控制和小鼠的架子升高.
科学领域:
- 发展生物学 发展生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 遗传学 是一个遗传学.
背景情况:
- 除了遗传和环境因素之外,表观遗传修饰也越来越多地与面部或面部发育和裂有关.
- 增强ZesteHomolog 2 (Ezh2) 是Polycomb抑制综合体的一个关键组成部分,通过基因组胺甲基化调节基因表达.
- 之前还没有确定Ezh2在面腔裂中的特定作用.
研究的目的:
- 阐明二次 palatogenesis 期间 Ezh2-介导甲基化的上皮功能.
- 为了研究Ezh2损失对基因表达和发育口腔中的细胞过程的影响.
主要方法:
- 使用条件基因向来删除小鼠胚胎口腔表皮中的Ezh2.
- 单细胞RNA测序,免疫光和RT-qPCR被用来分析突变口腔中的基因表达.
- 进行了Ezh1和Ezh2的双淘汰分析,以评估潜在的协同作用.
主要成果:
- 在口腔表皮上有条件的Ezh2无活化导致了部分透的裂口 palatal 现型.
- 发现Ezh1对于口腔和面部发育是不可或缺的,并且与Ezh2.2没有产生协同效应.
- 分析显示,Ezh2突变 palatal 表皮质中细胞周期调节者的调节失调,扰乱了 palatogenesis.
结论:
- 依赖EZh2的素H3K27甲基化抑制了Cdkn1a的表达,在 palatal 发育过程中促进了上皮细胞的增殖.
- 这种表观遗传调节因Ezh2丧失而受到破坏,可能会损害 palatal shelf 的运动和融合,导致 palatal cleft.
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