在小鼠植入前胚胎中扰乱核糖化,减缓胚胎发育速度
Sara Formichetti1,2, Joana B Serrano1, Urvashi Chitnavis1
1Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory (EMBL) Rome, Monterotondo 00015, Italy.
概括
在早期胚胎中去除核O-GlcNAc (O-链接的N-乙糖胺) 并没有影响基因组激活,但通过影响蛋白质合成和细胞分裂,将糖化与胚胎速度联系起来,延迟了发育.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 生物化学 生化学
背景情况:
- 细胞内蛋白质糖化,O-GlcNAc,是一种在数千种蛋白质上发现的动态翻译后修饰.
- O-GlcNAc被O-GlcNAc转移酶催化,对于哺乳动物的早期发育至关重要.
- 在胚胎发育中O-GlcNAc的作用和胚胎O-GlcNAc蛋白质仍然在很大程度上未被描述.
研究的目的:
- 研究早期哺乳动物胚胎发育期间核O-GlcNAc的调节功能.
- 描述O-GlcNAc枯竭对胚胎基因组激活 (EGA) 和随后的发育事件的影响.
主要方法:
- 在植入前胚胎中开发了一种酶去除核O-GlcNAc的策略.
- 评估了O-GlcNAc耗尽对EGA,转录形状和细胞周期调节的影响.
- 从体型上评估的发育进展,从切割阶段到植入后.
主要成果:
- 将核O-GlcNAc耗尽到无法检测的水平并没有影响EGA.
- 降低的O-GlcNAc水平抑制了翻译机制的上调.
- O-GlcNAc的耗尽引发了螺旋检查点反应,并导致发育延迟.
结论:
- 核O-GlcNAc对EGA并不重要,但在调节转化机制方面起着至关重要的作用.
- 核O-GlcNAc的去除导致发育延迟,突出了其在控制早期胚胎发育速度方面的重要性.
- 建立了核蛋白糖化和胚胎发育时间之间的直接联系.
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