乳酸盐通过哺乳动物的H3K18乳化来调节主要的胚胎基因组激活
Jingyu Li1, Weibo Hou2, Qi Zhao2
1Chongqing Key Laboratory of Human Embryo Engineering, Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, Chongqing 400010, China.
National science review
|February 8, 2024
概括
乳酸对哺乳动物胚胎发育至关重要,特别是对于主要的胚胎基因组激活 (ZGA). 这项研究揭示了乳酸盐.
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.
- 代谢过程中的代谢.
背景情况:
- 在哺乳动物植入前胚胎中观察到高乳酸水平.
- 乳酸在早期胚胎发育中的确切作用仍然在很大程度上是未知的.
研究的目的:
- 为了研究乳酸在哺乳动物植入前发育过程中的功能.
- 为了探索乳酸,基因组修饰和胚胎基因组激活 (ZGA) 之间的联系.
主要方法:
- 在小鼠胚胎中抑制乳酸生产和吸收.
- 通过ChIP-seq.对基因素修饰H3K18lac丰富的分析.
- 过度表达H3K18R突变和Lac-CoA添加用于救援实验.
- 人类和小鼠胚胎的比较分析.
主要成果:
- 乳酸在人类和小鼠的主要ZGA期间在胚胎核中得到丰富.
- 乳酸抑制会导致发育停止,ZGA失败和H3K18lac的丧失.
- H3K18lac富含ZGA基因促进体,与基因表达相关.
- 这些效应在添加Lac-CoA或H3K18R突变时是可逆的.
结论:
- 乳酸盐及其衍生基因组修饰H3K18lac在主要ZGA中发挥着关键作用.
- 一个涉及乳酸的保存代谢机制是哺乳动物植入前发育的基础.
- H3K18lac作为ZGA基因激活的关键表观遗传调节剂.
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