克服H4K20me3表观遗传障碍提高了小鼠体细胞核转移重编程效率
Zhihui Liu1, Weiguo Wang1, Yuhan Xia1
1Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
Cell proliferation
|June 16, 2023
概括
在受精和克隆胚胎之间,Histone H4K20me3的表观遗传标记有所不同. 在克隆胚胎中减少H4K20me3可以改善发育和重编程,揭示了它在细胞可塑性中的作用.
科学领域:
- 表观遗传学和发育生物学
- 生殖生物学 生殖生物学
- 基因组学和基因调控 基因组学和基因调控
背景情况:
- 表观遗传重编程对于受精和体细胞核转移 (NT) 后的发育至关重要.
- 基因组H4K20me3是一种压制性表观遗传标记,与异染色的形成和细胞可塑性有关.
- 了解H4K20me3的动态是提高克隆效率和理解发育过程的关键.
研究的目的:
- 在小鼠受精和NT重编程过程中描述H4K20me3的表观遗传修饰模式.
- 调查H4K20me3在发展能力中的作用,并确定其基础的监管机制.
- 评估操纵H4K20me3的潜力,以提高NT重编程结果.
主要方法:
- 免疫光染色可视化H4K20me3分布在受精,NT和帕氏遗传激活 (PA) 胚胎中.
- 在不同植入前阶段对H4K20me3强度的定量分析.
- 对H4K20甲基转移酶Suv4-20h2的RNA表达分析和NT胚胎中的敲除实验.
- 在 Suv4-20h2 敲除后评估胚胎细胞发育和全日期克隆效率.
主要成果:
- 在受精胚胎和NT/PA胚胎之间,H4K20me3模式存在显著差异,受精胚胎的强度较低.
- 与NT胚胎相比,受精胚胎的Suv4-20h2表达率较低,与H4K20me3水平相关.
- 在NT胚胎中,Suv4-20h2的淘汰使H4K20me3模式正常化,改善了胚胎细胞的发育 (30.5%对11.1%),并提高了克隆效率 (5.9%对0.8%).
- Suv4-20h2 knockdown 在NT胚胎中调节了关键重编程和胚胎基因组激活因子.
结论:
- 在小鼠中,H4K20me3作为表观遗传障碍,有效地对体细胞核转移重编程.
- 异常的H4K20me3调控有助于NT和PA胚胎的发育缺陷.
- 针对Suv4-20h2和H4K20me3提供了一个有希望的策略,以提高克隆效率,并了解细胞可塑性的表观遗传控制.
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