阅读器YTHDC1静止反转移体并保护ES细胞的身份
Jiadong Liu1,2,3, Mingwei Gao1,2,3, Jiangping He4
1CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Nature
|March 4, 2021
概括
通过抑制逆转移体,RNA阅读器YTHDC1维持小鼠胚胎干细胞. 它的缺失会通过表观遗传变化引发重编程到类似2C的状态.
科学领域:
- 表观遗传学和基因调控
- 哺乳动物胚胎发育
- 核糖核酸生物学
背景情况:
- N6-甲基氨酸 (m6A) 是生物过程中关键的RNA修饰物.
- m6A在哺乳动物早期发育中的作用尚不清楚.
- YTHDC1是一种m6A读取蛋白,在干细胞维护中具有潜在的作用.
研究的目的:
- 研究YTHDC1在小鼠胚胎干细胞中的功能.
- 阐明YTHDC1调节细胞重编程的机制.
- 了解m6ARNA在染色体修饰和逆转移子抑制中的作用.
主要方法:
- 在小鼠ES细胞中删除YTHDC1.
- 对逆转移素活性和表观遗传修饰 (H3K9me3) 的分析.
- 研究YTHDC1,m6ARNAs,SETDB1和Dux之间的相互作用.
主要成果:
- 删除YTHDC1导致细胞重编程到类似2C的状态.
- YTHDC1结合了逆转移体的转录,其耗尽将这些元素重新激活.
- 减少YTHDC1减少了SETDB1介导的H3K9me3,这表明表观遗传失调.
- 在SETDB1的上游,YTHDC1和m6ARNA抑制逆转子和Dux.
结论:
- YTHDC1对于维持小鼠ES细胞以m6A依赖的方式至关重要.
- YTHDC1和m6ARNA在抑制逆转移子和2C类程序方面发挥着关键作用.
- 这项研究揭示了一种涉及m6ARNA,YTHDC1和SETDB1在早期发育过程中的表观遗传控制的新途径.
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