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A Method to Study de novo Formation of Chromatin Domains
Published on: August 23, 2019
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METTL14调节小鼠胚胎干细胞中的染色质双价位域
Mandi Mu1, Xinze Li1, Li Dong1
1Longevity and Aging Institute, the Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Cell reports
|June 14, 2023
概括
甲基转移酶样14 (METTL14) 调节小鼠胚胎干细胞中的双价域,独立于METTL3. 它通过影响基因素甲基化标记来维持染色质的完整性,从而影响基因转录.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因组RNA的修饰 基因组RNA的修饰
- 干细胞生物学 干细胞生物学
背景情况:
- METTL14是一种RNA结合蛋白,参与N6-甲基氨酸 (m6A) 甲基化,与METTL3.3合作.
- 已知METTL3在小鼠胚胎干细胞 (mESC) 中的异染色素中的作用,但METTL14在mESC中的染色素功能尚不清楚.
研究的目的:
- 调查METTL14在mESCs中的染色质上的分子功能.
- 阐明METTL14在调节双价位域和相关的质子修饰中的作用.
主要方法:
- 染色体免疫沉 (ChIP) 试验用于分析组 histone 的修饰 (H3K27me3,H3K4me3).
- 在mESC中进行基因淘汰研究 (Mettl14淘汰).
- 对基因转录水平的分析.
- 蛋白质-蛋白质相互作用研究以确定 PRC2 和 KDM5B.等相互作用伙伴.
主要成果:
- METTL14特别结合和调节由H3K27me3和H3K4me3.3标记的双价位域.
- 甲基14淘汰导致H3K27me3降低和H3K4me3增加,导致转录升高.
- METTL14对双价域的调节独立于METTL3和m6A修改.
- METTL14与PRC2和KDM5B相互作用,可能会将它们招募到染色质中,以调节H3K27me3和H3K4me3水平.
结论:
- 在维护mESCs中的双价域完整性方面,METTL14发挥着关键的,METTL3独立的作用.
- METTL14通过与PRC2和KDM5B的相互作用来调节激素甲基化,有助于表观遗传调节.
- 这项研究揭示了哺乳动物双价域调节的新机制,突出了METTL14的直接染色质功能.
关键词:
科普:分子生物学 分子生物学相关概念视频
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