在视网膜发育过程中,METTL3将染色质可访问性从转录分离
Jing Xu1, Yuanhao Huang2, Zhaowei Han2
1Department of Ophthalmology & Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, 1000 Wall St., Ann Arbor, MI 48105, USA.
Stem cell reports
|October 24, 2025
概括
甲基转移酶类3 (METTL3) 酶对视网膜发育至关重要,通过m6A修饰调节RNA稳定性和基因表达. 它的表皮转录学作用影响视网膜原生细胞分化和早期视网膜形形成.
科学领域:
- 发展生物学 发展生物学
- 在RNA生物学,RNA生物学.
- 基因组学就是基因组学.
背景情况:
- METTL3是RNA代谢的关键调节者,但其在组织发育中的作用尚不清楚.
- 视网膜原生细胞 (RPC) 的分化对眼睛发育至关重要,需要精确的基因调节.
研究的目的:
- 通过使用3D视网膜器官来研究METTL3在视网膜发育中的基因组和表谱功能.
- 剖析METTL3影响RPC分化和视网膜anlage形成的分子机制.
主要方法:
- 综合的多omics方法包括m6A分析 (GLORI),ChIP-seq,CUT&RUN,ATAC-seq,和向的表体转录基因工程 (dCas13b-FTO).
- 在RPC中利用了基于degron的METTL3降解和蛋白质-RNA相互作用概况.
- 使用来自胚胎干细胞的3D视网膜器官来模拟视网膜发育.
主要成果:
- 丢失METTL3破坏了视网膜带的形成,证明了它在视网膜早期发育中的关键作用.
- 在Six3 3'UTR的m6A修饰被确定为Six3 mRNA稳定性的关键调节者.
- METTL3影响了染色质可访问性和基因组修饰,但直接的染色质标显示出有限的转录相关性.
- 发现了一个METTL3-Ythdf1蛋白-RNA轴,突出显示了RPCs的快速调节转变.
结论:
- 依赖METTL3的m6A修饰是视网膜发育中的关键表皮转录层.
- 这项研究揭示了一个新的范式,在这种范式中,染色质的可访问性可能与转录输出有所不同.
- 这项工作提供了关于表体转录学,基因组学和发育过程之间的复杂相互作用的见解.
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