Dnmt3bas坐标转录诱导和替代的外显子包含,以促进催化活性Dnmt3b表达
Mohd Saleem Dar1, Isaiah K Mensah1, Ming He1
1Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
Cell reports
|June 9, 2023
概括
一种新的长非编码RNA,Dnmt3bas,通过控制DNMT3B基因表达和胚胎发育期间的替代拼接来调节DNA甲基化. 这确保了精确的DNA甲基化模式.
科学领域:
- 表观遗传学和基因调控
- 分子生物学分子生物学
- 发育生物学 发展生物学
背景情况:
- 胚胎DNA甲基转移酶3β (DNMT3B) 的表达对于建立新的DNA甲基化模式至关重要.
- 精确调节DNMT3B表达及其异型对正常胚胎发育至关重要.
研究的目的:
- 阐明胚胎干细胞 (ESC) 分化过程中DNMT3B表达和替代拼接的调节机制.
- 研究长非编码RNA Dnmt3bas在控制DNMT3B调控中的作用.
主要方法:
- 研究了Dnmt3bas与聚合体抑制复合体2 (PRC2) 和异质核核核糖核蛋白蛋白L (hnRNPL) 的相互作用.
- 利用ESC中Dnmt3bas的淘汰和过度表达来评估其对Dnmt3b转录和拼接的影响.
- 分析了Dnmt3bas对活性 (DNMT3B1) 与非活性 (DNMT3B6) DNMT3B异型体的比率的影响.
主要成果:
- Dnmt3bas将PRC2招募到Dnmt3b的cis-regulatory元素中,调节其基本表达.
- Dnmt3bas的淘汰增强了DNMT3B的转录诱导,而其过度表达则抑制了它.
- Dnmt3bas促进了异构体的包含,通过与hnrnpl的相互作用,有利于活性DNMT3B1异构体而非非活性DNMT3B6异构体.
- Dnmt3bas促进了hnRNPL和RNA聚合酶II (RNA Pol II) 在Dnmt3b促进体之间的相互作用.
结论:
- 在ESC分化过程中,Dnmt3bas作为DNMT3B表达和替代拼接的关键调节者.
- 这种双重调节机制确保了对催化活性DNMT3B的精确控制,并保持了新型DNA甲基化的忠实性.
- Dnmt3bas在协调转录诱导和Dnmt3b的替代拼接方面发挥着关键作用,影响发育中的表观遗传调节.
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