在 lysine 36 导向的 histone H3 三甲基化 m6A RNA 修改共转录
Huilin Huang1,2, Hengyou Weng1,2, Keren Zhou3,4
1Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA, USA.
Nature
|March 15, 2019
概括
在Lys36 (H3K36me3) 中的Histon H3三甲基化引导N6-甲基氨酸 (m6A) 的mRNA修饰沉积. 基因组标记和RNA甲基化之间的交叉声会显示出一种新的基因表达调节层.
科学领域:
- 分子生物学
- 表观遗传学
- 核糖核酸生物学
背景情况:
- 基因和基因素的修改显著影响基因表达.
- N6-甲基氨酸 (m6A) 是一种常见的mRNA修饰,可以在转录后调节基因表达.
- 控制m6A在转录组中的沉积的精确机制在很大程度上是未知的.
研究的目的:
- 阐明 histone 修饰如何影响 m6A 在 mRNA 上的特定和动态沉积.
- 在Lys36 (H3K36me3) 导向m6A甲基化的作用.
- 发现H3K36me3与m6A甲基转移酶复合体之间的分子相互作用.
主要方法:
- 通过ChIP-seq识别H3K36me3峰值并评估m6A丰富度.
- 耗尽H3K36me3以评估其对m6A水平的全球影响.
- 生物化学试验以确定METTL14与H3K36me3的直接结合.
- 在小鼠胚胎干细胞中对METTL14和H3K36me3干扰反应的m6A丰度的分析.
主要成果:
- 在H3K36me3峰值附近的m6A修饰显著丰富,在H3K36me3耗尽时总体减少.
- H3K36me3直接与METTL14结合,这是m6A甲基转移酶复合物的关键组成部分.
- 这种相互作用通过将m6A机制招募到积极转录的区域,从而促进共转录m6A沉积到新生的RNA.
- 在小鼠胚胎干细胞中减少H3K36me3或METTL14会降低m6A水平并增强干性.
结论:
- 基因组H3K36me3是m6A在mRNA中的特定和动态沉积的关键决定因素.
- METTL14直接识别H3K36me3,将基因组修饰与RNA甲基化联系起来.
- 这项研究揭示了基因表达调节的新层通过基因组修饰和RNA甲基化之间的交叉声.
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