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在mESC和小鼠发育中调节甲基解和染色质

Jiangbo Wei^1,2, Xianbin Yu^1,2, Lei Yang^3,4

¹Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.

Science (New York, N.Y.)

|May 5, 2022

概括

脂肪质量和与肥胖相关的蛋白质 (FTO) 从LINE1RNA中删除了N6-甲基氨酸 (m6A) 修饰. 在小鼠发育过程中,这种脱甲基化调节LINE1RNA水平和基因表达.

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:

N6-甲基氨酸 (m6A) 是哺乳动物信使RNA中最常见的内部修饰.
脂肪质量和与肥胖相关的蛋白质 (FTO) 是一个关键的m6A"清除剂",其生理基质在很大程度上是未知的.
了解FTO的目标对于解读它在哺乳动物发育和疾病中的作用至关重要.

研究的目的:

在哺乳动物细胞和发育中确定FTO的主要生理基质.
研究FTO介导的m6A脱甲基化对特定RNA分子和细胞过程的功能后果.

主要方法:

使用小鼠胚胎干细胞 (mESC) 和小鼠卵细胞进行实验分析.
研究了FTO和长间隔元素-1 (LINE1) RNA之间的相互作用.
评估了m6A脱甲基化,RNA丰度,染色质状态和基因表达.

主要成果:

证明FTO在mESC中调解了LINE1RNA的m6A脱甲基化.
显示FTO调节LINE1RNA丰度和局部染色质状态.
发现FTO介导的LINE1RNA脱甲基化会影响LINE1含有的基因的转录.
在小鼠卵细胞和胚胎发育过程中揭示了染色质状态和基因表达的调节作用.

结论:

在哺乳动物中,FTO在LINE1RNA的m6A脱甲基化中起着重要作用.
这种表观遗传调节会影响LINE1RNA的丰度,染色体结构和基因表达.
通过FTO介导的LINE1RNA脱甲基化对哺乳动物发育和潜在的其他生物过程具有广泛的影响.

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