FTO 介导 LINE1 mA 去甲基化和染色质调控在 mESCs 和小鼠发育中的作用。
FTO mediates LINE1 mA demethylation and chromatin regulation in mESCs and mouse development.
机构信息
Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
Howard Hughes Medical Institute, The University of Chicago, Chicago, Chicago, IL 60637, USA.
出版信息
Science. 2022 May 27;376(6596):968-973. doi: 10.1126/science.abe9582. Epub 2022 May 5.
-methyladenosine (mA) is the most abundant internal modification on mammalian messenger RNA. It is installed by a writer complex and can be reversed by erasers such as the fat mass and obesity-associated protein FTO. Despite extensive research, the primary physiological substrates of FTO in mammalian tissues and development remain elusive. Here, we show that FTO mediates mA demethylation of long-interspersed element-1 (LINE1) RNA in mouse embryonic stem cells (mESCs), regulating LINE1 RNA abundance and the local chromatin state, which in turn modulates the transcription of LINE1-containing genes. FTO-mediated LINE1 RNA mA demethylation also plays regulatory roles in shaping chromatin state and gene expression during mouse oocyte and embryonic development. Our results suggest broad effects of LINE1 RNA mA demethylation by FTO in mammals.
N6-甲基腺嘌呤（m6A）是哺乳动物信使 RNA 上最丰富的内部修饰。它由一个作家复合物安装，可以被橡皮擦如肥胖相关蛋白 FTO 逆转。尽管进行了广泛的研究，但 FTO 在哺乳动物组织和发育中的主要生理底物仍然难以捉摸。在这里，我们表明 FTO 介导小鼠胚胎干细胞（mESCs）中长散布元件-1（LINE1）RNA 的 m6A 去甲基化，调节 LINE1 RNA 的丰度和局部染色质状态，进而调节包含 LINE1 的基因的转录。FTO 介导的 LINE1 RNA m6A 去甲基化在小鼠卵母细胞和胚胎发育过程中也对塑造染色质状态和基因表达起调节作用。我们的结果表明，FTO 在哺乳动物中对 LINE1 RNA m6A 去甲基化有广泛的影响。
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