FTO mediates LINE1 m 6 A demethylation and chromatin regulation in mESCs and mouse development

Autor: Jiangbo Wei, Xianbin Yu, Lei Yang, Xuelian Liu, Boyang Gao, Boxian Huang, Xiaoyang Dou, Jun Liu, Zhongyu Zou, Xiao-Long Cui, Li-Sheng Zhang, Xingsen Zhao, Qinzhe Liu, P. Cody He, Caraline Sepich-Poore, Nicole Zhong, Wenqiang Liu, Yanhe Li, Xiaochen Kou, Yanhong Zhao, You Wu, Xuejun Cheng, Chuan Chen, Yiming An, Xueyang Dong, Huanyu Wang, Qiang Shu, Ziyang Hao, Tao Duan, Yu-Ying He, Xuekun Li, Shaorong Gao, Yawei Gao, Chuan He
Rok vydání: 2022
Předmět:
Zdroj: Science
ISSN: 1095-9203
0036-8075
DOI: 10.1126/science.abe9582
Popis: N 6 -methyladenosine (m 6 A) 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 m 6 A 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 m 6 A 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 m 6 A demethylation by FTO in mammals.
Databáze: OpenAIRE
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