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

Wei, Jiangbo, Yu, Xianbin, Yang, Lei, Liu, Xuelian, Gao, Boyang, Huang, Boxian, Dou, Xiaoyang, Liu, Jun, Zou, Zhongyu, Cui, Xiao-Long, Zhang, Li-Sheng, Zhao, Xingsen, Liu, Qinzhe, He, P. Cody, Sepich-Poore, Caraline, Zhong, Nicole, Liu, Wenqiang, Li, Yanhe, Kou, Xiaochen, Zhao, Yanhong, Wu, You, Cheng, Xuejun, Chen, Chuan, An, Yiming, Dong, Xueyang, Wang, Huanyu, Shu, Qiang, Hao, Ziyang, Duan, Tao, He, Yu-Ying, Li, Xuekun, Gao, Shaorong, Gao, Yawei, He, Chuan·2022·Science
DOI 10.1126/science.abe9582PMC PMC9746489
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Abstract

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.

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Metadata

Authors
Wei, J., Yu, X., Yang, L., Liu, X., Gao, B., Huang, B., Dou, X., Liu, J., Zou, Z., Cui, X.-L., Zhang, L.-S., Zhao, X., Liu, Q., He, P. C., Sepich-Poore, C., Zhong, N., Liu, W., Li, Y., Kou, X., Zhao, Y., Wu, Y., Cheng, X., Chen, C., An, Y., Dong, X., Wang, H., Shu, Q., Hao, Z., Duan, T., He, Y.-Y., Li, X., Gao, S., Gao, Y., & He, C.
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2022-05-27
Volume
376
Issue
6596
Pages
968-973
ISSN
  • 0036-8075
  • 1095-9203
DOI
10.1126/science.abe9582
PMC
PMC9746489
Cited by
294
References
14
Language
en

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CoChat. (2026). Citation check: FTO mediates LINE1 m 6 A demethylation and chromatin regulation in mESCs and mouse development. https://app.cochat.ai/papers/10.1126/science.abe9582
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Wei, J., Yu, X., Yang, L., Liu, X., Gao, B., Huang, B., Dou, X., Liu, J., Zou, Z., Cui, X.-L., Zhang, L.-S., Zhao, X., Liu, Q., He, P. C., Sepich-Poore, C., Zhong, N., Liu, W., Li, Y., Kou, X., . . . He, C. (2022). FTO mediates LINE1 m 6 A demethylation and chromatin regulation in mESCs and mouse development. Science. https://doi.org/10.1126/science.abe9582