FTO mediates LINE1 m6A demethylation and chromatin regulation in mESCs and mouse development

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

doi:10.1126/science.abe9582

FTO mediates LINE1 m⁶A demethylation and chromatin regulation in mESCs and mouse development

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 ZhaoYou 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

209 Citations (Scopus)

Abstract

N⁶-methyladenosine (m⁶A) 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 m⁶A 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 m⁶A 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 m⁶A demethylation by FTO in mammals.

Original language	English
Article number	eabe9582
Journal	Science
Volume	376
Issue number	6596
DOIs	https://doi.org/10.1126/science.abe9582
Publication status	Published - 27 May 2022
Externally published	Yes

Bibliographical note

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© 2022 American Association for the Advancement of Science. All rights reserved.

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1126/science.abe9582

Cite this

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 m⁶A demethylation and chromatin regulation in mESCs and mouse development. Science, 376(6596), Article eabe9582. https://doi.org/10.1126/science.abe9582

@article{8246dc8b906c437ca80a5d3da86a3c98,

title = "FTO mediates LINE1 m6A demethylation and chromatin regulation in mESCs and mouse development",

abstract = "N6-methyladenosine (m6A) 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 m6A 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 m6A 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 m6A demethylation by FTO in mammals.",

author = "Jiangbo Wei and Xianbin Yu and Lei Yang and Xuelian Liu and Boyang Gao and Boxian Huang and Xiaoyang Dou and Jun Liu and Zhongyu Zou and Cui, \{Xiao Long\} and Zhang, \{Li Sheng\} and Xingsen Zhao and Qinzhe Liu and He, \{P. Cody\} and Caraline Sepich-Poore and Nicole Zhong and Wenqiang Liu and Yanhe Li and Xiaochen Kou and Yanhong Zhao and You Wu and Xuejun Cheng and Chuan Chen and Yiming An and Xueyang Dong and Huanyu Wang and Qiang Shu and Ziyang Hao and Tao Duan and He, \{Yu Ying\} and Xuekun Li and Shaorong Gao and Yawei Gao and Chuan He",

year = "2022",

month = may,

day = "27",

doi = "10.1126/science.abe9582",

language = "English",

volume = "376",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6596",

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Wei, J, Yu, X, Yang, L, Liu, X, Gao, B, Huang, B, Dou, X, Liu, J, Zou, Z, Cui, XL, Zhang, LS, Zhao, X, Liu, Q, He, PC, 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, YY, Li, X, Gao, S, Gao, Y & He, C 2022, 'FTO mediates LINE1 m⁶A demethylation and chromatin regulation in mESCs and mouse development', Science, vol. 376, no. 6596, eabe9582. https://doi.org/10.1126/science.abe9582

TY - JOUR

T1 - FTO mediates LINE1 m6A demethylation and chromatin regulation in mESCs and mouse development

AU - Wei, Jiangbo

AU - Yu, Xianbin

AU - Yang, Lei

AU - Liu, Xuelian

AU - Gao, Boyang

AU - Huang, Boxian

AU - Dou, Xiaoyang

AU - Liu, Jun

AU - Zou, Zhongyu

AU - Cui, Xiao Long

AU - Zhang, Li Sheng

AU - Zhao, Xingsen

AU - Liu, Qinzhe

AU - He, P. Cody

AU - Sepich-Poore, Caraline

AU - Zhong, Nicole

AU - Liu, Wenqiang

AU - Li, Yanhe

AU - Kou, Xiaochen

AU - Zhao, Yanhong

AU - Wu, You

AU - Cheng, Xuejun

AU - Chen, Chuan

AU - An, Yiming

AU - Dong, Xueyang

AU - Wang, Huanyu

AU - Shu, Qiang

AU - Hao, Ziyang

AU - Duan, Tao

AU - He, Yu Ying

AU - Li, Xuekun

AU - Gao, Shaorong

AU - Gao, Yawei

AU - He, Chuan

PY - 2022/5/27

Y1 - 2022/5/27

N2 - N6-methyladenosine (m6A) 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 m6A 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 m6A 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 m6A demethylation by FTO in mammals.

AB - N6-methyladenosine (m6A) 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 m6A 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 m6A 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 m6A demethylation by FTO in mammals.

UR - https://www.webofscience.com/wos/woscc/full-record/WOS:000805850000030

UR - https://openalex.org/W4229025118

UR - https://www.scopus.com/pages/publications/85130941590

U2 - 10.1126/science.abe9582

DO - 10.1126/science.abe9582

M3 - Journal Article

C2 - 35511947

SN - 0036-8075

VL - 376

JO - Science

JF - Science

IS - 6596

M1 - eabe9582

ER -