Genome-wide Regulation of 5hmC, 5mC, and Gene Expression by Tet1 Hydroxylase in Mouse Embryonic Stem Cells

Yufei Xu; Feizhen Wu; Li Tan; Lingchun Kong; Lijun Xiong; Jie Deng; Andrew J. Barbera; Lijuan Zheng; Haikuo Zhang; Stephen Huang; Jinrong Min; Thomas Nicholson; Taiping Chen; Guoliang Xu; Yang Shi; Kun Zhang; Yujiang Geno Shi

doi:10.1016/j.molcel.2011.04.005

Genome-wide Regulation of 5hmC, 5mC, and Gene Expression by Tet1 Hydroxylase in Mouse Embryonic Stem Cells

Yufei Xu, Feizhen Wu, Li Tan, Lingchun Kong, Lijun Xiong, Jie Deng, Andrew J. Barbera, Lijuan Zheng, Haikuo Zhang, Stephen Huang, Jinrong Min, Thomas Nicholson, Taiping Chen, Guoliang Xu, Yang Shi, Kun Zhang, Yujiang Geno Shi

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

531 Scopus citations

Abstract

DNA methylation at the 5 position of cytosine (5mC) in the mammalian genome is a key epigenetic event critical for various cellular processes. The ten-eleven translocation (Tet) family of 5mC-hydroxylases, which convert 5mC to 5-hydroxymethylcytosine (5hmC), offers a way for dynamic regulation of DNA methylation. Here we report that Tet1 binds to unmodified C or 5mC- or 5hmC-modified CpG-rich DNA through its CXXC domain. Genome-wide mapping of Tet1 and 5hmC reveals mechanisms by which Tet1 controls 5hmC and 5mC levels in mouse embryonic stem cells (mESCs). We also uncover a comprehensive gene network influenced by Tet1. Collectively, our data suggest that Tet1 controls DNA methylation both by binding to CpG-rich regions to prevent unwanted DNA methyltransferase activity, and by converting 5mC to 5hmC through hydroxylase activity. This Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 targets, ultimately contributing to mESC differentiation and the onset of embryonic development.

Original language	English
Pages (from-to)	451-464
Number of pages	14
Journal	Molecular Cell
Volume	42
Issue number	4
DOIs	https://doi.org/10.1016/j.molcel.2011.04.005
State	Published - 20 May 2011
Externally published	Yes

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Xu, Y., Wu, F., Tan, L., Kong, L., Xiong, L., Deng, J., Barbera, A. J., Zheng, L., Zhang, H., Huang, S., Min, J., Nicholson, T., Chen, T., Xu, G., Shi, Y., Zhang, K., & Shi, Y. G. (2011). Genome-wide Regulation of 5hmC, 5mC, and Gene Expression by Tet1 Hydroxylase in Mouse Embryonic Stem Cells. Molecular Cell, 42(4), 451-464. https://doi.org/10.1016/j.molcel.2011.04.005

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title = "Genome-wide Regulation of 5hmC, 5mC, and Gene Expression by Tet1 Hydroxylase in Mouse Embryonic Stem Cells",

abstract = "DNA methylation at the 5 position of cytosine (5mC) in the mammalian genome is a key epigenetic event critical for various cellular processes. The ten-eleven translocation (Tet) family of 5mC-hydroxylases, which convert 5mC to 5-hydroxymethylcytosine (5hmC), offers a way for dynamic regulation of DNA methylation. Here we report that Tet1 binds to unmodified C or 5mC- or 5hmC-modified CpG-rich DNA through its CXXC domain. Genome-wide mapping of Tet1 and 5hmC reveals mechanisms by which Tet1 controls 5hmC and 5mC levels in mouse embryonic stem cells (mESCs). We also uncover a comprehensive gene network influenced by Tet1. Collectively, our data suggest that Tet1 controls DNA methylation both by binding to CpG-rich regions to prevent unwanted DNA methyltransferase activity, and by converting 5mC to 5hmC through hydroxylase activity. This Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 targets, ultimately contributing to mESC differentiation and the onset of embryonic development.",

author = "Yufei Xu and Feizhen Wu and Li Tan and Lingchun Kong and Lijun Xiong and Jie Deng and Barbera, {Andrew J.} and Lijuan Zheng and Haikuo Zhang and Stephen Huang and Jinrong Min and Thomas Nicholson and Taiping Chen and Guoliang Xu and Yang Shi and Kun Zhang and Shi, {Yujiang Geno}",

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T1 - Genome-wide Regulation of 5hmC, 5mC, and Gene Expression by Tet1 Hydroxylase in Mouse Embryonic Stem Cells

AU - Xu, Yufei

AU - Wu, Feizhen

AU - Tan, Li

AU - Kong, Lingchun

AU - Xiong, Lijun

AU - Deng, Jie

AU - Barbera, Andrew J.

AU - Zheng, Lijuan

AU - Zhang, Haikuo

AU - Huang, Stephen

AU - Min, Jinrong

AU - Nicholson, Thomas

AU - Chen, Taiping

AU - Xu, Guoliang

AU - Shi, Yang

AU - Zhang, Kun

AU - Shi, Yujiang Geno

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N2 - DNA methylation at the 5 position of cytosine (5mC) in the mammalian genome is a key epigenetic event critical for various cellular processes. The ten-eleven translocation (Tet) family of 5mC-hydroxylases, which convert 5mC to 5-hydroxymethylcytosine (5hmC), offers a way for dynamic regulation of DNA methylation. Here we report that Tet1 binds to unmodified C or 5mC- or 5hmC-modified CpG-rich DNA through its CXXC domain. Genome-wide mapping of Tet1 and 5hmC reveals mechanisms by which Tet1 controls 5hmC and 5mC levels in mouse embryonic stem cells (mESCs). We also uncover a comprehensive gene network influenced by Tet1. Collectively, our data suggest that Tet1 controls DNA methylation both by binding to CpG-rich regions to prevent unwanted DNA methyltransferase activity, and by converting 5mC to 5hmC through hydroxylase activity. This Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 targets, ultimately contributing to mESC differentiation and the onset of embryonic development.

AB - DNA methylation at the 5 position of cytosine (5mC) in the mammalian genome is a key epigenetic event critical for various cellular processes. The ten-eleven translocation (Tet) family of 5mC-hydroxylases, which convert 5mC to 5-hydroxymethylcytosine (5hmC), offers a way for dynamic regulation of DNA methylation. Here we report that Tet1 binds to unmodified C or 5mC- or 5hmC-modified CpG-rich DNA through its CXXC domain. Genome-wide mapping of Tet1 and 5hmC reveals mechanisms by which Tet1 controls 5hmC and 5mC levels in mouse embryonic stem cells (mESCs). We also uncover a comprehensive gene network influenced by Tet1. Collectively, our data suggest that Tet1 controls DNA methylation both by binding to CpG-rich regions to prevent unwanted DNA methyltransferase activity, and by converting 5mC to 5hmC through hydroxylase activity. This Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 targets, ultimately contributing to mESC differentiation and the onset of embryonic development.

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Genome-wide Regulation of 5hmC, 5mC, and Gene Expression by Tet1 Hydroxylase in Mouse Embryonic Stem Cells

Abstract

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