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Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells.

Molecular cell | May 19, 2011 |

Xu, Yufei | Wu, Feizhen | Tan, Li | Kong, Lingchun | Xiong, Lijun | Deng, Jie | Barbera, Andrew J | Zheng, Lijuan | Zhang, Haikuo | Huang, Stephen | Min, Jinrong | Nicholson, Thomas | Chen, Taiping | Xu, Guoliang | Shi, Yang | Zhang, Kun | Shi, Yujiang Geno
Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.

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- ... rential maintenance of DNA methylation status at Tet1 targets, ultimately contributing to mESC differentiation and the onset of embryonic development.

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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Nihms290592f1
Fig 1. Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.
Nihms290592f1
Fig 1. Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.

Fig 1

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Fig 2. Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.
Nihms290592f2
Fig 2. Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.

Fig 2

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Fig 3. Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.
Nihms290592f3
Fig 3. Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.

Fig 3

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Fig 4. Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.
Nihms290592f4
Fig 4. Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.

Fig 4

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Fig 5. Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.
Nihms290592f5
Fig 5. Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.

Fig 5

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Fig 6. Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.
Nihms290592f6
Fig 6. Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.

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Fig 7. Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.
Nihms290592f7
Fig 7. Xu, Wu, et al. "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells." Molecular cell 42.4 (2011): 451-64. Web.

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