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Genome-wide Regulation of 5hmC, 5mC, and Gene Expression by Tet1 Hydroxylase in Mouse Embryonic Stem Cells
Open accessAbstract
SUMMARY 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 unmodified C, 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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“Wild-type IDH1/2 converts isocitrate to a-KG, whereas mutant IDH enzymes produce 2-hydroxyglutarate (2-HG), an oncometabolite that competitively inhibit many a-KG-dependent dioxygenases, including TET proteins (Figueroa et al., 2010; Xu et al., 2011a).”
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Metadata
- Authors
- 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.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 42
- Issue
- 4
- Pages
- 451-464
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2020016210
- Cited by
- 632
- References
- 33
- FWCI
- 27.74
- Type
- journal article
- Language
- en
- Open access
- bronze
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