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TET enzymes, TDG and the dynamics of DNA demethylation

Author

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  • Rahul M. Kohli

    (Raymond and Ruth Perelman School of Medicine, University of Pennsylvania
    Raymond and Ruth Perelman School of Medicine, University of Pennsylvania)

  • Yi Zhang

    (Howard Hughes Medical Institute, WAB-1496, 200 Longwood Ave.
    Program in Cellular and Molecular Medicine, Boston Children's Hospital
    Boston Children's Hospital
    Harvard Medical School)

Abstract

DNA methylation has a profound impact on genome stability, transcription and development. Although enzymes that catalyse DNA methylation have been well characterized, those that are involved in methyl group removal have remained elusive, until recently. The transformative discovery that ten-eleven translocation (TET) family enzymes can oxidize 5-methylcytosine has greatly advanced our understanding of DNA demethylation. 5-Hydroxymethylcytosine is a key nexus in demethylation that can either be passively depleted through DNA replication or actively reverted to cytosine through iterative oxidation and thymine DNA glycosylase (TDG)-mediated base excision repair. Methylation, oxidation and repair now offer a model for a complete cycle of dynamic cytosine modification, with mounting evidence for its significance in the biological processes known to involve active demethylation.

Suggested Citation

  • Rahul M. Kohli & Yi Zhang, 2013. "TET enzymes, TDG and the dynamics of DNA demethylation," Nature, Nature, vol. 502(7472), pages 472-479, October.
    • Handle: RePEc:nat:nature:v:502:y:2013:i:7472:d:10.1038_nature12750
    DOI: 10.1038/nature12750
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    Cited by:

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    2. Amadou Gaye & Gary H Gibbons & Charles Barry & Rakale Quarells & Sharon K Davis, 2017. "Influence of socioeconomic status on the whole blood transcriptome in African Americans," PLOS ONE, Public Library of Science, vol. 12(12), pages 1-15, December.
    3. Liu Yang & San-Jian Yu & Qi Hong & Yu Yang & Zhi-Ming Shao, 2015. "Reduced Expression of TET1, TET2, TET3 and TDG mRNAs Are Associated with Poor Prognosis of Patients with Early Breast Cancer," PLOS ONE, Public Library of Science, vol. 10(7), pages 1-10, July.
    4. Qing Li & Jiansen Lu & Xidi Yin & Yunjian Chang & Chao Wang & Meng Yan & Li Feng & Yanbo Cheng & Yun Gao & Beiying Xu & Yao Zhang & Yingyi Wang & Guizhong Cui & Luang Xu & Yidi Sun & Rong Zeng & Yixue, 2023. "Base editing-mediated one-step inactivation of the Dnmt gene family reveals critical roles of DNA methylation during mouse gastrulation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    5. Jiří Kudrna & Marek Popov & František Hnilička & Marie Lhotská & Veronika Zemanová & Pavla Vachová & Jan Kubeš & Jana Česká & Barbora Tunklová, 2023. "Effects of Acetaminophen Contamination on 5-Methylcytosine Content in Zea mays and Plant Physiological Parameters," Agriculture, MDPI, vol. 13(7), pages 1-12, June.
    6. Simon D. Schwarz & Jianming Xu & Kapila Gunasekera & David Schürmann & Cathrine B. Vågbø & Elena Ferrari & Geir Slupphaug & Michael O. Hottiger & Primo Schär & Roland Steinacher, 2024. "Covalent PARylation of DNA base excision repair proteins regulates DNA demethylation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Allegra Angeloni & Skye Fissette & Deniz Kaya & Jillian M. Hammond & Hasindu Gamaarachchi & Ira W. Deveson & Robert J. Klose & Weiming Li & Xiaotian Zhang & Ozren Bogdanovic, 2024. "Extensive DNA methylome rearrangement during early lamprey embryogenesis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    8. Yidong Song & Qianmu Yuan & Sheng Chen & Yuansong Zeng & Huiying Zhao & Yuedong Yang, 2024. "Accurately predicting enzyme functions through geometric graph learning on ESMFold-predicted structures," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    9. John W. Oller & Christopher A. Shaw, 2019. "From Superficial Damage to Invasion of the Nucleosome: Ranking of Morbidities by the Biosemiotic Depth Hypothesis," International Journal of Sciences, Office ijSciences, vol. 8(06), pages 51-73, June.
    10. Letizia Pitto & Francesca Gorini & Fabrizio Bianchi & Elena Guzzolino, 2020. "New Insights into Mechanisms of Endocrine-Disrupting Chemicals in Thyroid Diseases: The Epigenetic Way," IJERPH, MDPI, vol. 17(21), pages 1-18, October.

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