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Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions
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Methylation of cytosines in the mammalian genome represents a key epigenetic modification and is dynamically regulated during development. Compelling evidence now suggests that dynamic regulation of DNA methylation is mainly achieved through a cyclic enzymatic cascade comprised of cytosine methylation, iterative oxidation of methyl group by TET dioxygenases, and restoration of unmodified cytosines by either replication-dependent dilution or DNA glycosylase-initiated base excision repair. In this review, we discuss the mechanism and function of DNA demethylation in mammalian genomes, focusing particularly on how developmental modulation of the cytosine-modifying pathway is coupled to active reversal of DNA methylation in diverse biological processes.
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“Although sequencing-based approaches have only found 5hmC in CG dinucleotides in mESC and brain cortical tissue (24), 5hmCH accounted for 38% of 5mCH+5hmCH in cerebellar granule cells, suggesting that 5mCH is also targeted for TET mediated methylation turnover (40).”
From Dynamic DNA methylation: In the right place at the right time (2018) · cites this paper as [24]
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Metadata
- Authors
- Wu, H., & Zhang, Y.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Zhang, Yi
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 156
- Issue
- 1-2
- Pages
- 45-68
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3938284
- OpenAlex
- W2036848594
- Cited by
- 1,065
- References
- 219
- Citations by year
- 2026: 36 · 2025: 57 · 2024: 54 · 2023: 66 · 2022: 83 · 2021: 64 · 2020: 96 · 2019: 106 · 2018: 98 · 2017: 110 · 2016: 114 · 2015: 100 · 2014: 80
- FWCI
- 55.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences (GM68804, R01GM068804)
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK089565)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNA demethylation, DNA methylation, TET enzymes, base excision repair, DNA glycosylase, epigenetic regulation, developmental regulation, mammalian genomes
- MeSH terms
- Animals, Humans, Oxidoreductases, N-Demethylating, Promoter Regions, Genetic, Genome, DNA Methylation, 5-Methylcytosine
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