User:CER20G/Hydroxymethylation
Hydroxymethylation in demethylation[edit]
[edit]5-Methylcytosine is a common epigenetic marker. The methyl group is modified by oxidation of the methyl group in a process called hydroxymethylation:
- RCH3 + O → RCH2OH
This oxidation is thought to be a prelude to removal, regenerating cytosine.
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Hydroxymethylation in DNA Demethylation
[edit]5-methylcytosine (5mC), a common and highly stable epigenetic marker which mediates long-term gene silencing, can be converted to 5-hydroxymethylcytosine (5hmC) via enzymatic oxidation[1].
- RCH3 + O → RCH2OH
In mammals this enzymatic oxidation occurs via a family of enzymes known as TET (ten eleven translocation) methylcytosine dioxygenases; of which, there are three variants: TET1, TET2, & TET3[2]. TET enzymes can further oxidize 5hmC to form formylcytosine (5fC) and carboxylcytosine (5caC)[3]. Recognition of 5caC and 5fC by thymine-DNA glycosylase (TDG) coupled with the base-excision repair (BER) pathway results in excision of the oxidized variant which is replaced by an unmethylated cytosine[1].
References
[edit]- ^ a b Bochtler, Matthias; Kolano, Agnieszka; Xu, Guo-Liang (2017-01). "DNA demethylation pathways: Additional players and regulators". BioEssays. 39 (1): e201600178. doi:10.1002/bies.201600178.
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(help) - ^ a b Bayraktar, Gonca; Kreutz, Michael R. (2018-05-23). "The Role of Activity-Dependent DNA Demethylation in the Adult Brain and in Neurological Disorders". Frontiers in Molecular Neuroscience. 11: 169. doi:10.3389/fnmol.2018.00169. ISSN 1662-5099. PMC 5975432. PMID 29875631.
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: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ Tahiliani, Mamta; Koh, Kian Peng; Shen, Yinghua; Pastor, William A.; Bandukwala, Hozefa; Brudno, Yevgeny; Agarwal, Suneet; Iyer, Lakshminarayan M.; Liu, David R.; Aravind, L.; Rao, Anjana (2009-05-15). "Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1". Science. 324 (5929): 930–935. doi:10.1126/science.1170116. PMC 2715015. PMID 19372391.
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: CS1 maint: PMC format (link)