Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
Open accessAbstract
Methylation Mediation: Methylation of cytosine bases, 5-methylcytosine (5mC), in DNA plays an important regulatory role in mammalian genomes. Methylation patterns are often inherited across generations, but they can also be dynamic, suggesting that active DNA demethylation pathways exist. One such pathway, best characterized in plants, involves the removal of the 5mC base, and its replacement by C, via a DNA repair mechanism. Kriaucionis and Heintz (p. 929 , published online 16 April) now show that, as well as 5mC in mammalian genomes, there are also significant amounts of 5-hydroxymethylcytosine (5hmC) in DNA of Purkinje neurons, which have large nuclei with apparently very little heterochromatin. Tahiliani et al. (p. 930, published online 16 April) find that the protein TET1 is capable of converting 5mC into 5hmC both in vitro and in vivo. 5-Hydroxymethylcytosine is also present in embryonic stem cells, and levels of 5hmC and TET1 show correlated variation during cell differentiation.
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5hmC abundance represents only ~10% of the 5mC level in embryonic stem cells.
“Furthermore, it has previously been shown that 5hmC abundance represents only ~10% of the 5mC level in embryonic stem cells,(45), thus changes in 5mC upon HNF4A depletion in the whole liver may be difficult to observe.”
From Hepatocyte Nuclear Factor 4‐Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver (2019) · cites this paper as [45]
The passage describing Fig. 5A reports that 5hmC and 5mC account for 4–6% and 55–60%, respectively, of cytosines at MspI cleavage sites in mouse embryonic stem cells—a ratio of roughly 10%. The measurement is limited to those sites, so it does not establish that ratio for all DNA in embryonic stem cells. (LLM, conf=0.84)
Experimental — accuracy not yet measuredTET proteins oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine.
“TET proteins can oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formyl cytosine (5fC), and 5-carboxylcytosine (5caC) (He et al., 2011; Ito et al., 2011; Tahiliani et al., 2009).”
From Influence of Metabolism on Epigenetics and Disease (2013) · cites this paper as Tahiliani et al., 2009
TET proteins convert 5mC to 5hmC, 5fC, and 5cac.
“TET proteins are responsible for conversion of 5mC in 5hmC [34], 5fC, and 5cac [36].”
From PU.1 target genes undergo Tet2-coupled demethylation and DNMT3b-mediated methylation in monocyte-to-osteoclast differentiation (2013) · cites this paper as [34]
TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine.
“which convert 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC).16”
From RNF217 regulates iron homeostasis through its E3 ubiquitin ligase activity by modulating ferroportin degradation (2021) · cites this paper as [16]
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- Authors
- Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., & Rao, A.
- Affiliations
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Boston Children's Hospital (US)
- National Institutes of Health (US)
- Corresponding author
- Liu, David R.
- Aravind, L.
- Rao, Anjana
- ORCID
- Venue
- Science
- Published
- 2009-05-15
- Volume
- 324
- Issue
- 5929
- Pages
- 930-935
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2715015
- OpenAlex
- W2108664872
- Cited by
- 5,836
- References
- 30
- Citations by year
- 2026: 168 · 2025: 221 · 2024: 265 · 2023: 328 · 2022: 331 · 2021: 354 · 2020: 336 · 2019: 385 · 2018: 412 · 2017: 427 · 2016: 458 · 2015: 418 · 2014: 464 · 2013: 432 · 2012: 333
- FWCI
- 112.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Heart, Lung, and Blood Institute (K08HL089150)
- National Institute of General Medical Sciences (R01GM065865)
- National Institute of Allergy and Infectious Diseases (AI44432, R01AI044432)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- 5-hydroxymethylcytosine, 5-methylcytosine, TET1, DNA demethylation, cytosine methylation, Purkinje cells, embryonic stem cells, cell differentiation, heterochromatin
- MeSH terms
- Amino Acid Sequence, Animals, Cell Line, Cytosine, DNA, DNA-Binding Proteins, Humans, Mixed Function Oxygenases, Hydroxylation, Molecular Sequence Data, Proto-Oncogene Proteins, Mass Spectrometry, Transfection, Dinucleoside Phosphates, Sequence Alignment, DNA Methylation, RNA Interference, 5-Methylcytosine, Mice, Embryonic Stem Cells
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