Abstract
Mammalian DNA methylation mainly occurs at the carbon-C5 position of cytosine (5mC). TET enzymes were discovered to successively oxidize 5mC to 5-hydromethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). TET enzymes and oxidized 5mC derivatives play important roles in various biological and pathological processes, including regulation of DNA demethylation, gene transcription, embryonic development, and oncogenesis. In this chapter, we will discuss the discovery of TET-mediated 5mC oxidation and the structure, function, and regulation of TET enzymes.
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Abbreviations
- 2HG:
-
2-Hydroxyglutarate
- 5caC:
-
5-Carboxylcytosine
- 5fC:
-
5-Formylcytosine
- 5hmC:
-
5-Hydromethylcytosine
- 5hmrC:
-
5-Hydroxymethylcytidine
- 5mC:
-
5-Methylcytosine
- 5mrC:
-
5-Methylcytidine
- 6mA:
-
N6-methyladenine
- ABH2:
-
AlkB homolog 2
- AID:
-
Activation-induced deaminase
- AML:
-
Acute myeloid leukemia
- APOBEC:
-
Apolipoprotein B mRNA-editing enzyme complex
- BER:
-
Base excision repair
- CD:
-
Catalytic domain
- Chip-seq:
-
Chromatin immunoprecipitation-sequencing
- CMML:
-
Chronic myelomonocytic leukemia
- CpG:
-
Cytosine-phosphate-guanine
- CXXC:
-
Cysteine-X-X-cysteine
- Cys-C:
-
Cys-rich C-terminal
- Cys-N:
-
Cys-rich N-terminal
- Cys-rich:
-
Cysteine rich
- DMAD:
-
DNA 6mA demethylase
- DNMT:
-
DNA methyltransferase
- DSBH:
-
Double-stranded β-helix
- E11.5:
-
Embryonic day 11.5
- FH:
-
Fumarate hydratase
- HCF1:
-
Host cell factor 1
- HEK293:
-
Human embryonic kidney 293
- hmU:
-
Hydroxymethyluracil
- IDH:
-
Isocitrate dehydrogenase
- iPSCs:
-
Induced pluripotent stem cells
- JBP:
-
J-binding protein
- JmjC:
-
Jumonji C
- LC-MS:
-
Liquid chromatography-mass spectrometry
- MEFs:
-
Mouse embryonic fibroblasts
- mESCs:
-
Mouse embryonic stem cells
- MET:
-
Mesenchymal to epithelial
- NER:
-
Nucleotide excision repair
- NOG:
-
N-oxalylglycine
- OGT:
-
O-linked β-N-acetylglucosamine transferase
- OSKM:
-
Oct4, Sox2, Klf4, and c-Myc
- PGCs:
-
Primordial germ cells
- Pol II:
-
RNA polymerase II
- R-2HG:
-
R-2-hydroxyglutarate
- SAM:
-
S-adenosyl methionine
- SDH:
-
Succinate dehydrogenase
- SMUG1:
-
Single-strand-selective monofunctional uracil DNA glycosylase 1
- T7H:
-
Thymine-7-hydroxylase
- TAB-seq:
-
Tet-assisted bisulfite sequencing
- TCA:
-
Tricarboxylic acid
- TDG:
-
Thymine-DNA glycosylase
- TET:
-
Ten-eleven translocation
- TSKM:
-
Tet1, Sox2, Kf4, and c-Myc
- TSS:
-
Transcription start site
- α-KG:
-
α-Ketoglutarate
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Acknowledgments
We thank Dr. Guoliang Xu and his lab members for critical reading of the manuscript. This work was supported by grants from the National Natural Science Foundation of China (31425008 and 91419301). We apologize that we could not cite many important papers due to space limitation.
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Yin, X., Xu, Y. (2016). Structure and Function of TET Enzymes. In: Jeltsch, A., Jurkowska, R. (eds) DNA Methyltransferases - Role and Function. Advances in Experimental Medicine and Biology, vol 945. Springer, Cham. https://doi.org/10.1007/978-3-319-43624-1_12
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