» Articles » PMID: 21811096

Emerging Roles of TET Proteins and 5-hydroxymethylcytosines in Active DNA Demethylation and Beyond

Overview
Journal Cell Cycle
Specialty Cell Biology
Date 2011 Aug 4
PMID 21811096
Citations 111
Authors
Affiliations
Soon will be listed here.
Abstract

Cytosine methylation is the major epigenetic modification of metazoan DNA. Although there is strong evidence that active DNA demethylation occurs in animal cells, the molecular details of this process are unknown. The recent discovery of the TET protein family (TET1-3) 5-methylcytosine hydroxylases has provided a new entry point to reveal the identity of the long-sought DNA demethylase. Here, we review the recent progress in understanding the function of TET proteins and 5-hydroxymethylcytosine (5hmC) through various biochemical and genomic approaches, the current evidence for a role of 5hmC as an early intermediate in active DNA demethylation and the potential functions of TET proteins and 5hmC beyond active DNA demethylation. We also discuss how future studies can extend our knowledge of this novel epigenetic modification.

Citing Articles

Effects of hypoxia on uteroplacental and fetoplacental vascular function during pregnancy.

Arenas G, Lorca R Front Physiol. 2025; 15:1490154.

PMID: 39744703 PMC: 11688409. DOI: 10.3389/fphys.2024.1490154.


A core scientific problem in the treatment of central nervous system diseases: newborn neurons.

Hao P, Yang Z, So K, Li X Neural Regen Res. 2024; 19(12):2588-2601.

PMID: 38595278 PMC: 11168522. DOI: 10.4103/NRR.NRR-D-23-01775.


Coordinated activation of DNMT3a and TET2 in cancer stem cell-like cells initiates and sustains drug resistance in hepatocellular carcinoma.

Cheng T, Zhou C, Bian S, Sobeck K, Liu Y Cancer Cell Int. 2024; 24(1):110.

PMID: 38528605 PMC: 10962188. DOI: 10.1186/s12935-024-03288-3.


Pharmacologic Ascorbate and DNMT Inhibitors Increase DUOX Expression and Peroxide-Mediated Toxicity in Pancreatic Cancer.

Steers G, OLeary B, Du J, Wagner B, Carroll R, Domann F Antioxidants (Basel). 2023; 12(9).

PMID: 37759986 PMC: 10525653. DOI: 10.3390/antiox12091683.


Psoriatic Resolved Skin Epidermal Keratinocytes Retain Disease-Residual Transcriptomic and Epigenomic Profiles.

Ghaffarinia A, Ayaydin F, Poliska S, Manczinger M, Bolla B, Flink L Int J Mol Sci. 2023; 24(5).

PMID: 36901987 PMC: 10002496. DOI: 10.3390/ijms24054556.


References
1.
Wu H, DAlessio A, Ito S, Wang Z, Cui K, Zhao K . Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells. Genes Dev. 2011; 25(7):679-84. PMC: 3070931. DOI: 10.1101/gad.2036011. View

2.
Liutkeviciute Z, Lukinavicius G, Masevicius V, Daujotyte D, Klimasauskas S . Cytosine-5-methyltransferases add aldehydes to DNA. Nat Chem Biol. 2009; 5(6):400-2. DOI: 10.1038/nchembio.172. View

3.
Ito S, DAlessio A, Taranova O, Hong K, Sowers L, Zhang Y . Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature. 2010; 466(7310):1129-33. PMC: 3491567. DOI: 10.1038/nature09303. View

4.
Day J, Sweatt J . DNA methylation and memory formation. Nat Neurosci. 2010; 13(11):1319-23. PMC: 3130618. DOI: 10.1038/nn.2666. View

5.
PENN N, SUWALSKI R, ORiley C, Bojanowski K, YURA R . The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid. Biochem J. 1972; 126(4):781-90. PMC: 1178489. DOI: 10.1042/bj1260781. View