Description
TET1 (Ten-eleven translocation 1), also called methylcytosine dioxygenase TET1 or CXXC6, is one of three members of the human TET protein family of alpha-ketoglutarate oxygenases which includes TET2 and TET3 (1-3). TET1 is an enzyme that plays a role in epigenetic regulation of DNA methylation by conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), and further to 5-formylcystosine (5fC) and 5-carboxylcystosine (5caC) (1-5). The human TET1 protein is 2136 amino acids in length with a theoretical molecular weight of 235 kDa (6). Primary features of the TET1 protein include an N-terminal CXXC domain responsible for binding CpG islands in DNA, and a C-terminal catalytic domain containing a Cys-rich region followed by a double-stranded beta-helix (DSBH) domain that contributes to the mC dioxygenase activity and metal binding (1,2,4,5).
Recent studies have shown a role for TET1 in mediating epigenetic changes, such as DNA methylation status, in response to environmental factors such as food and nutrition, exercise, radiation, and allergens (3). The balance between DNA methylation and demethylation is crucial in health and homeostasis (3,5). In addition to response to environmental exposures, TET1 also plays a role in different diseases and cancer subtypes where it can function as either a tumor suppressor or tumor promoter (2,5). TET1 was originally identified as a fusion partner for the mixed lineage leukemia (MLL) gene in acute myeloid leukemia (AML) (1-3). While TET1 expression is low in AML, it is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL) (2). Similarly, TET1 expression is suppressed in hormone receptor positive breast cancer (HRBC) but elevated in triple negative breast cancer (2). TET1 is a potential therapeutic target in certain cancers, but due to its complex role in different signaling pathways its potential needs to be more widely studied (2). While TET1 is primarily responsible for initiating DNA demethylation, it also functions alongside 5hmc in maintaining pluripotency in embryonic stem cells (ESCs) and can serve as a marker for differentiation (1,2,4,5).
References
1. Tan L, Shi YG. Tet family proteins and 5-hydroxymethylcytosine in development and disease. Development. 2012;139(11):1895-1902. https://doi.org/10.1242/dev.070771
2. Liu W, Wu G, Xiong F, Chen Y. Advances in the DNA methylation hydroxylase TET1. Biomark Res. 2021;9(1):76. https://doi.org/10.1186/s40364-021-00331-7
3. Zhu T, Brown AP, Ji H. The Emerging Role of Ten-Eleven Translocation 1 in Epigenetic Responses to Environmental Exposures. Epigenet Insights. 2020;13:2516865720910155. https://doi.org/10.1177/2516865720910155
4. Melamed P, Yosefzon Y, David C, Tsukerman A, Pnueli L. Tet Enzymes, Variants, and Differential Effects on Function. Front Cell Dev Biol. 2018;6:22. https://doi.org/10.3389/fcell.2018.00022
5. Ma C, Seong H, Liu Y, Yu X, Xu S, Li Y. Ten-eleven translocation proteins (TETs): tumor suppressors or tumor enhancers?. Front Biosci (Landmark Ed). 2021;26(10):895-915. https://doi.org/10.52586/4996
6. Uniprot (Q8NFU7)
Bioinformatics
| Entrez |
Mouse
Human
|
| Uniprot |
Human
|
| Product By Gene ID |
80312 |
| Alternate Names |
- bA119F7.1
- CXXC finger 6
- CXXC6
- CXXC6FLJ10839
- FLJ41442
- KIAA1676CXXC-type zinc finger protein 6
- LCX
- LCXEC 1.14.11.n2
- Leukemia-associated protein with a CXXC domain
- methylcytosine dioxygenase TET1
- Ten-eleven translocation 1 gene protein
- ten-eleven translocation-1
- tet oncogene 1
|
