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Role of TET enzymes in DNA methylation, development, and cancer
Open accessAbstract
The pattern of DNA methylation at cytosine bases in the genome is tightly linked to gene expression, and DNA methylation abnormalities are often observed in diseases. The ten eleven translocation (TET) enzymes oxidize 5-methylcytosines (5mCs) and promote locus-specific reversal of DNA methylation. TET genes, and especially TET2 , are frequently mutated in various cancers, but how the TET proteins contribute to prevent the onset and maintenance of these malignancies is largely unknown. Here, we highlight recent advances in understanding the physiological function of the TET proteins and their role in regulating DNA methylation and transcription. In addition, we discuss some of the key outstanding questions in the field.
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“Generally, 2OGO catalyze specific hydroxylation of substrates, which, in turn, leads to demethylations via other catalytic cycles or downstream pathway involving thymine-DNA-glycosylase, which catalyzed base excision with DNA base excision repair [101,120].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [120]
Experimental — accuracy not yet measuredIn the citing paper
“TET2 is frequently mutated or lost somatically in both myeloid and lymphoid malignancies63,64.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [63]
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“Thus, it was remarkable when ten eleven translocation protein 1 (TET1) was discovered and shown to be able to modify methylcytosine and potentially erase DNAmethylation (Tahiliani et al. 2009).”
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“Second, TET2 mutations are frequently observed in aged healthy individuals with clonal hematopoiesis and increase the propensity to develop hematopoieticmalignancies (Busque et al. 2012; Genovese et al. 2014; Jaiswal et al. 2014; Xie et al. 2014).”
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“Subsequent to the discovery of oxidized 5mC bases, it was demonstrated that TDG has no effect on 5hmC but shows robust recruitment and in vitro catalytic activity toward 5fC and 5caC (He et al. 2011; Maiti and Drohat 2011; Spruijt et al. 2013).”
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“By comparison, the products of further TET-mediated oxidation, 5fC and 5caC, are observed at ∼10-fold to 100-fold lower levels than 5hmC and often close to or under the detection limit (Kriaucionis and Heintz 2009; Globisch et al. 2010; Szwagierczak et al. 2010; He et al. 2011; Ito et al. 2011; Pfaffeneder et al. 2011…”
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“These, in turn, affect several critical genes that have pivotal roles in epigenetic control, including the ten-eleven translocations (TET 1,2,3) and JMJC families, which are often altered or transcriptionally downregulated in hematological [176,177] and solid malignancies [178].”
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“In contrast, the ten-eleven translocation (TET) enzyme is associated with DNA demethylation by reactivating the expression of the silenced gene (34).”
BackgroundHypoxia and Oxygen-Sensing Signaling in Gene Regulation and Cancer Progression
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“Physiologically, Tet3 is critical for embryonic development [130], and Tet1 and Tet2 are important for hematopoietic cell differentiation [132].”
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The YTHDF proteins display distinct cellular functions on m6A-modified RNA
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“5mC and 5hmC together make up the bulk of methylated DNA with other oxidative products such as 5-formyl cytosine (5fC) and 5-carboxyl cytosine (5caC) being an order of magnitude less abundant [78].”
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Pan, X., & Zheng, L. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-0505-9 · Cited by 79
“TETs play important roles in several solid tumors, in which loss of function promotes aberrant DNA methylation.(68) Loss of 5-hmC regulated by TETs has been reported as an epigenetic hallmark of melanoma.”
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Epigenetics in prostate cancer: clinical implications
Conteduca, V., Hess, J., Yamada, Y., Ku, S., & Beltran, H. (2021) · Translational Andrology and Urology · doi:10.21037/tau-20-1339 · Cited by 79
“DNA methyltransferase enzymes catalyze the addition of methyl groups to cytosine residues in DNA to form 5-methyl cytosine (5mC), which can be deleted by the TET family of DNA demethylases (16).”
BackgroundA Positive Feedback Loop of TET3 and TGF-β1 Promotes Liver Fibrosis
Xu, Y., Sun, X., Zhang, R., Cao, T., Cai, S.-Y., Boyer, J. L., Zhang, X., Li, D., & Huang, Y. (2020) · Cell Reports · doi:10.1016/j.celrep.2019.12.092 · Cited by 73
“The TET proteins belong to a novel class of DNA demethylases that oxidize 5methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), which is subsequently converted to unmethylated cytosine (An et al., 2017; Rasmussen and Helin, 2016; Wu and Zhang, 2017).”
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“Given these findings and the evidence that genomic 5hmC can sometimes be a long-lived intermediate in demethylation of 5mC residues.(5) We looked for a relationship between 5mC in Figure 1.”
BackgroundResultInfluentialUnderstanding the Therapeutic Potential of Ascorbic Acid in the Battle to Overcome Cancer
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“Mutation and altered expression of ten-eleven translocation (TET) protein families [45] lead to abnormal DNA methylation, which contributes to cancer formation [58].”
BackgroundDeng, Y., Shi, M., Lin, Y., Khan, M. N., Xia, Z., & Li, X. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e37060 · Cited by 73
“The ten-eleven translocation (TET) enzymes, which function as 5-methylcytosine oxidases, can reverse locus-specific methylation [32].”
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Huilgol, D., Venkataramani, P., Nandi, S., & Bhattacharjee, S. (2019) · Genes · doi:10.3390/genes10100794 · Cited by 75
“Ten eleven translocation (TET) enzymes are multi-domain enzymes, important for regulating DNA methylation [62].”
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Bhootra, S., Jill, N., Shanmugam, G., Rakshit, S., & Sarkar, K. (2023) · Medical Oncology · doi:10.1007/s12032-022-01943-1 · Cited by 79
“Few models have suggested that TFs that are insensitive or bind to mCpGs were shown to induce active demethylation TETs [55].”
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“The role of TET2 in tumor resistance is not well studied, but the upregulation of TET3 has been shown to increase the expression of tumor suppressor genes, leading to the inhibition of growth and self-renewal ability in glioblastoma stem cells [459].”
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“10 of 22 TET1 and TET3 possess an N-terminal CXXC domain, which can directly associate with DNA and ensure the recruitment of the protein to target genomic sites [123]. domain (Figure 2) [7].”
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Reprogramming: identifying the mechanisms that safeguard cell identity
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Introduction to Single-Cell DNA Methylation Profiling Methods
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“TET enzymes sequentially convert methylated cytosines into hydroxymethyl cytosines, formyl cytosines, and carboxyl cytosines [110].”
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“Conversely, the ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine, promoting the reversal of DNA methylation and gene silencing [31].”
BackgroundRecent Advances in Epigenetic Biomarkers and Epigenetic Targeting in Prostate Cancer
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“On the other hand, impaired functions of demethylation enzymes such as ten eleven translocation (TET); TET2 and TET3 are associated with cell transformation and cancer progression.(11) Recently, we have reported that in primary breast cancer (PBC), the transcriptomic expression of ICs including PD-1, CTLA-4, LAG-3 and…”
BackgroundDegradation of 5hmC-marked stalled replication forks by APE1 causes genomic instability
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“Given that TET proteins are involved in DNA demethylation, they regulate various cellular processes such as gene expression and cell differentiation (28).”
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Mulholland, C. B., Nishiyama, A., Ryan, J., Nakamura, R., Yiğit, M., Glück, I. M., Trummer, C., Qin, W., Bartoschek, M. D., Traube, F. R., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19603-1 · Cited by 74
Oxygen regulation of TET enzymes
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Selective targeting of TET catalytic domain promotes somatic cell reprogramming
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“DNA methylation serves as a signal for the recruitment of epigenetic modifiers affecting the histone code or chromatin remodeling factors and often has a repressive effect [13,14].”
BackgroundSnail/PRMT5/NuRD complex contributes to DNA hypermethylation in cervical cancer by TET1 inhibition
Gao, J., Liu, R., Feng, D., Huang, W., Huo, M., Zhang, J., Leng, S., Yang, Y., Yang, T., Yin, X., et al. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-021-00786-z · Cited by 65
TET-Mediated Epigenetic Regulation in Immune Cell Development and Disease
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Tackling PARP inhibitor resistance
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Hinokitiol induces DNA demethylation via DNMT1 and UHRF1 inhibition in colon cancer cells
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“(JPG 102 kb) Abbreviations 5-aza-dC: 5-aza-2′-deoxycytidine; 5-hmC: 5-hydroxymethylcytosine; 5-mC: 5- methylacytosine; AKR1B1: Aldo-keto reductase 1; BTG4: B-cell translocation gene 4; CHST10: carbohydrate sulfotransferase 10; CpG: Cytosine-phosphateguanine; DMSO: Dimethyl sulfoxide; DNMT: DNA methyltransferease; ELOV…”
InfluentialTET-Mediated Sequestration of miR-26 Drives EZH2 Expression and Gastric Carcinogenesis
Deng, M., Zhang, R., He, Z., Qiu, Q., Lu, X., Yin, J., Liu, H., Jia, X., & He, Z. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2964 · Cited by 63
Epigenetic Reprogramming of TGF-β Signaling in Breast Cancer
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“This process is counteracted by a family of enzymes called the Ten-eleven translocation (TET) enzymes [29].”
BackgroundDual mechanisms of posttranscriptional regulation of Tet2 by Let-7 microRNA in macrophages
Jiang, S., Yan, W., Wang, S. E., & Baltimore, D. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1811040116 · Cited by 63
“Presumably, the effects on Tet2 levels caused by let-7adf and succinate cause alterations in DNA methylation, the only known effect of Tet2 (23, 24).”
BackgroundDeciphering DNA methylation signatures of pancreatic cancer and pancreatitis
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Targeting the epigenome in in-stent restenosis: from mechanisms to therapy
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“Recently, the roles of TET in various diseases, particularly in cancer, were investigated extensively.(38) In addition, downregulation of TET2 was observed in human atherosclerotic samples and in a mouse femoral artery wire injury model.”
BackgroundThe role of vitamin C in epigenetic cancer therapy
Mikkelsen, S. U., Gillberg, L., Lykkesfeldt, J., & Grønbæk, K. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.03.017 · Cited by 62
TET2 Suppresses VHL Deficiency-Driven Clear Cell Renal Cell Carcinoma by Inhibiting HIF Signaling
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DNA methylation regulated gene expression in organ fibrosis
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“5hmC is considered an intermediate in an active demethylation process catalyzed by the ten-eleven translocation (TET) family, which comprises three members, TET1 to TET3, that have combinatory roles in different developmental process as well as carcinogenesis (13).”
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“Low levels of TET1 are associated with tumor aggressiveness, recurrence, and adverse prognosis (Rasmussen & Helin, 2016).”
BackgroundRetractedGoronzy, J. J., Hu, B., Kim, C., Jadhav, R. R., & Weyand, C. M. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.1ri0418-160r · Cited by 60
The Application of Genome-Wide 5-Hydroxymethylcytosine Studies in Cancer Research
Thomson, J. P., & Meehan, R. R. (2016) · Epigenomics · doi:10.2217/epi-2016-0122 · Cited by 60
Cytokine-Regulated Phosphorylation and Activation of TET2 by JAK2 in Hematopoiesis
Jeong, J. J., Gu, X., Nie, J., Sundaravel, S., Liu, H., Kuo, W.-L., Bhagat, T. D., Pradhan, K., Cao, J. Z., Nischal, S., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1138 · Cited by 64
“Epigenetic changes including DNA cytosine methylation and hydroxymethylation play important roles in regulating differentiation of hematopoietic cells into committed progeny (1-3).”
BackgroundShi, F., Zhou, M., Li, S., Du, Q., Li, Y., Xie, L., Liu, X., Tang, M., Luo, X., Fan, J., et al. (2019) · Theranostics · doi:10.7150/thno.30941 · Cited by 58
“Decreased expression/ or activity of TETs and low levels of 5-hmC are hallmarks of various cancers [38, 39].”
BackgroundCalcium regulation of stem cells
Snoeck, H. (2020) · EMBO Reports · doi:10.15252/embr.202050028 · Cited by 59
“The three TET homologues convert 5-methylcytosine (5mC) to 5-hydroxymethyl cytosine (5hmC) [132,133].”
Transcriptional programs that control expression of the autoimmune regulator gene Aire
Herzig, Y., Nevo, S., Bornstein, C., Brezis, M. R., Ben‐Hur, S., Shkedy, A., Eisenberg‐Bord, M., Levi, B. Z., Delacher, M., Goldfarb, Y., et al. (2016) · Nature Immunology · doi:10.1038/ni.3638 · Cited by 57
Mechanisms of chromatin-based epigenetic inheritance
Du, W., Shi, G., Shan, C., Li, Z., Zhu, B., Jia, S., Li, Q., & Zhang, Z. (2022) · Science China Life Sciences · doi:10.1007/s11427-022-2120-1 · Cited by 53
“In addition, many regulatory elements used to control gene expression are largely resistant to CpG methylation (Hon et al., 2013; Ziller et al., 2013; Rasmussen and Helin, 2016).”
BackgroundZhong, F., Lin, Y., Zhao, L., Yang, C., Ye, Y., & Shen, Z. (2023) · British Journal of Cancer · doi:10.1038/s41416-023-02292-0 · Cited by 58
“, more or less participate in the deregulation of TET proteins, and the detailed mechanisms have been reviewed elsewhere [30, 31].”
BackgroundZhu, D., Zeng, S., Su, C., Li, J., Xuan, Y., Lin, Y., Xu, E., & Fan, Q. (2024) · Clinical Epigenetics · doi:10.1186/s13148-024-01633-x · Cited by 57
Opportunities for Therapeutic Modulation of O-GlcNAc
Cheng, S. S., Mody, A. C., & Woo, C. M. (2024) · Chemical Reviews · doi:10.1021/acs.chemrev.4c00417 · Cited by 64
Expression and prognosis analysis of DNMT family in acute myeloid leukemia
Zhang, T., Zhang, L.-C., Xu, Z., & Zhou, J. (2020) · Aging · doi:10.18632/aging.103520 · Cited by 54
Decoding the Rosetta stone of mitonuclear communication
English, J., Son, J. M., Cardamone, M. D., Lee, C., & Perissi, V. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105161 · Cited by 55
“Prior to this step, ten-eleven translocation (TET) enzymes oxidize 5mC to 5-hydroxymethylcytosine (5hmC) in a process that requires mitochondrialproduced α-KG, Fe(II), and oxygen (O2), and can be inhibited by fumarate, succinate, and 2-hydroxyglutarate (2-HG) (Etchegaray and Mostoslavsky, 2016; Pastor et al., 2013; Ra…”
BackgroundLeveraging epigenetics to enhance the efficacy of immunotherapy
Licht, J. D., & Bennett, R. L. (2021) · Clinical Epigenetics · doi:10.1186/s13148-021-01100-x · Cited by 54
“DNA demethylation is expedited by the TET enzymes which convert methyl cytosine into hydroxymethylcytosine, a base modification not recognized by DNMT1 [9].”
BackgroundThe Epigenetic Role of Vitamin C in Neurodevelopment
Coker, S. J., Smith-Díaz, C. C., Dyson, R. M., Vissers, M. C. M., & Berry, M. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031208 · Cited by 57
“Changes in chromatin states may influence gene expression, imparting cell-specific transcription programs that allow cells to become phenotypically different from each other [56].”
BackgroundWu, R., Sun, C., Chen, X., Yang, R., Luan, Y., Zhao, X., Yu, P., Luo, R., Hou, Y., Tian, R., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2321611121 · Cited by 56
“TET2 is a well - known DNA m5C dioxygenase (22), which can decrease the level of caRNA by converting m5C to 5hmC (5).”
BackgroundTET2 : A Novel Epigenetic Regulator and Potential Intervention Target for Atherosclerosis
Liu, Y., Peng, W., Qu, K., Lin, X., Zeng, Z., Chen, J., Wei, D., & Zuo, W. (2018) · DNA and Cell Biology · doi:10.1089/dna.2017.4118 · Cited by 56
“The roles of TET in diseases, especially in cancer, have been widely studied in recent years (Rasmussen and Helin, 2016).”
BackgroundIdentification of DNA motifs that regulate DNA methylation
Wang, M., Zhang, K., Ngo, V., Liu, C., Fan, S., Whitaker, J. W., Chen, Y., Ai, R., Chen, Z., Wang, J., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz483 · Cited by 57
“Furthermore, TET prefers CpG-rich patterns such as CpG island which spans several kilobases (66) and can bind CpG-rich DNA sequences (62) in mammalians to maintain stable demethylation (67); consistently, UMs have significantly higher GC content than MMs and known motifs (P < 0.”
BackgroundHuang, Z., Yu, J., Cui, W., Johnson, B. K., Kim, K., & Pfeifer, G. P. (2021) · Science Advances · doi:10.1126/sciadv.abb9149 · Cited by 54
“We found that the C-terminal double-stranded -helix domain of TET3, which represents the core catalytic region conserved between all three TET proteins ( 8 , 20 , 34 ), interacts strongly with SMCHD1 (Fig.”
Epigenetics-based therapeutics for myocardial fibrosis
Li, X., Yang, Y., Chen, S., Zhou, J., Li, J., & Cheng, Y. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119186 · Cited by 55
Mechanisms of DNA Methylation Regulatory Function and Crosstalk with Histone Lysine Methylation
Tibben, B. M., & Rothbart, S. B. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168394 · Cited by 61
Kaltsas, A., Markou, E., Kyrgiafini, M.-A., Zikopoulos, A., Symeonidis, E. N., Dimitriadis, F., Zachariou, A., Sofikitis, N., & Chrisofos, M. (2025) · Genes · doi:10.3390/genes16010093 · Cited by 63
“ROS also affect DNA demethylation by interfering with Ten-eleven translocation (TET) enzymes, which oxidize 5-methylcytosine to facilitate active demethylation [49].”
Epigenetic regulation of cancer-associated fibroblast heterogeneity
Kehrberg, R. J., Bhyravbhatla, N., Batra, S. K., & Sushil Kumar, K. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188901 · Cited by 57
Charras, A., Arvaniti, P., Dantec, C. L., Arleevskaya, M. I., Zachou, K., Dalekos, G. Ν., Bordron, A., & Renaudineau, Y. (2019) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-019-08743-y · Cited by 53
Rosikiewicz, W., Chen, X., Domínguez, P. M., Ghamlouch, H., Aoufouchi, S., Bernard, O., Melnick, A. M., & Li, S. (2020) · Science Advances · doi:10.1126/sciadv.aay5872 · Cited by 61
“Although DLBCLs arise from mature GC B cells, they seem to inherit TET2 mutations from hematopoietic stem cells (HSCs), which can give rise to additional hematologic malignancies harboring the same TET2 allele (15, 45).”
BackgroundDeciphering the genetic code of DNA methylation
Wang, M., Ngo, V., & Wang, W. (2020) · Briefings in Bioinformatics · doi:10.1093/bib/bbaa424 · Cited by 54
“Locus-specific DNA methylation or demethylation depends on the recruitment of specific enzymes such as TET and DNMTs to the target genomic regions [6–8] (Figure 1A).”
BackgroundInfluentialTET2 directs mammary luminal cell differentiation and endocrine response
Kim, M. R., Wu, M., Zhang, Y., Yang, J., & Chang, C. J. (2020) · Nature Communications · doi:10.1038/s41467-020-18129-w · Cited by 52
Epigenomic and enhancer dysregulation in uterine leiomyomas
Mlodawska, O. W., Saini, P., Parker, J. B., Wei, J., Bulun, S. E., Simon, M. A., & Chakravarti, D. (2022) · Human Reproduction Update · doi:10.1093/humupd/dmac008 · Cited by 54
Epigenetic Dysregulations in Arsenic-Induced Carcinogenesis
Islam, R., Zhao, L., Wang, Y.-F., Lu-Yao, G. L., & Liu, L.-Z. (2022) · Cancers · doi:10.3390/cancers14184502 · Cited by 55
“DNA methylation inhibition occurs in a site-specific manner by proteins known as the ten-eleven translocation (TET) enzymes [63,64].”
BackgroundAssessing the Impact of Polyethylene Nano/Microplastic Exposure on Human Vaginal Keratinocytes
Pontecorvi, P., Ceccarelli, S., Cece, F., Camero, S., Lotti, L. V., Niccolai, E., Nannini, G., Gerini, G., Anastasiadou, E., Scialis, E. S., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411379 · Cited by 57
“The Ten eleven translocation (TET) enzymes oxidise 5-methylcytosines (5mCs) and promote locus-specific reversal of DNA methylation [41].”
BackgroundGuo, X. H., Zhong, J., Zhao, Y., Fu, Y., Sun, L., Yuan, A., Liu, J., Chen, A. F., & Pu, J. (2024) · Circulation · doi:10.1161/circulationaha.123.065202 · Cited by 51
“7 Accumulating studies have provided convincing evidence of the correlation between AAA and aberrant DNA methylation; however, limited studies have investigated the mechanism of DNA methylation in AAA.”
BackgroundXu, Y., Yang, Y., Wang, Z., Sjöström, M., Jiang, Y., Tang, Y., Cheng, S., Deng, S., Wang, C., Gonzalez, J., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0539 · Cited by 50
“Among those three validated resistance drivers, the epigenetic and 5hmC modifier, TET2, plays a critical role in cell fate and lineage decision during both normal development and carcinogenesis (27–29 , 40 ).”
Epigenetics: from the past to the present
Villota-Salazar, N. A., Mendoza‐Mendoza, A., & González-Prieto, J. M. (2016) · Frontiers in Life Science · doi:10.1080/21553769.2016.1249033 · Cited by 55
“There is not yet enough evidence to support the hypothesis that 5hmC, 5fC and 5caC could be new epigenetic marks (Rasmussen & Helin 2016).”
BackgroundPoole, C. J., Lodh, A., Choi, J.-H., & van Riggelen, J. (2019) · Epigenetics & Chromatin · doi:10.1186/s13072-019-0278-5 · Cited by 52
Waheed, S. O., Chaturvedi, S. S., Karabencheva‐Christova, T. G., & Christov, C. Z. (2021) · ACS Catalysis · doi:10.1021/acscatal.0c05034 · Cited by 49
UV Radiation and Its Relation to DNA Methylation in Epidermal Cells: A Review
de Oliveira, N. F. P., de Souza, B. F., & Coêlho, M. D. C. (2020) · Epigenomes · doi:10.3390/epigenomes4040023 · Cited by 51
“They catalyze demethylation reactions by oxidation of 5-mC and promote locus-specific reversion of methylation [1,5].”
BackgroundInfluentialJabeen, M., Fayyaz, M., & Irudayaraj, J. (2020) · Toxics · doi:10.3390/toxics8040112 · Cited by 52
“DNA methylation is characterized by the addition of the methyl (-CH3) group to the cytosine guanine dinucleotides (CpG) sites of DNA, which is highly organized and regulated by two groups of enzymes: DNA methyltransferases (DNMTs) [64] and Ten-eleven translocation (TETs) [65] enzymes.”
BackgroundMetabolic reprogramming of T regulatory cells in the hypoxic tumor microenvironment
Nair, V. S., Saleh, R., Toor, S. M., Cyprian, F. S., & Elkord, E. (2021) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-020-02842-y · Cited by 51
Broome, R., Chernukhin, I. V., Jamieson, S., Kishore, K., Papachristou, E. K., Mao, S.-Q., Tejedo, C. G., Mahtey, A., Theodorou, V., Groen, A. J., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108776 · Cited by 50
“In contrast to TET1 and TET3, which tend to bind to promoter proximal regions (Jin et al., 2016; Rasmussen et al., 2015; Rasmussen and Helin, 2016; Williams et al., 2011), the preference of TET2 for enhancers supports the conclusion that TET2 recruitment involves cell-specific transcription factors (Wang et al.”
BackgroundBraný, D., Dvorská, D., Strnádel, J., Matáková, T., Halášová, E., & Škovierová, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212252 · Cited by 56
Epigenetic Alterations under Oxidative Stress in Stem Cells
Huang, M., Wu, Q., & Jiang, Z. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/6439097 · Cited by 50
“Interestingly, the TET proteins can successively oxidize 5-methylcytosine (5-mc) to 5-hydroxymethylcytosine (5-hmC) [81] as a resultant of demethylation of CpG site mod-i fi cation [82] and subsequently into 5-formylcytosine and 5-carboxylcytosine [83].”
Epigenetic remodeling of the immune landscape in cancer: therapeutic hurdles and opportunities
Tien, F., Lu, H., Lin, S., & Tsai, H.-C. (2023) · Journal of Biomedical Science · doi:10.1186/s12929-022-00893-0 · Cited by 51
“By contrast, TETs (Ten-eleven translocation enzymes), also known as methylcytosine dioxygenases, facilitate passive and active DNA demethylation by catalyzing 5-methylcytosine oxidation to produce 5-hydroxymethylcytosine (5hmC) and other methylcytosine metabolites [21].”
Background
Metadata
- Authors
- Rasmussen, K. D., & Helin, K.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Helin, Kristian
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2016-04-01
- Volume
- 30
- Issue
- 7
- Pages
- 733-750
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC4826392
- OpenAlex
- W2325267338
- Cited by
- 1,040
- References
- 162
- Citations by year
- 2026: 56 · 2025: 87 · 2024: 116 · 2023: 100 · 2022: 135 · 2021: 141 · 2020: 131 · 2019: 97 · 2018: 83 · 2017: 60 · 2016: 30
- Type
- posted content
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Genes & Development (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Danish Medical Research Council (1333-00120B)
- European Research Council (294666_DNAMET)
- Danish Cancer Society
- Danish National Research Foundation (DNRF 82)
- Danish Council for Strategic Research
- Novo Nordisk Foundation
- 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 › Cancer-related gene regulation
- Keywords
- TET enzymes, DNA methylation, 5-methylcytosine oxidation, TET2, demethylation, cancer, developmental regulation, transcriptional regulation, gene expression
- MeSH terms
- Animals, Cytosine, DNA-Binding Proteins, Humans, Neoplasms, Oxidation-Reduction, Proto-Oncogene Proteins, Gene Expression Regulation, Neoplastic, DNA Methylation, Epigenesis, Genetic, Dioxygenases
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