IMR Press / FBL / Volume 26 / Issue 10 / DOI: 10.52586/4996
Open Access Review
Ten-eleven translocation proteins (TETs): tumor suppressors or tumor enhancers?
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1 Department of Internal Medicine, Qingdao Agricultural University Associated Hospital, 266109 Qingdao, Shandong, China
2 Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA
3 Department of Psychology Clinic, Qingdao Central Hospital, 266042 Qingdao, Shandong, China
4 Department of Neurology and Department of Nutrition, The Second Hospital Cheeloo College of Medicine, Shandong University, 250033 Jinan, Shandong, China
Front. Biosci. (Landmark Ed) 2021, 26(10), 895–915; https://doi.org/10.52586/4996
Submitted: 28 April 2021 | Revised: 1 September 2021 | Accepted: 8 September 2021 | Published: 30 October 2021
Copyright: © 2021 The Author(s). Published by BRI.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Abstract

The epigenetic memory stored in the dynamic modifications, such as base modifications of cytosine (C) in DNA, including methylation/hydroxymethylation/demethylation, causes heritable phenotypes via regulating gene expression without alteration of DNA sequence. The process from cytosine modification to the epigenetic effect is orchestrated by complicated machinery consisting of writers, erasers, readers, and other factors. The two major forms of cytosine modification include methylcytosine (5-mC) and hydroxymethylcytosine (5-hmC). DNA methyltransferases (DNMTs) including DNMT1, DNMT3A, and DNMT3B function as writers for 5-mC. The ten-eleven translocation proteins (TET) including TET1, TET2, and TET3 in the mammalian genome are responsible for hydroxymethylation of 5-mC to generate 5-hmC, 5-formylcytosine (5-fC), and 5-carboxylcytosine (5-caC). The 5-mC and 5-hmC have become the two most extensively investigated epigenetic markers, and the dynamic balance of these two markers shape the landscape of the epigenome, functioning as a platform to regulate gene expression epigenetically. The landscape of the 5-hmC in epigenome is precisely and tightly regulated during the development. Aberrant alterations of the epigenetic regulation may cause severe consequences such as phenotype change as well as initiation of disease. Progressively, significant achievements have been made in characterization of writers, erasers, and readers of 5-mC and 5-hmC, as well as the contribution of aberrant alteration of 5-hmC/5-mC landscape to the pathogenesis of human diseases, such as cancers and neurological disorders. This article will highlight the research advances in the distinct contribution of TET proteins as suppressors or promoters to the pathogenesis of tumorigenesis and progression. Furthermore, this article also discusses the challenges and the directions for research in the future.

Keywords
Ten-eleven translocation proteins
Epigenetics
5-hydroxymethylcytosine
5-methycytosine
Landscape
Cancer
Repressor
Promoter
Non-coding RNA
Figures
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