TET 蛋白和 5-羟甲基胞嘧啶在活性 DNA 去甲基化中的新兴作用及其他作用。
Emerging roles of TET proteins and 5-hydroxymethylcytosines in active DNA demethylation and beyond.
机构信息
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
出版信息
Cell Cycle. 2011 Aug 15;10(16):2662-8. doi: 10.4161/cc.10.16.17093.
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.
摘要
胞嘧啶甲基化是真核生物 DNA 的主要表观遗传修饰。尽管有强有力的证据表明，动物细胞中存在活跃的 DNA 去甲基化过程，但这一过程的分子细节尚不清楚。最近发现的 TET 蛋白家族（TET1-3）5-甲基胞嘧啶羟化酶为揭示长期寻求的 DNA 去甲基酶的身份提供了一个新的切入点。在这里，我们通过各种生化和基因组方法，综述了 TET 蛋白和 5-羟甲基胞嘧啶（5hmC）功能的最新研究进展，目前有证据表明 5hmC 是活跃 DNA 去甲基化的早期中间产物，以及 TET 蛋白和 5hmC 在活跃 DNA 去甲基化之外的潜在功能。我们还讨论了未来的研究如何扩展我们对这种新型表观遗传修饰的认识。
相似文献
1
Emerging roles of TET proteins and 5-hydroxymethylcytosines in active DNA demethylation and beyond.TET 蛋白和 5-羟甲基胞嘧啶在活性 DNA 去甲基化中的新兴作用及其他作用。
Cell Cycle. 2011 Aug 15;10(16):2662-8. doi: 10.4161/cc.10.16.17093.
2
GADD45a physically and functionally interacts with TET1.生长停滞和DNA损伤诱导蛋白45α（GADD45a）与TET1在物理和功能上相互作用。
Differentiation. 2015 Jul-Oct;90(1-3):59-68. doi: 10.1016/j.diff.2015.10.003. Epub 2015 Nov 3.
3
Role of ten-eleven translocation proteins and 5-hydroxymethylcytosine in hepatocellular carcinoma.十号十一号转位蛋白和 5-羟甲基胞嘧啶在肝细胞癌中的作用。
Cell Prolif. 2019 Jul;52(4):e12626. doi: 10.1111/cpr.12626. Epub 2019 Apr 29.
4
Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.维生素 C 诱导胚胎干细胞中的 Tet 依赖性 DNA 去甲基化和类囊胚状态。
Nature. 2013 Aug 8;500(7461):222-6. doi: 10.1038/nature12362. Epub 2013 Jun 30.
5
Tet family proteins and 5-hydroxymethylcytosine in development and disease.Tet 家族蛋白与 5-羟甲基胞嘧啶在发育和疾病中的作用。
Development. 2012 Jun;139(11):1895-902. doi: 10.1242/dev.070771.
6
Structural insight into substrate preference for TET-mediated oxidation.TET 介导的氧化反应底物偏好的结构见解。
Nature. 2015 Nov 5;527(7576):118-22. doi: 10.1038/nature15713. Epub 2015 Oct 28.
7
Tet family of 5-methylcytosine dioxygenases in mammalian development.哺乳动物发育中的 5-甲基胞嘧啶双加氧酶 Tet 家族。
J Hum Genet. 2013 Jul;58(7):421-7. doi: 10.1038/jhg.2013.63. Epub 2013 May 30.
8
TET1 promotes RXRα expression and adipogenesis through DNA demethylation.TET1 通过 DNA 去甲基化促进 RXRα 的表达和脂肪生成。
Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Jun;1866(6):158919. doi: 10.1016/j.bbalip.2021.158919. Epub 2021 Mar 6.
9
5-Hydroxymethylcytosine-mediated active demethylation is required for mammalian neuronal differentiation and function.5-羟甲基胞嘧啶介导的活性去甲基化对于哺乳动物神经元分化和功能至关重要。
Elife. 2021 Dec 17;10:e66973. doi: 10.7554/eLife.66973.
10
[Role of 5-hydroxymethylcytosine and TET proteins in epigenetic regulation of gene expression].5-羟甲基胞嘧啶和TET蛋白在基因表达表观遗传调控中的作用
Postepy Biochem. 2013;59(1):64-9.
引用本文的文献
1
5-Methylcytosine Methylation-Linked Hippo Pathway Molecular Interactions Regulate Lipid Metabolism.5-甲基胞嘧啶甲基化相关的 Hippo 信号通路分子相互作用调节脂质代谢。
Int J Mol Sci. 2025 Mar 12;26(6):2560. doi: 10.3390/ijms26062560.
2
Effects of hypoxia on uteroplacental and fetoplacental vascular function during pregnancy.孕期缺氧对子宫胎盘和胎儿胎盘血管功能的影响。
Front Physiol. 2024 Dec 18;15:1490154. doi: 10.3389/fphys.2024.1490154. eCollection 2024.
3
A core scientific problem in the treatment of central nervous system diseases: newborn neurons.中枢神经系统疾病治疗中的一个核心科学问题：新生神经元。
Neural Regen Res. 2024 Dec 1;19(12):2588-2601. doi: 10.4103/NRR.NRR-D-23-01775. Epub 2024 Apr 1.
4
Coordinated activation of DNMT3a and TET2 in cancer stem cell-like cells initiates and sustains drug resistance in hepatocellular carcinoma.癌症干细胞样细胞中DNMT3a和TET2的协同激活引发并维持肝细胞癌的耐药性。
Cancer Cell Int. 2024 Mar 25;24(1):110. doi: 10.1186/s12935-024-03288-3.
5
Pharmacologic Ascorbate and DNMT Inhibitors Increase DUOX Expression and Peroxide-Mediated Toxicity in Pancreatic Cancer.药理抗坏血酸盐和DNA甲基转移酶抑制剂可增加胰腺癌中DUOX的表达及过氧化物介导的毒性。
Antioxidants (Basel). 2023 Aug 29;12(9):1683. doi: 10.3390/antiox12091683.
6
Psoriatic Resolved Skin Epidermal Keratinocytes Retain Disease-Residual Transcriptomic and Epigenomic Profiles.银屑病消退皮肤表皮角质形成细胞保留疾病残留转录组和表观基因组特征。
Int J Mol Sci. 2023 Feb 25;24(5):4556. doi: 10.3390/ijms24054556.
7
Urinary Measurement of Epigenetic DNA Modifications and 8-oxodG as Possible Noninvasive Markers of Colon Cancer Evolution.尿液中表观遗传 DNA 修饰和 8-氧代脱氧鸟苷的测量作为结直肠癌演变的潜在非侵入性标志物。
Int J Mol Sci. 2022 Nov 10;23(22):13826. doi: 10.3390/ijms232213826.
8
Low expression of isocitrate dehydrogenase 1 (IDH1) R132H is associated with advanced pathological features in laryngeal squamous cell carcinoma.IDH1 R132H 低表达与喉鳞状细胞癌的晚期病理特征相关。
J Cancer Res Clin Oncol. 2023 Jul;149(8):4253-4267. doi: 10.1007/s00432-022-04336-z. Epub 2022 Sep 5.
9
Chemical and enzymatic modifications of 5-methylcytosine at the intersection of DNA damage, repair, and epigenetic reprogramming.5-甲基胞嘧啶的化学和酶修饰在 DNA 损伤、修复和表观遗传重编程的交汇点。
PLoS One. 2022 Aug 29;17(8):e0273509. doi: 10.1371/journal.pone.0273509. eCollection 2022.
10
Targeting Acute Myeloid Leukemia with Venetoclax; Biomarkers for Sensitivity and Rationale for Venetoclax-Based Combination Therapies.维奈托克治疗急性髓系白血病；敏感性生物标志物及基于维奈托克联合疗法的理论依据
Cancers (Basel). 2022 Jul 15;14(14):3456. doi: 10.3390/cancers14143456.
本文引用的文献
1
5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells.5-羟甲基胞嘧啶与人类胚胎干细胞中的增强子和基因体有关。
Genome Biol. 2011 Jun 20;12(6):R54. doi: 10.1186/gb-2011-12-6-r54.
2
Transcriptomic analysis of autistic brain reveals convergent molecular pathology.自闭症患者大脑的转录组分析揭示了趋同的分子病理学。
Nature. 2011 May 25;474(7351):380-4. doi: 10.1038/nature10110.
3
Tissue-specific distribution and dynamic changes of 5-hydroxymethylcytosine in mammalian genomes.哺乳动物基因组中 5-羟甲基胞嘧啶的组织特异性分布和动态变化。
J Biol Chem. 2011 Jul 15;286(28):24685-93. doi: 10.1074/jbc.M110.217083. Epub 2011 May 24.
4
Determination of genomic 5-hydroxymethyl-2'-deoxycytidine in human DNA by capillary electrophoresis with laser induced fluorescence.采用毛细管电泳激光诱导荧光法测定人 DNA 中的基因组 5-羟甲基-2'-脱氧胞苷。
Epigenetics. 2011 May;6(5):560-5. doi: 10.4161/epi.6.5.15678.
5
Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells.胚胎干细胞中 5-羟甲基胞嘧啶的全基因组图谱绘制。
Nature. 2011 May 19;473(7347):394-7. doi: 10.1038/nature10102. Epub 2011 May 8.
6
Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells.Tet1 羟化酶在小鼠胚胎干细胞中对 5hmC、5mC 和基因表达的全基因组调控。
Mol Cell. 2011 May 20;42(4):451-64. doi: 10.1016/j.molcel.2011.04.005. Epub 2011 Apr 21.
7
Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain.TET1 介导的 5-甲基胞嘧啶羟化促进成年大脑中的活性 DNA 去甲基化。
Cell. 2011 Apr 29;145(3):423-34. doi: 10.1016/j.cell.2011.03.022. Epub 2011 Apr 14.
8
TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity.TET1 和羟甲基胞嘧啶在转录和 DNA 甲基化保真度中的作用。
Nature. 2011 May 19;473(7347):343-8. doi: 10.1038/nature10066. Epub 2011 Apr 13.
9
Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation.小鼠胚胎干细胞及其分化过程中 5-羟甲基胞嘧啶的动态调控
Nature. 2011 May 19;473(7347):398-402. doi: 10.1038/nature10008. Epub 2011 Apr 3.
10
Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells.全基因组分析 5-羟甲基胞嘧啶的分布揭示了其在小鼠胚胎干细胞转录调控中的双重功能。
Genes Dev. 2011 Apr 1;25(7):679-84. doi: 10.1101/gad.2036011.
Zotero 插件