TET-mediated active DNA demethylation: mechanism, function and beyond

被引：1135

作者：

Wu, Xiaoji ^{[1
,2
,3
,4
,5
]}

Zhang, Yi ^{[1
,2
,3
,4
]}

机构：

[1] Howard Hughes Med Inst, Boston, MA 02115 USA

[2] Boston Childrens Hosp, Program Cellular & Mol Med, WAB-149G,200 Longwood Ave, Boston, MA 02115 USA

[3] Harvard Stem Cell Inst, Boston, MA 02115 USA

[4] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA

[5] Harvard Med Sch, PhD Program Biol & Biomed Sci, Boston, MA 02115 USA

来源：

NATURE REVIEWS GENETICS | 2017年 / 18卷 / 09期

关键词：

EMBRYONIC STEM-CELLS; PRIMORDIAL GERM-CELLS; BASE-RESOLUTION ANALYSIS; ACETYLGLUCOSAMINE TRANSFERASE OGT; 10-11 TRANSLOCATION TET; ACUTE MYELOID-LEUKEMIA; MOUSE PREIMPLANTATION DEVELOPMENT; METHYLCYTOSINE OXIDASES TET1; EXCISION-REPAIR PATHWAY; GENOME-WIDE ANALYSIS;

D O I：

10.1038/nrg.2017.33

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

In mammals, DNA methylation in the form of 5-methylcytosine (5mC) can be actively reversed to unmodified cytosine (C) through TET dioxygenase-mediated oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), followed by replication-dependent dilution or thymine DNA glycosylase (TDG)-dependent base excision repair. In the past few years, biochemical and structural studies have revealed mechanistic insights into how TET and TDG mediate active DNA demethylation. Additionally, many regulatory mechanisms of this process have been identified. Technological advances in mapping and tracing the oxidized forms of 5mC allow further dissection of their functions. Furthermore, the biological functions of active DNA demethylation in various biological contexts have also been revealed. In this Review, we summarize the recent advances and highlight key unanswered questions.

引用

页码：517 / 534

页数：18

共 262 条

[1] Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies [J].

Abdel-Wahab, Omar ;

Mullally, Ann ;

Hedvat, Cyrus ;

Garcia-Manero, Guillermo ;

Patel, Jay ;

Wadleigh, Martha ;

Malinge, Sebastien ;

Yao, JinJuan ;

Kilpivaara, Outi ;

Bhat, Rukhmi ;

Huberman, Kety ;

Thomas, Sabrena ;

Dolgalev, Igor ;

Heguy, Adriana ;

Paietta, Elisabeth ;

Le Beau, Michelle M. ;

Beran, Miloslav ;

Tallman, Martin S. ;

Ebert, Benjamin L. ;

Kantarjian, Hagop M. ;

Stone, Richard M. ;

Gilliland, D. Gary ;

Crispino, John D. ;

Levine, Ross L. .

BLOOD, 2009, 114 (01) :144-147

[2] De novo DNA methylation drives 5hmC accumulation in mouse zygotes [J].

Amouroux, Rachel ;

Nashun, Buhe ;

Shirane, Kenjiro ;

Nakagawa, Shoma ;

Hill, Peter W. S. ;

D'Souza, Zelpha ;

Nakayama, Manabu ;

Matsuda, Masashi ;

Turp, Aleksandra ;

Ndjetehe, Elodie ;

Encheva, Vesela ;

Kudo, Nobuaki R. ;

Koseki, Haruhiko ;

Sasaki, Hiroyiki ;

Hajkova, Petra .

NATURE CELL BIOLOGY, 2016, 18 (02) :225-+

[3] Acute loss of TET function results in aggressive myeloid cancer in mice [J].

An, Jungeun ;

Gonzalez-Avalos, Edahi ;

Chawla, Ashu ;

Jeong, Mira ;

Lopez-Moyado, Isaac F. ;

Li, Wei ;

Goodell, Margaret A. ;

Chavez, Lukas ;

Ko, Myunggon ;

Rao, Anjana .

NATURE COMMUNICATIONS, 2015, 6

[4] Long Noncoding RNA TARID Directs Demethylation and Activation of the Tumor Suppressor TCF21 via GADD45A [J].

Arab, Khelifa ;

Park, Yoon Jung ;

Lindroth, Anders M. ;

Schaefer, Andrea ;

Oakes, Christopher ;

Weichenhan, Dieter ;

Lukanova, Annekatrin ;

Lundin, Eva ;

Risch, Angela ;

Meister, Michael ;

Dienemann, Hendrik ;

Dyckhoff, Gerhard ;

Herold-Mende, Christel ;

Grummt, Ingrid ;

Niehrs, Christof ;

Plass, Christoph .

MOLECULAR CELL, 2014, 55 (04) :604-614

[5] Selective impairment of methylation maintenance is the major cause of DNA methylation reprogramming in the early embryo [J].

Arand, Julia ;

Wossidlo, Mark ;

Lepikhov, Konstantin ;

Peat, Julian R. ;

Reik, Wolf ;

Walter, Joern .

EPIGENETICS & CHROMATIN, 2015, 8

[6] 5-Formylcytosine can be a stable DNA modification in mammals [J].

Bachman, Martin ;

Uribe-Lewis, Santiago ;

Yang, Xiaoping ;

Burgess, Heather E. ;

Iurlaro, Mario ;

Reik, Wolf ;

Murrell, Adele ;

Balasubramanian, Shankar .

NATURE CHEMICAL BIOLOGY, 2015, 11 (08) :555-U40

[7]

Bachman M, 2014, NAT CHEM, V6, P1049, DOI [10.1038/NCHEM.2064, 10.1038/nchem.2064]

[8] Phosphorylation of TET Proteins Is Regulated via O-GlcNAcylation by the O-Linked N-Acetylglucosamine Transferase (OGT) [J].

Bauer, Christina ;

Goebel, Klaus ;

Nagaraj, Nagarjuna ;

Colantuoni, Christian ;

Wang, Mengxi ;

Mueller, Udo ;

Kremmer, Elisabeth ;

Rottach, Andrea ;

Leonhardt, Heinrich .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290 (08) :4801-4812

[9] Specificity of human thymine DNA glycosylase depends on N-glycosidic bond stability [J].

Bennett, Matthew T. ;

Rodgers, M. T. ;

Hebert, Alexander S. ;

Ruslander, Lindsay E. ;

Eisele, Leslie ;

Drohat, Alexander C. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (38) :12510-12519

[10] PGC7 suppresses TET3 for protecting DNA methylation [J].

Bian, Chunjing ;

Yu, Xiaochun .

NUCLEIC ACIDS RESEARCH, 2014, 42 (05) :2893-2905

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