Dnmt2-dependent methylomes lack defined DNA methylation patterns

被引：177

作者：

Raddatz, Guenter ^{[1
]}

Guzzardo, Paloma M. ^{[3
]}

Olova, Nelly ^{[4
]}

Fantappie, Marcelo Rosado ^{[5
]}

Rampp, Markus ^{[6
]}

Schaefer, Matthias ^{[1
]}

Reik, Wolf ^{[4
,7
,8
]}

Hannon, Gregory J. ^{[2
,3
]}

Lyko, Frank ^{[1
]}

机构：

[1] German Canc Res Ctr, Div Epigenet, DKFZ ZMBH Alliance, D-69120 Heidelberg, Germany

[2] Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA

[3] Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA

[4] Babraham Inst, Epigenet Programme, Cambridge CB22 3AT, England

[5] Univ Fed Rio de Janeiro, Inst Bioquim Med, Programa Biol Mol & Biotecnol, Ctr Ciencias Saude, BR-21941590 Rio De Janeiro, Brazil

[6] Max Planck Inst Plasma Phys, Max Planck Soc, Comp Ctr RZG, D-85748 Garching, Germany

[7] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England

[8] Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 21期

基金：

美国国家卫生研究院; 英国生物技术与生命科学研究理事会; 英国医学研究理事会; 英国惠康基金;

关键词：

RNA methylation; epigenetics; EMBRYONIC STEM-CELLS; HUMAN DNMT2; METHYLTRANSFERASE HOMOLOG; CYTOSINE METHYLATION; RNA METHYLATION; MAINTENANCE; EVOLUTION; TRNA(ASP); BINDING; PLANTS;

D O I：

10.1073/pnas.1306723110

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Several organisms have retained methyltransferase 2(Dnmt2) as their only candidate DNA methyltransferase gene. However, information about Dnmt2-dependent methylation patterns has been limited to a few isolated loci and the results have been discussed controversially. In addition, recent studies have shown that Dnmt2 functions as a tRNA methyltransferase, which raised the possibility that Dnmt2-only genomes might be unmethylated. We have now used whole-genome bisulfite sequencing to analyze the methylomes of Dnmt2-only organisms at single-base resolution. Our results show that the genomes of Schistosoma mansoni and Drosophila melanogaster lack detectable DNA methylation patterns. Residual unconverted cytosine residues shared many attributes with bisulfite deamination artifacts and were observed at comparable levels in Dnmt2-deficient flies. Furthermore, genetically modified Dnmt2-only mouse embryonic stem cells lost the DNA methylation patterns found in wild-type cells. Our results thus uncover fundamental differences among animal methylomes and suggest that DNA methylation is dispensable for a considerable number of eukaryotic organisms.

引用

页码：8627 / 8631

页数：5

共 42 条

[1] Pmt1, a Dnmt2 homolog in Schizosaccharomyces pombe, mediates tRNA methylation in response to nutrient signaling [J].

Becker, Maria ;

Mueller, Sara ;

Nellen, Wolfgang ;

Jurkowski, Tomasz P. ;

Jeltsch, Albert ;

Ehrenhofer-Murray, Ann E. .

NUCLEIC ACIDS RESEARCH, 2012, 40 (22) :11648-11658

[2] Structure of human DNMT2, an enigmatic DNA methyltransferase homolog that displays denaturant-resistant binding to DNA [J].

Dong, AP ;

Yoder, JA ;

Zhang, X ;

Zhou, L ;

Bestor, TH ;

Cheng, XD .

NUCLEIC ACIDS RESEARCH, 2001, 29 (02) :439-448

[3] Efficient RNA virus control in Drosophila requires the RNA methyltransferase Dnmt2 [J].

Durdevic, Zeljko ;

Hanna, Katharina ;

Gold, Beth ;

Pollex, Tim ;

Cherry, Sara ;

Lyko, Frank ;

Schaefer, Matthias .

EMBO REPORTS, 2013, 14 (03) :269-275

[4] Phenotypic plasticity and the epigenetics of human disease [J].

Feinberg, Andrew P. .

NATURE, 2007, 447 (7143) :433-440

[5] Conservation and divergence of methylation patterning in plants and animals [J].

Feng, Suhua ;

Cokus, Shawn J. ;

Zhang, Xiaoyu ;

Chen, Pao-Yang ;

Bostick, Magnolia ;

Goll, Mary G. ;

Hetzel, Jonathan ;

Jain, Jayati ;

Strauss, Steven H. ;

Halpern, Marnie E. ;

Ukomadu, Chinweike ;

Sadler, Kirsten C. ;

Pradhan, Sriharsa ;

Pellegrini, Matteo ;

Jacobsen, Steven E. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (19) :8689-8694

[6] Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation [J].

Ficz, Gabriella ;

Branco, Miguel R. ;

Seisenberger, Stefanie ;

Santos, Fatima ;

Krueger, Felix ;

Hore, Timothy A. ;

Marques, C. Joana ;

Andrews, Simon ;

Reik, Wolf .

NATURE, 2011, 473 (7347) :398-U589

[7] Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni [J].

Geyer, Kathrin K. ;

Lopez, Carlos M. Rodriguez ;

Chalmers, Iain W. ;

Munshi, Sabrina E. ;

Truscott, Martha ;

Heald, James ;

Wilkinson, Mike J. ;

Hoffmann, Karl F. .

NATURE COMMUNICATIONS, 2011, 2

[8] Eukaryotic cytosine methyltransferases [J].

Goll, MG ;

Bestor, TH .

ANNUAL REVIEW OF BIOCHEMISTRY, 2005, 74 :481-514

[9] Methylation of tRNAAsP by the DNA methyltransferase homolog Dnmt2 [J].

Goll, MG ;

Kirpekar, F ;

Maggert, KA ;

Yoder, JA ;

Hsieh, CL ;

Zhang, XY ;

Golic, KG ;

Jacobsen, SE ;

Bestor, TH .

SCIENCE, 2006, 311 (5759) :395-398

[10] DNA of Drosophila melanogaster contains 5-methylcytosine [J].

Gowher, H ;

Leismann, O ;

Jeltsch, A .

EMBO JOURNAL, 2000, 19 (24) :6918-6923

← 1 2 3 4 5 →