Human Molecular Genetics, 2000, Vol. 9, No. 16 2395-2402
© 2000 Oxford University Press
The DNA methyltransferases of mammals
Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, 701 West 168th Street, New York, NY 10032, USA
The biological significance of 5-methylcytosine was in doubt for many years, but is no longer. Through targeted mutagenesis in mice it has been learnt that every protein shown by biochemical tests to be involved in the establishment, maintenance or interpretation of genomic methylation patterns is encoded by an essential gene. A human genetic disorder (ICF syndrome) has recently been shown to be caused by mutations in the DNA methyltransferase 3B (DNMT3B) gene. A second human disorder (Rett syndrome) has been found to result from mutations in the MECP2 gene, which encodes a protein that binds to methylated DNA. Global genome demethylation caused by targeted mutations in the DNA methyltransferase-1 (Dnmt1) gene has shown that cytosine methylation plays essential roles in X-inactivation, genomic imprinting and genome stabilization. The majority of genomic 5-methylcytosine is now known to enforce the transcriptional silence of the enormous burden of transposons and retroviruses that have accumulated in the mammalian genome. It has also become clear that programmed changes in methylation patterns are less important in the regulation of mammalian development than was previously believed. Although a number of outstanding questions have yet to be answered (one of these questions involves the nature of the cues that designate sites for methylation at particular stages of gametogenesis and early development), studies of DNA methyltransferases are likely to provide further insights into the biological functions of genomic methylation patterns.
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Y.-Z. Ge, M.-T. Pu, H. Gowher, H.-P. Wu, J.-P. Ding, A. Jeltsch, and G.-L. Xu Chromatin Targeting of de Novo DNA Methyltransferases by the PWWP Domain J. Biol. Chem., June 11, 2004; 279(24): 25447 - 25454. [Abstract] [Full Text] [PDF]
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 R Castro, I Rivera, P Ravasco, M E Camilo, C Jakobs, H J Blom, and I T de Almeida 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C->T and 1298A->C mutations are associated with DNA hypomethylation J. Med. Genet., June 1, 2004; 41(6): 454 - 458. [Full Text] [PDF]
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Q. Wu, S. Ohsako, R. Ishimura, J. S. Suzuki, and C. Tohyama Exposure of Mouse Preimplantation Embryos to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Alters the Methylation Status of Imprinted Genes H19 and Igf2 Biol Reprod, June 1, 2004; 70(6): 1790 - 1797. [Abstract] [Full Text] [PDF]
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T. M. Geiman, U. T. Sankpal, A. K. Robertson, Y. Chen, M. Mazumdar, J. T. Heale, J. A. Schmiesing, W. Kim, K. Yokomori, Y. Zhao, et al. Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery Nucleic Acids Res., May 17, 2004; 32(9): 2716 - 2729. [Abstract] [Full Text] [PDF]
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 J. A. Piedrahita, B. Mir, S. Dindot, and S. Walker Somatic Cell Cloning: The Ultimate Form of Nuclear Reprogramming? J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1140 - 1144. [Abstract] [Full Text] [PDF]
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D. Lucifero, M. R.W. Mann, M. S. Bartolomei, and J. M. Trasler Gene-specific timing and epigenetic memory in oocyte imprinting Hum. Mol. Genet., April 15, 2004; 13(8): 839 - 849. [Abstract] [Full Text] [PDF]
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D. C. Malins, K. M. Anderson, N. L. Polissar, G. K. Ostrander, E. T. Knobbe, V. M. Green, N. K. Gilman, and J. L. Spivak Models of granulocyte DNA structure are highly predictive of myelodysplastic syndrome PNAS, April 6, 2004; 101(14): 5008 - 5011. [Abstract] [Full Text] [PDF]
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 V. G. Kossykh and R. S. Lloyd A DNA Adenine Methyltransferase of Escherichia coli That Is Cell Cycle Regulated and Essential for Viability J. Bacteriol., April 1, 2004; 186(7): 2061 - 2067. [Abstract] [Full Text] [PDF]
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 C. E. Blanco-Betancourt, A. Moncla, M. Milili, Y. L. Jiang, E. M. Viegas-Pequignot, B. Roquelaure, I. Thuret, and C. Schiff Defective B-cell-negative selection and terminal differentiation in the ICF syndrome Blood, April 1, 2004; 103(7): 2683 - 2690. [Abstract] [Full Text] [PDF]
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 K. A. Borkovich, L. A. Alex, O. Yarden, M. Freitag, G. E. Turner, N. D. Read, S. Seiler, D. Bell-Pedersen, J. Paietta, N. Plesofsky, et al. Lessons from the Genome Sequence of Neurospora crassa: Tracing the Path from Genomic Blueprint to Multicellular Organism Microbiol. Mol. Biol. Rev., March 1, 2004; 68(1): 1 - 108. [Abstract] [Full Text] [PDF]
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K. Ghoshal, S. Majumder, J. Datta, T. Motiwala, S. Bai, S. M. Sharma, W. Frankel, and S. T. Jacob Role of Human Ribosomal RNA (rRNA) Promoter Methylation and of Methyl-CpG-binding Protein MBD2 in the Suppression of rRNA Gene Expression J. Biol. Chem., February 20, 2004; 279(8): 6783 - 6793. [Abstract] [Full Text] [PDF]
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Y. Ling, U. T. Sankpal, A. K. Robertson, J. G. McNally, T. Karpova, and K. D. Robertson Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription Nucleic Acids Res., January 29, 2004; 32(2): 598 - 610. [Abstract] [Full Text] [PDF]
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C. D. Laird, N. D. Pleasant, A. D. Clark, J. L. Sneeden, K. M. A. Hassan, N. C. Manley, J. C. Vary Jr., T. Morgan, R. S. Hansen, and R. Stoger From The Cover: Hairpin-bisulfite PCR: Assessing epigenetic methylation patterns on complementary strands of individual DNA molecules PNAS, January 6, 2004; 101(1): 204 - 209. [Abstract] [Full Text] [PDF]
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 T.H. BESTOR and D. BOURC'HIS Transposon Silencing and Imprint Establishment in Mammalian Germ Cells Cold Spring Harb Symp Quant Biol, January 1, 2004; 69(0): 381 - 388. [Abstract] [PDF]
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H.T. BJORNSSON, H. CUI, D. GIUS, M.D. FALLIN, and A.P. FEINBERG The New Field Of Epigenomics: Implications for Cancer and Other Common Disease Research Cold Spring Harb Symp Quant Biol, January 1, 2004; 69(0): 447 - 456. [Abstract] [PDF]
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Q. Yan, E. Cho, S. Lockett, and K. Muegge Association of Lsh, a Regulator of DNA Methylation, with Pericentromeric Heterochromatin Is Dependent on Intact Heterochromatin Mol. Cell. Biol., December 1, 2003; 23(23): 8416 - 8428. [Abstract] [Full Text] [PDF]
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 D. Giannino, G. Mele, R. Cozza, L. Bruno, G. Testone, C. Ticconi, G. Frugis, M. B. Bitonti, A. M. Innocenti, and D. Mariotti Isolation and characterization of a maintenance DNA-methyltransferase gene from peach (Prunus persica [L.] Batsch): transcript localization in vegetative and reproductive meristems of triple buds J. Exp. Bot., December 1, 2003; 54(393): 2623 - 2633. [Abstract] [Full Text] [PDF]
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C. D. Carvin, R. D. Parr, and M. P. Kladde Site-selective in vivo targeting of cytosine-5 DNA methylation by zinc-finger proteins Nucleic Acids Res., November 15, 2003; 31(22): 6493 - 6501. [Abstract] [Full Text] [PDF]
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 N. Kunert, J. Marhold, J. Stanke, D. Stach, and F. Lyko A Dnmt2-like protein mediates DNA methylation in Drosophila Development, November 1, 2003; 130(21): 5083 - 5090. [Abstract] [Full Text] [PDF]
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Y.-W. Leu, F. Rahmatpanah, H. Shi, S. H. Wei, J. C. Liu, P. S. Yan, and T. H.-M. Huang Double RNA Interference of DNMT3b and DNMT1 Enhances DNA Demethylation and Gene Reactivation Cancer Res., October 1, 2003; 63(19): 6110 - 6115. [Abstract] [Full Text] [PDF]
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L.-Y. Tang, M. N. Reddy, V. Rasheva, T.-L. Lee, M.-J. Lin, M.-S. Hung, and C.-K. J. Shen The Eukaryotic DNMT2 Genes Encode a New Class of Cytosine-5 DNA Methyltransferases J. Biol. Chem., September 5, 2003; 278(36): 33613 - 33616. [Abstract] [Full Text] [PDF]
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M. F. Paz, S. Wei, J. C. Cigudosa, S. Rodriguez-Perales, M. A. Peinado, T. H.-M. Huang, and M. Esteller Genetic unmasking of epigenetically silenced tumor suppressor genes in colon cancer cells deficient in DNA methyltransferases Hum. Mol. Genet., September 1, 2003; 12(17): 2209 - 2219. [Abstract] [Full Text] [PDF]
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A. Hermann, S. Schmitt, and A. Jeltsch The Human Dnmt2 Has Residual DNA-(Cytosine-C5) Methyltransferase Activity J. Biol. Chem., August 22, 2003; 278(34): 31717 - 31721. [Abstract] [Full Text] [PDF]
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P. T. Georgel, R. A. Horowitz-Scherer, N. Adkins, C. L. Woodcock, P. A. Wade, and J. C. Hansen Chromatin Compaction by Human MeCP2: ASSEMBLY OF NOVEL SECONDARY CHROMATIN STRUCTURES IN THE ABSENCE OF DNA METHYLATION J. Biol. Chem., August 22, 2003; 278(34): 32181 - 32188. [Abstract] [Full Text] [PDF]
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 R. Castro, I. Rivera, E. A. Struys, E. E.W. Jansen, P. Ravasco, M. E. Camilo, H. J. Blom, C. Jakobs, and I. Tavares de Almeida Increased Homocysteine and S-Adenosylhomocysteine Concentrations and DNA Hypomethylation in Vascular Disease Clin. Chem., August 1, 2003; 49(8): 1292 - 1296. [Abstract] [Full Text] [PDF]
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N. Fujita, S. Watanabe, T. Ichimura, S. Tsuruzoe, Y. Shinkai, M. Tachibana, T. Chiba, and M. Nakao Methyl-CpG Binding Domain 1 (MBD1) Interacts with the Suv39h1-HP1 Heterochromatic Complex for DNA Methylation-based Transcriptional Repression J. Biol. Chem., June 20, 2003; 278(26): 24132 - 24138. [Abstract] [Full Text] [PDF]
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F. Fuks, P. J. Hurd, R. Deplus, and T. Kouzarides The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase Nucleic Acids Res., May 1, 2003; 31(9): 2305 - 2312. [Abstract] [Full Text] [PDF]
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