S-adenosylmethionine: DNA-cytosine 5-methyltransferase from a Novikoff rat hepatoma cell line

Sneider, Thomas W.; Teague, W. Martin; Rogachevsky, L.M.

doi:10.1093/nar/2.10.1685

Cited by 70 publications

(13 citation statements)

References 18 publications

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“…luteus DNA (33 molt C) which was rendered hemimethylated by extensive nick translation in the presence of m5dCTP, dGTP, dATP, and dTTP and phage XP12 DNA (34 molt m5C; 23,24) which was hemimethylated by similar nicktranslation using dCTP instead of m5dCTP served as excellent substrates for human placental DNA methyltransferase ( Table 2). Similar results had been found for bovine, rodent, and human DNA methyltransferases when normal mammalian DNA was compared to DNA made hemimethylated by growth of cultured cells in the presence of antimetabolites or by forming a heteroduplex of the sequence cloned in E. coli with the genomic mammalian sequence (9,11,12,33,43). These findings are consistent with the hypothesis that the mammalian DNA methyltransferases thus far isolated function mostly in maintenance-type DNA methylation, that is, in methylation of 5'-m5C-G-3'/3'-G-C-5' sites created by replication of bifilarly methylated C-G sites (1).…”

Section: Discussionsupporting

confidence: 73%

“…DNA regions methylated in a C-G dinucleotide sequence on only one strand (hemimethylated) can be methylated in the complementary C-G sequence by a maintenance methylation reaction in vivo much more readily than can a symmetrically unmethylated C-C sequence (1,7,8) in a de novo methylation reaction. A preference for methylation of hemimethyvated C-G sequences has been observed with mammalian DNA methylases in vitro (7,(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

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Human placental DNA methyltransferase: DNA substrate and DNA binding specificity

1984

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We have partially purified a DNA methyltransferase from human placenta using a novel substrate for a highly sensitive assay of methylation of hemimethylated DNA. This substrate was prepared by extensive nick translation of bacteriophage XP12 DNA, which normally5 has virtually all of its cytosine residues replaced by 5-methylcytosine (m C). Micrococcus luteus DNA wgs just as good a substrate if it was first similarly nick translated with m dCTP instead of dCTP in the polymerization mixture. At different stages in purification and under various conditions (including in the _presence or absence of high mobility group proteins), the methylation of m C-deficient DVA and that of hemimethylated DNA were compared. Although hemimethylated, m C-rich DNAs were much better substrates than were m C-deficient DNAs and normal XP12 DNA could not be methylated, all of these DNAs were bound equally well by the enzyme. In contrast, from the same placental extraSt, a DNAbinding protein of unknown functon was isolated which binds to m C-rich DNA in preference to the analogous m C-poor DNA.

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Human placental DNA methyltransferase: DNA substrate and DNA binding specificity

1984

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“…DNA MeTases prepared from a number of rodent (14)(15)(16)(17) and human (18) sources have been shown to require CpG-containing DNA, although additional sequence requirements have not been identified. A crude preparation of DNA MeTase from mouse ascites cells showed a strong preference for hemimethylated sites (19), and a "processive" mode of action has been postulated on the basis of the sensitivity of the methylation reaction to increasing ionic strength (14) and to 5-azacytosine-substituted DNA (20).…”

mentioning

confidence: 99%

Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA.

Bestor¹,

Ingram²

1983

Proc. Natl. Acad. Sci. U.S.A.

326

162

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Dye-ligand chromatography on Cibacron blue F3GA-agarose has been used to resolve two species of DNA (cytosine-5-)-methyltransferase from nuclear extracts of uninduced Friend murine erythroleukemia cells. Each species has been highly purified; the activities in the first and second peaks were associated with polypeptides of Mr 150,000 and 175,000, respectively.Analysis of substrate specificity with synthetic DNAs and restriction fragments of 4X174 replicative form DNA and pBR322 DNA showed that neither enzyme had dependence on the sequence context of CpG dinucleotides; poly(dG-dC) had the greatest methylaccepting activity of any unmethylated DNA substrate tested. De novo methylation by both enzymes was inefficient relative to methylation of hemimethylated sites. Methyl-accepting activity was strongly dependent on DNA chain length. This observation suggests that binding to DNA, followed by one-dimensional diffusion of enzyme along the DNA molecule, is important in the mechanism by which DNA methyltransferase locates its recognition sites.DNA methylation in cells from vertebrates is a post-replication process involving the transfer of methyl groups from S-adenosyl L-methionine (AdoMet) to the 5 position of cytosine residues through the action of DNA methyltransferase [DNA MeTase; DNA (cytosine-5-)-methyltransferase, EC 2.1.1.37]. Methylated cytosine residues are located primarily within the dinucleotide 5' CpG 3' (1) and are found in tissue-specific amounts and positions (2). Sano and Sager (3) reported that, in bovine satellite I DNA, 5-methylcytosine (m5C) residues are located exclusively 5' to G residues, occur in clusters, and tend to be located within short self-complementary sequences; the distribution of m5C residues within this DNA showed striking tissue-specific variation.Changes in amounts and locations of m5C residues in DNA appear to be a part of the developmental program in higher cells (reviewed in ref. 4), and it has been demonstrated for many different genes that the loss of methyl groups from specific sites is correlated with the transcriptional activation of adjacent sequences (5-9). Also, in vitro enzymatic methylation of CpG dinucleotides by the bacterial restriction methyltransferase MHpa II inhibits expression of viral (10) and cellular (11) genes after introduction of the methylated DNA into cells. The pattern of methylation is maintained during subsequent cell divisions (12). Treatment of cultured cells with inhibitors of DNA methylation leads to the induction of certain genes with a concomitant reduction in the number of associated methylated CpG sites (13).Despite the apparent biological importance of DNA methylation it is not at all clear how patterns of methylation are established and maintained within the genome. DNA MeTases prepared from a number of rodent (14-17) and human (18) sources have been shown to require CpG-containing DNA, although additional sequence requirements have not been identified. A crude preparation of DNA MeTase from mouse ascites cells showed a strong pre...

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“…For example, the one-carbon metabolic pathway is utilized to generate Sadenosylmethionine, the methyl donor necessary for DNA methyltransferase activity. Choline, methionine, folate, vitamin B 12 , vitamin B 6 , and riboflavin are strategic dietary factors involved in the efficient maintenance of methyl donor pools and healthy DNA methylation status [99]. Deficiencies of diet-provided substrates and cofactors in one-carbon metabolism may therefore result in impaired DNA methylation which is linked to increased risks for neural tube defects, cardiovascular diseases and cancers [100].…”

Section: Epigenetic Alterations and Environmental Exposurementioning

confidence: 99%

Toxicogenomics and Cancer Susceptibility: Advances with Next-Generation Sequencing

Mei

Hong

et al. 2014

Journal of Environmental Science and Health, Part C

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The aim of this review is to comprehensively summarize the recent achievements in the field of toxicogenomics and cancer research regarding genetic-environmental interactions in carcinogenesis and detection of genetic aberrations in cancer genomes by next-generation sequencing technology. Cancer is primarily a genetic disease in which genetic factors and environmental stimuli interact to cause genetic and epigenetic aberrations in human cells. Mutations in the germline act as either high-penetrance alleles that strongly increase the risk of cancer development, or as low-penetrance alleles that mildly change an individual's susceptibility to cancer. Somatic mutations, resulting from either DNA damage induced by exposure to environmental mutagens or from spontaneous errors in DNA replication or repair are involved in the development or progression of the cancer. Induced or spontaneous changes in the epigenome may also drive carcinogenesis. Advances in next-generation sequencing technology provide us opportunities to accurately, economically, and rapidly identify genetic variants, somatic mutations, gene expression profiles, and epigenetic alterations with single-base resolution. Whole genome sequencing, whole exome sequencing, and RNA sequencing of paired cancer and adjacent normal tissue present a comprehensive picture of the cancer genome. These new findings should benefit public health by providing insights in understanding cancer biology, and in improving cancer diagnosis and therapy.

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S-adenosylmethionine: DNA-cytosine 5-methyltransferase from a Novikoff rat hepatoma cell line

Cited by 70 publications

References 18 publications

Human placental DNA methyltransferase: DNA substrate and DNA binding specificity

Human placental DNA methyltransferase: DNA substrate and DNA binding specificity

Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA.

Toxicogenomics and Cancer Susceptibility: Advances with Next-Generation Sequencing

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