Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.1.1.37 (DNA methyltransferase)
4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The restriction-modification system, named RMMunI, has been purified and characterised from Friend murine erythroleukemia cells. The site-specific endonuclease recognizes and cleaves the 5'C1AATTG nucleotide sequence. RMunI is an isoschizomer of RMfeI from Mycoplasma fermentans. Site-specific methylase modifies the second adenine residue in the same sequence (5'Cam6ATTG). It was established that the discovered enzymatic system is from mycoplasma which contaminates cell lines. Mycoplasma's DNA hybridizes with species-specific DNA probed for Mycoplasma fermentans and Mycoplasma arginini. The possible role of mycoplasmic restriction-modification enzymes in the process of acquired immune deficiency syndrome are discussed.
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PMID:[Mycoplasma restriction-modification system MunI and its possible role in pathogenesis processes]. 140 10

The human melanoma cell line M21 can be induced to differentiate into oligodendrocyte-like cells with concommitant cessation of cell division. Cytosine-arabinoside, 5-aza-2'-deoxycytidine, hydroxyurea, aphidicolin, and phorbol-12-myristate-13-acetate were found to be potent differentiation inducers. We have analyzed the changes of methylation of DNA cytosines that occur after treatment of M21 cells with these compounds. Although DNA methylation levels remain unchanged in the presence of aphidicolin and phorbol ester, 5-aza-2'-deoxycytidine-induced differentiation of these cells results in a 40% DNA demethylation. On the other hand, hydroxyurea and cytosine-arabinoside treatment causes DNA hypermethylation, which, in the case of the cytidine analogue is of only transient nature. These results show that the differentiation of human melanoma cells can be accompanied by variable changes of DNA methylation levels. In another set of experiments, the DNA methylation levels have been analyzed during cytosine-arabinoside-induced differentiation of human K562 erythroleukemia cells. In this system, a transient DNA demethylation precedes the establishment of the differentiated phenotype. Since DNA replication is inhibited, this demethylation cannot be explained by inhibition of the maintenance activity of DNA methyltransferase, but is more likely caused by an active excision of 5-methylcytosine from DNA.
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PMID:The DNA methylation system in proliferating and differentiated cells. 247 29

Actinomycin D caused the production of hypomethylated DNA in cultured Friend erythroleukemia cells at cell culture concentrations of 1-4 ng per ml. Inhibition of DNA methyltransferase in cell-free assays was kinetically complex, with mixed-type inhibition. Cornish-Bowden graphical analysis was used to derive a Ki of about 35 nmol Act D per mg DNA. Although nuclei from drug-treated cells were found to contain hypomethylated DNA and DNA methyltransferase could be extracted from the nuclei, the methyl-accepting ability of DNA in whole nuclei themselves was not elevated. We conclude that the low level of Act D bound to DNA in the nuclei is sufficient to prevent the remethylation of hypomethylated sites.
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PMID:Inhibition of DNA methylation in Friend erythroleukemia cells by actinomycin D. 261 50

The enzymatic methylation of the 5'-flanking region of the mouse beta-globin (major) gene containing putative regulatory regions has been investigated. In vitro methylation of this 368-base pair regulatory DNA by a DNA methyltransferase obtained from mouse erythroleukemia cells yields an asymmetric methylation pattern. Of the 10 available CG pairs, only 5-6 are modified, leading to one hemimethylated site and two apparently fully methylated sites. Only CG pairs which are localized in a 29-base pair cluster are methylated. The data suggest that a CG cluster approximately 100 base pairs upstream from the CAP site may be the in vivo site of methylation in the 5'-regulator region of the mouse beta-globin gene.
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PMID:In vitro methylation of the 5'-flanking regions of the mouse beta-globin gene. 303 5

A naturally occurring methylation inhibitor isolated from rabbit liver and named methinin inhibits a number of methyltransferases. Methinin is a low-molecular-weight compound (1,400) that has an active amine group. This compound inhibits the DNA methyltransferase of human erythroleukemia cells (K562) in vitro. When the K562 cells were grown in medium containing methinin, fetal hemoglobin was produced. Small but detectable amounts of adult hemoglobin were also produced. Methinin was not toxic to these cells. The overall rate of genomic DNA methylation was reduced by 60% in cells grown in medium containing methinin. Southern blots of genomic DNA from methinin-treated cells and untreated cells hybridized to a 32P-labeled globin gene probe showed that one site in the globin gene region was hypomethylated. Methinin is a naturally occurring compound which inhibits DNA methylation both in vitro and in vivo.
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PMID:Naturally occurring methylation inhibitor: DNA hypomethylation and hemoglobin synthesis in human K562 cells. 347 16

Friend murine erythroleukemia cells were found to contain three distinct species of DNA (cytosine-5-)-methyltransferase (DNA MeTase) whose relative proportions were a characteristic function of the proliferative state of the cells. Rapidly proliferating cells contained a Mr 190,000 species of DNA MeTase (DNA MeTase III), whereas cells in the late logarithmic/early plateau phase of cellular growth contained two species of Mr 150,000 and 175,000 (DNA MeTase I and II); stationary phase cells contained primarily DNA MeTase I. The three species of DNA MeTase displayed structural similarities, as determined by analysis of partial proteolysis products, and have similar de novo sequence specificities in transmethylation reactions involving purified enzyme and prokaryotic DNA. The different relative proportions of the enzymes in cells under different growth conditions suggest that the three species of DNA MeTase fulfill different roles in processes leading to the perpetuation of DNA methylation patterns.
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PMID:Growth-dependent expression of multiple species of DNA methyltransferase in murine erythroleukemia cells. 385 9

Methyl-accepting assays and a sensitive method for labeling specific CpG sites have been used to show that the DNA of F9 embryonal carcinoma cells decreases in 5-methylcytosine content by ca. 9% during retinoic acid-induced differentiation, whereas the DNA of dimethyl sulfoxide-induced Friend murine erythroleukemia (MEL) cells loses ca. 3.8% of its methyl groups. These values correspond to the demethylation of 2.2 X 10(6) and 0.9 X 10(6) 5'-CpG-3' sites per haploid genome in differentiating F9 and MEL cells, respectively. Fluorography of DNA restriction fragments methylated in vitro and displayed on agarose gels showed that demethylation occurred throughout the genome. In uninduced F9 cells, the sequence TCGA tended to be more heavily methylated than did the sequence CCGG, whereas this tendency was reversed in MEL cells. The kinetics of in vitro DNA methylation reactions catalyzed by MEL cell DNA methyltransferase showed that substantial numbers of hemimethylated sites accumulate in the DNA of terminally differentiating F9 and MEL cells, implying that a partial loss of DNA-methylating activity may accompany terminal differentiation in these two cell types.
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PMID:Differentiation of two mouse cell lines is associated with hypomethylation of their genomes. 609 40

Treatment of Friend erythroleukemia cells with the antileukemic drugs 5-azacytidine and 5-aza-2'-deoxycytidine leads to rapid, time-dependent, and dose-dependent decrease of DNA methyltransferase activity and synthesis of markedly undermethylated DNA. Since this DNA is at least partially methylated in vivo and serves as an excellent substrate for methylation in vitro, hypomethylation of DNA in analog-treated cells appears to result from the loss of DNA methyltransferase, rather than from an inherent inability of 5-azacytosine- substituted DNA to serve as a methyl acceptor. Inhibition of DNA synthesis blocks the loss of DNA methyltransferase activity while inhibitors of RNA synthesis do not, suggesting that the analogs must be incorporated into DNA to mediate their effect on the enzyme, and that minor substitution of 5-azacytosine for cytosine in DNA (approximately 0.3%) suffices to inactivate more than 95% of the enzyme in the cell. Several lines of evidence link changes in the pattern of DNA modification with differentiation. In this regard, it is significant that 5-azacytidine and 5-aza-2'-deoxycytidine act as weak inducers of erythroid differentiation of Friend erythroleukemia cells in the same concentration range where they affect DNA methyltransferase activity. For differentiation to proceed, the cells must be washed free of the drugs. Less than 24 h later, normal levels of DNA methyltransferase activity are restored and within 48 h, DNA isolated from the cells is not detectably undermethylated. This may in part explain why 5-azacytidine and 5-aza-2'-deoxycytidine induce differentiation in less than 15% of the population despite their initial profound effect on DNA methylation.
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PMID:Inhibition of DNA methyltransferase and induction of Friend erythroleukemia cell differentiation by 5-azacytidine and 5-aza-2'-deoxycytidine. 617 84

Chromatin fragments released from intact Friend erythroleukemia cell nuclei during limited incubation with micrococcal nuclease, DNase II or DNase I were analyzed to determine the distribution of DNA methyltransferase in chromatin. The enzyme was released in a free form when internucleosomal DNA was digested with micrococcal nuclease but was found associated with Mg++-precipitable polynucleosomes after DNase II digestion. Less than 25% of the enzyme was released from nuclei incubated with DNase I under conditions where transcriptionally active chromatin should have been completely digested. These results indicated that the bulk of DNA methyltransferase was bound to "linker" DNA in condensed regions of chromatin. Preferential rebinding of free enzyme to linker DNA was also demonstrated in vitro. The possibility that chromatin proteins play a role in regulating access of DNA methyltransferase to specific sites in DNA is discussed in light of these findings.
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PMID:Localization of DNA methyltransferase in the chromatin of Friend erythroleukemia cells. 627 20

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 phi X174 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 methyl-accepting 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.
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PMID:Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA. 657 43


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