Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Causes underlying inter-individual variations in DNA methylation profiles among normal healthy populations are not thoroughly understood. To investigate the contribution of genetic variation in DNA methyltransferase (DNMT) genes to such epigenetic variation, we performed a systematic search for polymorphisms in all known human DNMT genes [DNMT1, DNMT3A, DNMT3B, DNMT3L and DNMT2 (TRDMT1)] in 192 healthy males and females. One hundred and eleven different polymorphisms were detected. Of these, 24 were located in coding regions and 10 resulted in an amino acid change that may affect the corresponding DNMT protein structure or function. Association analysis between all major polymorphisms (frequency > 1%) and quantitative DNA methylation profiles did not return significant results after correction for multiple testing. Polymorphisms leading to an amino acid change were further investigated for changes in global DNA methylation by differential methylation hybridization. This analysis revealed that a rare change at DNMT3L (R271Q) was associated with significant DNA hypomethylation. Biochemical characterization confirmed that DNMT3L(R271Q) is impaired in its ability to stimulate de novo DNA methylation by DNMT3A. Methylated DNA immunoprecipitation based analysis using CpG island microarrays revealed that the hypomethylation in this sample preferentially clustered to subtelomeric genomic regions with affected loci corresponding to a subset of repetitive CpG islands with low predicted promoter potential located outside of genes.
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PMID:A systematic search for DNA methyltransferase polymorphisms reveals a rare DNMT3L variant associated with subtelomeric hypomethylation. 1924 18

Cancer is the second leading cause of death in US. Despite the emergence of new, targeted agents, and the use of various therapeutic combinations, none of the available treatment options are curative in patients with advanced cancer. Epigenetic alterations are increasingly recognized as valuable targets for the development of cancer therapies. DNA methylation at the 5-position of cytosine, catalyzed by DNA methyltransferases (DNMTs), is the predominant epigenetic modification in mammals. DNMT1, the major enzyme responsible for maintenance of the DNA methylation pattern is located at the replication fork and methylates newly biosynthesized DNA. DNMT2 or TRDMT1, the smallest mammalian DNMT is believed to participate in the recognition of DNA damage, DNA recombination, and mutation repair. It is composed solely of the C-terminal domain, and does not possess the regulatory N-terminal region. The levels of DNMTs, especially those of DNMT3B, DNMT3A, and DNMT3L, are often increased in various cancer tissues and cell lines, which may partially account for the hypermethylation of promoter CpG-rich regions of tumor suppressor genes in a variety of malignancies. Moreover, it has been shown to function in self-renewal and maintenance of colon cancer stem cells and need to be studied in several cancers. Inhibition of DNMTs has demonstrated reduction in tumor formation in part through the increased expression of tumor suppressor genes. Hence, DNMTs can potentially be used as anti-cancer targets. Dietary phytochemicals also inhibit DNMTs and cancer stem cells; this represents a promising approach for the prevention and treatment of many cancers.
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PMID:DNA methyltransferases: a novel target for prevention and therapy. 2482 69

In eukaryotes, cytosine methylation regulates diverse biological processes such as gene expression, development and maintenance of genomic integrity. However, cytosine methylation and its functions in pathogenic apicomplexan protozoans remain enigmatic. To address this, here we investigated the presence of cytosine methylation in the nucleic acids of the protozoan Plasmodium falciparum. Interestingly, P. falciparum has TRDMT1, a conserved homologue of DNA methyltransferase DNMT2. However, we found that TRDMT1 did not methylate DNA, in vitro. We demonstrate that TRDMT1 methylates cytosine in the endogenous aspartic acid tRNA of P. falciparum. Through RNA bisulfite sequencing, we mapped the position of 5-methyl cytosine in aspartic acid tRNA and found methylation only at C38 position. P. falciparum proteome has significantly higher aspartic acid content and a higher proportion of proteins with poly aspartic acid repeats than other apicomplexan pathogenic protozoans. Proteins with such repeats are functionally important, with significant roles in host-pathogen interactions. Therefore, TRDMT1 mediated C38 methylation of aspartic acid tRNA might play a critical role by translational regulation of important proteins and modulate the pathogenicity of the malarial parasite.
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PMID:DNA methyltransferase homologue TRDMT1 in Plasmodium falciparum specifically methylates endogenous aspartic acid tRNA. 2884 33

Eukaryotic 5-methylcytosine RNA methyltransferases catalyze the transfer of a methyl group to the fifth carbon of a cytosine base in RNA sequences to produce 5-methylcytosine (m5C). m5C RNA methyltransferases play a crucial role in the maintenance of functionality and stability of RNA. Viruses have developed a number of strategies to suppress host innate immunity and ensure efficient transcription and translation for the replication of new virions. One such viral strategy is to use host m5C RNA methyltransferases to modify viral RNA and thus to affect antiviral host responses. Here, we summarize the latest findings concerning the roles of m5C RNA methyltransferases, namely, NOL1/NOP2/SUN domain (NSUN) proteins and DNA methyltransferase 2/tRNA methyltransferase 1 (DNMT2/TRDMT1) during viral infections. Moreover, the use of m5C RNA methyltransferase inhibitors as an antiviral therapy is discussed.
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PMID:The Roles of Host 5-Methylcytosine RNA Methyltransferases during Viral Infections. 3314 33