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Letteratura scientifica selezionata sul tema "DNMT2"

Autore: Grafiati

Pubblicato: 10 dicembre 2022

Ultima modifica: 9 marzo 2023

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Articoli di riviste sul tema "DNMT2"

1

MUND, Cora, Tanja MUSCH, Martin STRÖDICKE, Birte ASSMANN, En LI e Frank LYKO. "Comparative analysis of DNA methylation patterns in transgenic Drosophila overexpressing mouse DNA methyltransferases". Biochemical Journal 378, n. 3 (15 marzo 2004): 763–68. http://dx.doi.org/10.1042/bj20031567.

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DNA methyltransferases (Dnmts) mediate the epigenetic modification of eukaryotic genomes. Mammalian DNA methylation patterns are established and maintained by co-operative interactions among the Dnmt proteins Dnmt1, Dnmt3a and Dnmt3b. Owing to their simultaneous presence in mammalian cells, the activities of individual Dnmt have not yet been determined. This includes a fourth putative Dnmt, namely Dnmt2, which has failed to reveal any activity in previous assays. We have now established transgenic Drosophila strains that allow for individual overexpression of all known mouse Dnmts. Quantitative analysis of genomic cytosine methylation levels demonstrated a robust Dnmt activity for the de novo methyltransferases Dnmt3a and Dnmt3b. In addition, we also detected a weak but significant activity for Dnmt2. Subsequent methylation tract analysis by genomic bisulphite sequencing revealed that Dnmt3 enzymes preferentially methylated CpG dinucleotides in a processive manner, whereas Dnmt2 methylated isolated cytosine residues in a non-CpG dinucleotide context. Our results allow a direct comparison of the activities of mammalian Dnmts and suggest a significant functional specialization of these enzymes.

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2

Liu, Kui, Yun Fei Wang, Carmen Cantemir e Mark T. Muller. "Endogenous Assays of DNA Methyltransferases: Evidence for Differential Activities of DNMT1, DNMT2, and DNMT3 in Mammalian Cells In Vivo". Molecular and Cellular Biology 23, n. 8 (15 aprile 2003): 2709–19. http://dx.doi.org/10.1128/mcb.23.8.2709-2719.2003.

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ABSTRACT While CpG methylation can be readily analyzed at the DNA sequence level in wild-type and mutant cells, the actual DNA (cytosine-5) methyltransferases (DNMTs) responsible for in vivo methylation on genomic DNA are less tractable. We used an antibody-based method to identify specific endogenous DNMTs (DNMT1, DNMT1b, DNMT2, DNMT3a, and DNMT3b) that stably and selectively bind to genomic DNA containing 5-aza-2′-deoxycytidine (aza-dC) in vivo. Selective binding to aza-dC-containing DNA suggests that the engaged DNMT is catalytically active in the cell. DNMT1b is a splice variant of the predominant maintenance activity DNMT1, while DNMT2 is a well-conserved protein with homologs in plants, yeast, Drosophila, humans, and mice. Despite the presence of motifs essential for transmethylation activity, catalytic activity of DNMT2 has never been reported. The data here suggest that DNMT2 is active in vivo when the endogenous genome is the target, both in human and mouse cell lines. We quantified relative global genomic activity of DNMT1, -2, -3a, and -3b in a mouse teratocarcinoma cell line. DNMT1 and -3b displayed the greatest in vivo binding avidity for aza-dC-containing genomic DNA in these cells. This study demonstrates that individual DNMTs can be tracked and that their binding to genomic DNA can be quantified in mammalian cells in vivo. The different DNMTs display a wide spectrum of genomic DNA-directed activity. The use of an antibody-based tracking method will allow specific DNMTs and their DNA targets to be recovered and analyzed in a physiological setting in chromatin.

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Del Castillo Falconi, Victor M., Karla Torres-Arciga, Genaro Matus-Ortega, José Díaz-Chávez e Luis A. Herrera. "DNA Methyltransferases: From Evolution to Clinical Applications". International Journal of Molecular Sciences 23, n. 16 (12 agosto 2022): 8994. http://dx.doi.org/10.3390/ijms23168994.

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DNA methylation is an epigenetic mark that living beings have used in different environments. The MTases family catalyzes DNA methylation. This process is conserved from archaea to eukaryotes, from fertilization to every stage of development, and from the early stages of cancer to metastasis. The family of DNMTs has been classified into DNMT1, DNMT2, and DNMT3. Each DNMT has been duplicated or deleted, having consequences on DNMT structure and cellular function, resulting in a conserved evolutionary reaction of DNA methylation. DNMTs are conserved in the five kingdoms of life: bacteria, protists, fungi, plants, and animals. The importance of DNMTs in whether methylate or not has a historical adaptation that in mammals has been discovered in complex regulatory mechanisms to develop another padlock to genomic insurance stability. The regulatory mechanisms that control DNMTs expression are involved in a diversity of cell phenotypes and are associated with pathologies transcription deregulation. This work focused on DNA methyltransferases, their biology, functions, and new inhibitory mechanisms reported. We also discuss different approaches to inhibit DNMTs, the use of non-coding RNAs and nucleoside chemical compounds in recent studies, and their importance in biological, clinical, and industry research.

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KIM, SEON-HEE, HYE-JEONG CHO, WOON-MOK SOHN, CHUN-SEOB AHN, YOON KONG, HYUN-JONG YANG e YOUNG-AN BAE. "Egg-specific expression of protein with DNA methyltransferase activity in the biocarcinogenic liver fluke Clonorchis sinensis". Parasitology 142, n. 9 (3 giugno 2015): 1228–38. http://dx.doi.org/10.1017/s0031182015000566.

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SUMMARYDespite recent reports regarding the biology of cytosine methylation in Schistosoma mansoni, the impact of the regulatory machinery remains unclear in diverse platyhelminthes. This ambiguity is reinforced by discoveries of DNA methyltransferase 2 (DNMT2)-only organisms and the substrate specificity of DNMT2 preferential to RNA molecules. Here, we characterized a novel DNA methyltransferase, named CsDNMT2, in a liver fluke Clonorchis sinensis. The protein exhibited structural properties conserved in other members of the DNMT2 family. The native and recombinant CsDNMT2 exhibited considerable enzymatic activity on DNA. The spatiotemporal expression of CsDNMT2 mirrored that of 5-methylcytosine (5 mC), both of which were elevated in the C. sinensis eggs. However, CsDNMT2 and 5 mC were marginally detected in other histological regions of C. sinensis adults including ovaries and seminal receptacle. The methylation site seemed not related to genomic loci occupied by progenies of an active long-terminal-repeat retrotransposon. Taken together, our data strongly suggest that C. sinensis has preserved the functional DNA methylation machinery and that DNMT2 acts as a genuine alternative to DNMT1/DNMT3 to methylate DNA in the DNMT2-only organism. The epigenetic regulation would target functional genes primarily involved in the formation and/or maturation of eggs, rather than retrotransposons.

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5

Zhu, Huolan, Xiang Wang, Xuyang Meng, Yiya Kong, Yi Li, Chenguang Yang, Ying Guo et al. "Selenium Supplementation Improved Cardiac Functions by Suppressing DNMT2-Mediated GPX1 Promoter DNA Methylation in AGE-Induced Heart Failure". Oxidative Medicine and Cellular Longevity 2022 (6 aprile 2022): 1–12. http://dx.doi.org/10.1155/2022/5402997.

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Objective. Advanced glycation end products (AGEs) are featured metabolites associated with diabetic cardiomyopathy which is characterized by heart failure caused by myocyte apoptosis. Selenium was proved cardioprotective. This study was aimed at investigating the therapeutic effects and underlying mechanisms of selenium supplementation on AGE-induced heart failure. Methods. Rats and primary myocytes were exposed to AGEs. Selenium supplementation was administrated. Cardiac functions and myocyte apoptosis were evaluated. Oxidative stress was assessed by total antioxidant capacity (TAC), reactive oxygen species (ROS) generation, and GPX activity. Expression levels of DNA methyltransferases (DNMTs) and glutathione peroxidase 1 (GPX1) were evaluated. DNA methylation of the GPX1 promoter was analyzed. Results. AGE exposure elevated intracellular ROS generation, induced myocyte apoptosis, and impaired cardiac functions. AGE exposure increased DNMT1 and DNMT2 expression, leading to the reduction of GPX1 expression and activity in the heart. Selenium supplementation decreased DNMT2 expression, recovered GPX1 expression and activity, and alleviated intracellular ROS generation and myocyte apoptosis, resulting in cardiac function recovery. DNA methylation analysis in primary myocytes indicated that selenium supplementation or DNMT inhibitor AZA treatment reduced DNA methylation of the GPX1 gene promoter. Selenium supplementation and AZA administration showed synergic inhibitory effect on GPX1 gene promoter methylation. Conclusions. Selenium supplementation showed cardioprotective effects on AGE-induced heart failure by suppressing ROS-mediated myocyte apoptosis. Selenium supplementation suppressed ROS generation by increasing GPX1 expression via inhibiting DNMT2-induced GPX1 gene promoter DNA methylation in myocytes exposed to AGEs.

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6

Vivekanandan, Perumal, Hubert Darius-J. Daniel, Rajesh Kannangai, Francisco Martinez-Murillo e Michael Torbenson. "Hepatitis B Virus Replication Induces Methylation of both Host and Viral DNA". Journal of Virology 84, n. 9 (10 febbraio 2010): 4321–29. http://dx.doi.org/10.1128/jvi.02280-09.

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ABSTRACT Control of viral replication is a major therapeutic goal to reduce morbidity and mortality from chronic hepatitis B virus (HBV) infection. Recently, methylation has been identified as a novel host defense mechanism, and methylation of viral DNA leads to downregulation of HBV gene expression. To better understand the mechanisms of HBV methylation, cell lines were exposed to HBV using a model system that mimics natural infection and the expression of host DNA methyltransferase genes (DNMTs) was measured. DNMT1, DNMT2, and DNMT3 were all significantly upregulated in response to HBV. DNMT3 was further studied because of its known role in the de novo methylation of DNA. Cotransfection experiments with full-length HBV and DNMT3 led to the downregulation of viral protein and pregenomic RNA production. To investigate whether the upregulation of DNMTs could also have an effect on the methylation of host DNA, cell lines were exposed to HBV in two independent model systems, one that mimics natural infection and a second model with temporary transfection. Host DNA methylation was measured by DNA microarray analysis. Increased methylation of host CpG islands was detected in both experimental systems. Two CpG islands, corresponding to genes SUFU and TIRAP, were selected, and the downregulation of these genes in hepatocellular carcinomas was confirmed. In conclusion, hepatocytes respond to HBV infection by upregulating DNMTs. The DNMTs methylate viral DNA, leading to decreased viral gene expression and decreased viral replication. However, virus-induced overexpression of DNMTs also leads to methylation of host CpG islands.

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Huang, Zhi-Xuan, Jing Li, Qing-Ping Xiong, Hao Li, En-Duo Wang e Ru-Juan Liu. "Position 34 of tRNA is a discriminative element for m5C38 modification by human DNMT2". Nucleic Acids Research 49, n. 22 (6 dicembre 2021): 13045–61. http://dx.doi.org/10.1093/nar/gkab1148.

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Abstract Dnmt2, a member of the DNA methyltransferase superfamily, catalyzes the formation of 5-methylcytosine at position 38 in the anticodon loop of tRNAs. Dnmt2 regulates many cellular biological processes, especially the production of tRNA-derived fragments and intergenerational transmission of paternal metabolic disorders to offspring. Moreover, Dnmt2 is closely related to human cancers. The tRNA substrates of mammalian Dnmt2s are mainly detected using bisulfite sequencing; however, we lack supporting biochemical data concerning their substrate specificity or recognition mechanism. Here, we deciphered the tRNA substrates of human DNMT2 (hDNMT2) as tRNAAsp(GUC), tRNAGly(GCC) and tRNAVal(AAC). Intriguingly, for tRNAAsp(GUC) and tRNAGly(GCC), G34 is the discriminator element; whereas for tRNAVal(AAC), the inosine modification at position 34 (I34), which is formed by the ADAT2/3 complex, is the prerequisite for hDNMT2 recognition. We showed that the C32U33(G/I)34N35 (C/U)36A37C38 motif in the anticodon loop, U11:A24 in the D stem, and the correct size of the variable loop are required for Dnmt2 recognition of substrate tRNAs. Furthermore, mammalian Dnmt2s possess a conserved tRNA recognition mechanism.

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Lyko, Frank. "RNA Methylation and Its Role in the Hematopoietic System". Blood 130, Suppl_1 (7 dicembre 2017): SCI—52—SCI—52. http://dx.doi.org/10.1182/blood.v130.suppl_1.sci-52.sci-52.

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Abstract RNA methylation represents a novel expansion of traditional epigenetic concepts. RNAs can be methylated at adenine and at cytosine residues, and both modifications have distinct regulatory potential. Our work focuses on the DNMT2 enzyme, which is a member of the animal (cytosine-5) DNA methyltransferase family and has long been considered to function as a DNA methyltransferase. However, a DNA methyltransferase activity could not be confirmed conclusively and more recent work clearly demonstrates that DNMT2 is a tRNA methyltransferase. This unexpected substrate is interpreted to reflect an evolutionary ancient substrate switch from DNA to tRNA that expanded the epigenetic regulatory capacity of the DNMT family to also include RNA. To analyze the function of DNMT2, we performed a detailed analysis of knockout mice. These mice are viable and fertile, but also show a reduction of hematopoietic stem and progenitor cell populations and a cell-autonomous defect in their differentiation.1 RNA bisulfite sequencing revealed that Dnmt2 methylates C38 of tRNA Asp(GTC), Gly(GCC), and Val(AAC). Proteomic analyses from primary bone marrow cells uncovered systematic differences in protein expression that are due to specific codon mistranslation by tRNAs lacking DNMT2-dependent methylation. Together, these results illustrate the regulatory capacity of DNMT2-mediated tRNA methylation in genome recoding.2 Our current work addresses additional mechanistic aspects that link tRNA methylation to translational fidelity and investigates the relevance of DNMT2-mediated tRNA methylation for leukemogenesis. 1. Tuorto F, Herbst F, Alerasool N, et al. The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis. EMBO J. 2015;34(18):2350-2362. 2. Tuorto F, Lyko F. Genome recoding by tRNA modifications. Open Biol. 2016;6(12):160287. Disclosures No relevant conflicts of interest to declare.

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Goll, Mary Grace, Finn Kirpekar, Keith A. Maggert, Jeffrey A. Yoder, Chih-Lin Hsieh, Xiaoyu Zhang, Kent G. Golic, Steven E. Jacobsen e Timothy H. Bestor. "Methylation of tRNAAsp by the DNA Methyltransferase Homolog Dnmt2". Science 311, n. 5759 (20 gennaio 2006): 395–98. http://dx.doi.org/10.1126/science.1120976.

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The sequence and the structure of DNA methyltransferase-2 (Dnmt2) bear close affinities to authentic DNA cytosine methyltransferases. A combined genetic and biochemical approach revealed that human DNMT2 did not methylate DNA but instead methylated a small RNA; mass spectrometry showed that this RNA is aspartic acid transfer RNA (tRNAAsp) and that DNMT2 specifically methylated cytosine 38 in the anticodon loop. The function of DNMT2 is highly conserved, and human DNMT2 protein restored methylation in vitro to tRNAAsp from Dnmt2-deficient strains of mouse, Arabidopsis thaliana, and Drosophila melanogaster in a manner that was dependent on preexisting patterns of modified nucleosides. Indirect sequence recognition is also a feature of eukaryotic DNA methyltransferases, which may have arisen from a Dnmt2-like RNA methyltransferase.

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Bhattacharya, Tamanash, Danny W. Rice, John M. Crawford, Richard W. Hardy e Irene L. G. Newton. "Evidence of Adaptive Evolution in Wolbachia-Regulated Gene DNMT2 and Its Role in the Dipteran Immune Response and Pathogen Blocking". Viruses 13, n. 8 (27 luglio 2021): 1464. http://dx.doi.org/10.3390/v13081464.

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Eukaryotic nucleic acid methyltransferase (MTase) proteins are essential mediators of epigenetic and epitranscriptomic regulation. DNMT2 belongs to a large, conserved family of DNA MTases found in many organisms, including holometabolous insects such as fruit flies and mosquitoes, where it is the lone MTase. Interestingly, despite its nomenclature, DNMT2 is not a DNA MTase, but instead targets and methylates RNA species. A growing body of literature suggests that DNMT2 mediates the host immune response against a wide range of pathogens, including RNA viruses. Curiously, although DNMT2 is antiviral in Drosophila, its expression promotes virus replication in mosquito species. We, therefore, sought to understand the divergent regulation, function, and evolution of these orthologs. We describe the role of the Drosophila-specific host protein IPOD in regulating the expression and function of fruit fly DNMT2. Heterologous expression of these orthologs suggests that DNMT2′s role as an antiviral is host-dependent, indicating a requirement for additional host-specific factors. Finally, we identify and describe potential evidence of positive selection at different times throughout DNMT2 evolution within dipteran insects. We identify specific codons within each ortholog that are under positive selection and find that they are restricted to four distinct protein domains, which likely influence substrate binding, target recognition, and adaptation of unique intermolecular interactions. Collectively, our findings highlight the evolution of DNMT2 in Dipteran insects and point to structural, regulatory, and functional differences between mosquito and fruit fly homologs.

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Tesi sul tema "DNMT2"

1

Müller, Sara [Verfasser]. "Biologische Funktionsanalyse und Identifizierung neuer Substrate der Methyltransferase Dnmt2 / Sara Müller". Kassel : Universitätsbibliothek Kassel, 2012. http://d-nb.info/101926845X/34.

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Kiani, Jafar. "Hérédité épigénétique et méthylation des ARNs : rôle de la méthyltransférase Dnmt2". Nice, 2011. http://www.theses.fr/2011NICE4093.

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Epigenetics deals with heritable alterations in gene expression that is not based on changes n DNA sequence. It was thought that DNA methylation and chromatin-encoded epigenetic information were the only epigenetic marks transmitted to the following generations. Recently, our group described the role of RNA in hereditary epigenetic variation, paramutation in mice. The role of RNA was demonstrated by the establishment of a heritable phenotype following microinjection into one-cell embryos of Kit heterozygous sperm RNA. It was further confirmed by induction of hereditary phenotypes after microinjection of an oligoribonucleotide with a Kit RNA sequence or small noncoding RNAs (miR-222 and miR-124). We now report that, Dnmt2, a RNA methyltransferase, is required for induction by small non-coding RNAs of hereditaty epigenetic variation of expression of the Kit and Sox9 genes, inactivation of the Dnmt2 gene precluded their occurrence. Kit* paramutants, which maintain a mutant phenotype with a Kit+/+ genotype, were not observed in the progeny of crosses between Dnmt2-/- Kittm1al∫+ heterozygotes, no were they generated by microinjection in fertilized eggs of RNAs of the Dnmt2-negative Kit heterozygotes. The Sox9 “giant” phenotype was similary not generated by miR-124 RNA in Dnmt2-/- embryos. Interaction of the Dnmt2 protein with Kit RNA was evidenced by co-immunoprecipitation assays. Bisulfite sequencing assays detected Dnmt2-dependent cytosine methylation in Kit RNA, exclusively in embryos undergoing the modification. RNA methylation effected by Dnmt2 appears as a key feature of the induction of epigenetic variations by non-coding RNAs. In the other hand, growing evidence indicates thet ncRNAs play a key role in regulation of basal transcription machinery. Several studies have recently revealed that noncoding RNAs such as B2RNA, 7SK and U1 snRNA are involved in the regulation of CTD phosphorylation of RNA polymerase II by modulating kinase activity of Cyclin H/T1. Here we reported cardiac hypertrophy in Dnmt2 mutant mice which is accompanied by enhanced activity of RNA polymerase II. Our results showed significant changes in the expression profiles of B2 RNA abd ASK in wild type compare to Dnmt2 mutant mice. In this study, we are attempting to determine that methyl transferase activity of Dnmt2 has a potential role in epigenetic inheritance and pathology.

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Schuster, Isabelle [Verfasser]. "Strukturelle und funktionelle Charakterisierung des Dnmt2-Homologs DnmA von Dictyostelium discoideum / Isabelle Schuster". Kassel : Universitätsbibliothek Kassel, 2016. http://d-nb.info/1101616091/34.

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Hartmann, Mark [Verfasser], e Frank [Akademischer Betreuer] Lyko. "Centromeric tRNA and Dnmt2-mediated Methylation in Mitotic Chromosome Segregation / Mark Hartmann ; Betreuer: Frank Lyko". Heidelberg : Universitätsbibliothek Heidelberg, 2018. http://d-nb.info/1177148862/34.

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Durdevic, Zeljko [Verfasser], e Frank [Akademischer Betreuer] Lyko. "Characterization of the Biological Function of Dnmt2 in Drosophila melanogaster / Zeljko Durdevic ; Betreuer: Frank Lyko". Heidelberg : Universitätsbibliothek Heidelberg, 2013. http://d-nb.info/1177249774/34.

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Kaiser, Steffen [Verfasser]. "Investigations on DNA methylation by Dnmt2 and impact of tRNA modifications on TLR7 stimulation / Steffen Kaiser". Mainz : Universitätsbibliothek Mainz, 2015. http://d-nb.info/1080401431/34.

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Shanmugam, Raghuvaran [Verfasser], e Albert [Akademischer Betreuer] Jeltsch. "Biochemical characterisation of tRNA-Asp methyltransferase Dnmt2 and its physiological significance / Raghuvaran Shanmugam. Betreuer: Albert Jeltsch". Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2014. http://d-nb.info/1049931661/34.

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Vieira, Gilberto Cavalheiro. "Modelagem molecular e imunodetecção de DNA Metiltransferases 2 de Drosofilídeos : uma abordagem evolutiva da enigmática DNMT2". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/117889.

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A metilação do DNA genômico é um dos principais mecanismos de regulação epigenética nos organismos. Dentre as diferentes classes de DNA MTase, as m5C-MTase são as que se distribuem amplamente de procariotos a eucariotos. Em vertebrados existem três diferentes famílias: DNMT1, DNMT2 e DNMT3a e 3b. A DNMT1 possui atividade junto ao DNA hemimetilado. As DNMT3a e 3b são responsáveis pela metilação de novo. Já a subfamília DNMT2 possui seus sítios catalíticos altamente conservados, desde procariotos até eucariotos, possuindo propriedades que permitem executar funções tanto de metilação de novo, assim como de manutenção de metilação. Além disso, as enzimas da família DNMT2 podem atuar metilando citosinas genômicas ou de tRNAs. Em mamíferos, invertebrados e plantas a DNMT2 é classificada, prioritariamente in vivo como uma tRNA MTase. Entretanto, já foi descrita atividade de DNA MTase por parte dessas enzimas, mesmo que em baixos níveis. O que se discute são as atividades preferenciais da DNMT2 e os mecanismos que modulam sua atividade, pois se reconhece que em organismos que não possuem as MTases canônicas (DNMT1 e DNMT3), mas apresentam metilação em seu genoma, é a DNMT2 que atua como MTase em ambos os substratos. Espécies de Drosophila são conhecidas como de Dnmt2-only, justamente por possuírem apenas a DNMT2 na função de metilação de citosinas. A importância de seu papel no âmbito ecológico e evolutivo nesse grupo de espécies se reflete na presença de fenômenos peculiares, como a metilação sexo-específica presente em espécies do subgrupo willistoni de Drosophila, descrito por nosso grupo de pesquisa. No presente trabalho realizou-se a modelagem das enzimas DNMT2 de D. melanogaster, D. willistoni e Mus musculus com diferentes metodologias. A partir desses modelos realizaram-se análises comparativas com as estruturas cristalográficas de DNMT2 depositadas no banco de dados PDB, com o objetivo de estabelecer as relações evolutivas e funcionais entre as diferentes enzimas. Adicionalmente, de posse de modelos de DNMT2 - de validada qualidade - de duas espécies pertencentes a diferentes grupos evolutivos de drosofilídeos, realizaram-se estudos de caracterização evolutiva e estrutural das 22 espécies que tiveram seus genomas sequenciados e depositados no bando de dados Flybase, somando-se a essas a sequência de DNMT2 de Drosophila tropicalis (subgrupo willistoni), sequenciado por nosso grupo de pesquisa. Os resultados das análises evolutivas e estruturais sugerem propriedades diferenciais entre as DNMT2 de espécies do subgrupo willistoni em relação às demais. Estes resultados indicam que mesmo em espécies que possuem relações evolutivas próximas possam ocorrer mecanismos adaptativos que estabeleçam gradações na afinidade das DNMT2 por diferentes substratos, sem que para isso ocorram drásticas mudanças na arquitetura da enzima.
The methylation of genomic DNA is a major mechanism of epigenetic regulation in organisms. Among the different classes of DNA MTase the M5C-MTase are as widely distributed in prokaryotes to eukaryotes. In vertebrates there are three different families: DNMT1, DNMT2 and DNMT3a and 3b. The DNMT1 has activity with the hemimethylated DNA. The DNMT3a and 3b are responsible for de novo methylation. While the DNMT2 subfamily has its catalytic sites highly conserved from prokaryotes to eukaryotes, having properties that allow performing functions of both de novo and maintenance methylation. Furthermore, the DNMT2 family can act methylating cytokines, tRNAs or DNA. In mammals, invertebrates and plants, DNMT2 is classified primarily in vivo as a tRNA MTase. However,DNA-MTase activity by these enzymes has been described, even at low levels. The question is the preferred activities of DNMT2 and mechanisms that modulate its activity, because in organisms that do not have the canonical DNA-MTases (DNMT1 and DNMT3), but have cytokines methylated in its genome, the DNMT2 acts as MTase on both substrates. Drosophila species are known as Dnmt2-only. The importance of DNMT2’s role in ecological and evolutionary context in this species group is reflected by presence of a peculiar phenomenon: the sex-specific methylation described by our research group, presents in willistoni subgroup of Drosophila. In this study, DNMT2 of D. melanogaster, D. willistoni and Mus musculus were modeled by different methodologies. comparative analyzes with the crystallographic DNMT2 structures deposited in the PDB database were performed from these models, in order to establish the evolutionary and functional relationships between the different enzymes. Additionally, evolutionary and structural characterization studies of the 22 species, with the validated DNMT2 models of two species belonging to different evolutionary drosophilids groups, were conducted that have had their genomes sequenced and deposited in FlyBase data pack, adding the DNMT2 sequence of Drosophila tropicalis (willistoni subgroup) sequenced by our research group. The results of evolutionary and structural analyzes suggest differences between the DNMT2 properties of subgroup willistoni species from the other drosophilids. These results indicate that even species that have close evolutionary relationships may have adaptive mechanisms that establish gradations of DNMT2 affinity for different substrates, without the need of drastic changes in enzyme architecture.

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Liebers, Reinhard Kai [Verfasser], e Frank [Akademischer Betreuer] Lyko. "Dnmt2 in RNA methylation, RNA inheritance, and environmental responses in the mouse / Reinhard Kai Liebers ; Betreuer: Frank Lyko". Heidelberg : Universitätsbibliothek Heidelberg, 2016. http://d-nb.info/1180614186/34.

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Liebers, Reinhard [Verfasser], e Frank [Akademischer Betreuer] Lyko. "Dnmt2 in RNA methylation, RNA inheritance, and environmental responses in the mouse / Reinhard Kai Liebers ; Betreuer: Frank Lyko". Heidelberg : Universitätsbibliothek Heidelberg, 2016. http://d-nb.info/1180614186/34.

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Capitoli di libri sul tema "DNMT2"

1

Arnemann, J. "DNA-Methyltransferase (DNMT)". In Springer Reference Medizin, 718. Berlin, Heidelberg: Springer Berlin Heidelberg, 2019. http://dx.doi.org/10.1007/978-3-662-48986-4_3463.

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Arnemann, J. "DNA-Methyltransferase (DNMT)". In Lexikon der Medizinischen Laboratoriumsdiagnostik, 1. Berlin, Heidelberg: Springer Berlin Heidelberg, 2018. http://dx.doi.org/10.1007/978-3-662-49054-9_3463-1.

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Yildiz, Can Bora, e Geraldine Zimmer-Bensch. "Role of DNMTs in the Brain". In Advances in Experimental Medicine and Biology, 363–94. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-11454-0_15.

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Tajima, Shoji, Isao Suetake, Kohei Takeshita, Atsushi Nakagawa e Hironobu Kimura. "Domain Structure of the Dnmt1, Dnmt3a, and Dnmt3b DNA Methyltransferases". In Advances in Experimental Medicine and Biology, 63–86. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-43624-1_4.

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Tajima, Shoji, Isao Suetake, Kohei Takeshita, Atsushi Nakagawa, Hironobu Kimura e Jikui Song. "Domain Structure of the Dnmt1, Dnmt3a, and Dnmt3b DNA Methyltransferases". In Advances in Experimental Medicine and Biology, 45–68. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-11454-0_3.

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Amruth Maroju, Pranay, e Kommu Naga Mohan. "DNA Methyltransferases and Schizophrenia: Current Status". In Psychosis - Phenomenology, Psychopathology and Pathophysiology [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.98567.

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Abstract (sommario):

Schizophrenia (SZ) is a complex disorder without a single cause but with multiple etiologies. Monozygotic twin studies suggesting high discordant rates provide evidence for epigenetic mechanisms among the factors that result in increased susceptibility. Among the different epigenetic modifications in mammals, DNA methylation mediated by DNA methyltransferases (DNMTs) is the most-well studied. Studies on post-mortem brain samples and blood samples of SZ patients revealed altered levels of most DNMTs. In addition, some recent studies also reported disease-associated SNPs in the DNMT genes. While the effects of dysregulation of DNMTs are beginning to be understood, many unanswered questions remain. Here, we review the current evidences that shed light on the relationship between DNMT dysregulation and SZ, and suggest the possible strategies to address some of the unanswered questions.

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Svedružić, Željko M. "Dnmt1". In Progress in Molecular Biology and Translational Science, 221–54. Elsevier, 2011. http://dx.doi.org/10.1016/b978-0-12-387685-0.00006-8.

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"DNMTs". In Encyclopedia of Cancer, 1147. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-16483-5_1698.

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"Methyltransferase, DNA (dnmt1, dnmt1-b, 19p13.3-p13.2)". In Encyclopedia of Genetics, Genomics, Proteomics and Informatics, 1201. Dordrecht: Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6754-9_10292.

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Sharif, Jafar, e Haruhiko Koseki. "Recruitment of Dnmt1". In Progress in Molecular Biology and Translational Science, 289–310. Elsevier, 2011. http://dx.doi.org/10.1016/b978-0-12-387685-0.00008-1.

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Atti di convegni sul tema "DNMT2"

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Laranjeira, Angelo B., Erich Huang, Larry Rubinstein, Dat Nguyen e Sherry X. Yang. "Abstract 3847: Knockout of DNMT1 using CRISPR gene-editing technology confers resistance to DNMT inhibitors in human breast cancer cells". In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-3847.

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Laranjeira, Angelo B., Erich Huang, Larry Rubinstein, Dat Nguyen e Sherry X. Yang. "Abstract 3847: Knockout of DNMT1 using CRISPR gene-editing technology confers resistance to DNMT inhibitors in human breast cancer cells". In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-3847.

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Cai, Yi, Hsing-chen Tsai, Ray-whay Yen, Limin Xia, Yang Zhang e Stephen Baylin. "Abstract LB-150: Genetic depletion of DNMT1 reveals a DNMT1 threshold controlling DNA methylation in human cells". In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-lb-150.

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Laranjeira, Angelo B., Dat Nguyen, Erich Huang, James H. Doroshow e Sherry X. Yang. "Abstract 5081: Disruption of DNA methyltransferase (DNMT) 1 confers resistance to DNMT inhibitors in human colorectal cancer cells". In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-5081.

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Ferreira, Nancy, Darley Ferreira e Thais Ferreira. "GENETIC EVALUATION OF MICROCALCIFICATIONS AS A PROGNOSTIC FACTOR". In Abstracts from the Brazilian Breast Cancer Symposium - BBCS 2021. Mastology, 2021. http://dx.doi.org/10.29289/259453942021v31s2101.

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Introduction: Breast cancer is the most recurring type of cancer among women, with reduced mortality at an initial stage of lesion. From a radiological perspective, perceived microcalcifications may be associated with histological findings such as proliferative injuries with or without atypical features and ductal carcinoma in situ. Currently, percutaneous and vacuum biopsies allow for the correlation between anatomoradiological and identification of previous lesions and those that offer the risk of cancer. No biomarker has been established to predict the risk of cancer in women diagnosed with benign mammary disease. Doing so could strengthen the possibility of stratifying the individual risk of benign injuries for cancer. The platelet-derived growth factor receptor A (PDGFRA) plays its part in tumor oncogenesis, angiogenesis, and metastasis, and its activation is found in some kinds of cancer. In contrast, DNA methylation standards are initial changes to the development of cancer and may be helpful in its early identification, being regulated by a family of enzymes called DNMTs (DNA methyltransferase). Methods: The aim of this study was to evaluate the profile of BI-RADS® 4 and 5 mammary microcalcification women carriers and determine the level of the gene expression of possible molecular markers in 37 patients with mammary microcalcification (paraffin blocks) and 26 patients with breast cancer (fresh in RNA later tissue) cared for at the Hospital Barão de Lucena’s Mastology Ambulatory. Anatomoradiological aspects along with clinical findings have been evaluated , and percentage rates have been calculated. The PDGFRA and DNMTs (DMNT3a) gene expressions have been established using quantitative polymerase chain reaction (qPCR), with the use of β-actin as reference gene. Discussion: In the patients with mammary microcalcification, the average age was 55.9; predominantly whiteskinned subjects (p<0.014). Most of them were mothers (p<0.001), and the average menarche age was 13. The subgroups that presented greater significance were patients classified BI-RADS® in category IV (67.6%) and histological findings of nonproliferative lesion (p<0.001). Lesions of the ductal carcinoma in situ type (100%) presented positive estrogen and progesterone receptors, and 94.6% have undergone sectorectomy surgery by prior needling (p<0.001). The most damaged breast was the left one (62.2%), and the most affected quadrant was the top lateral one (59.5%) (p<0.001). There was no family history in 83.8% of the cases. In the tested microcalcification samples, it was not possible to observe the expression of PDGFRA. Nevertheless, 15 out of 37 patients with microcalcification showed an increase in the gene expression of DMNT3a, most of them greater than Luminal and triple-negative cancer types. Conclusion: The data presented here highlight the improvement on the description of BI-RADS® 4 subclassification in order to better conduct the clinical decision and also demonstrated the potential of DNMTs evaluation in microcalcification samples as a strategy to access the understanding about the role of these molecules in the breast cancer development.

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SILVA, CAMILA T. DA, Fernanda Molognoni, Fabiana H. M. de Melo e Miriam Galvonas Jasiulionis. "Abstract 426: Transcriptional regulation of dnmt1 by E2F1 in melanoma progression". In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-426.

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Lee, Gun Eui, e Keith D. Robertson. "Abstract 1054: The role of DNMT1 in the DNA damage response". In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-1054.

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Martínez Fernández, Liliam, e Jose Luis Medina Franco. "Identification of novel DNA Methyltransferase 1 (DNMT1) inhibitors from focused databases". In 7th International Electronic Conference on Medicinal Chemistry. Basel, Switzerland: MDPI, 2021. http://dx.doi.org/10.3390/ecmc2021-11570.

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Tohme, Rita, Francis Enane, Caroline Schuerger, Xiaorong Gu, Melissa Fishel, John Pink, Daniel Lindner, Davendra Sohal e Yogen Saunthararajah. "Abstract 1088: Advancing non-cytotoxic DNMT1-targeting to treat chemorefractory pancreatic cancer". In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-1088.

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Endo, Kanenori, Takanori Miyake, Soichiro Honjo, Shunichi Tsujitani, Yasuaki Hirooka e Masahide Ikeguchi. "Abstract 185: Protein expression of DNMT1, DNMT3a, and DNMT3b in human hepatocellular carcinoma". In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-185.

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Rapporti di organizzazioni sul tema "DNMT2"

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Sarkisova, Karine, A. Gabova, E. Fedosova, A. Shatskova, M. Rudenok, V. Stanishevskaya, M. Shadrina e P. Slominsky. Maternal methyl-enriched diet reduces absence seizures and depression-like comorbidity, and increases DNMT1 and HCN1 gene expression in the somatosensory cortex in adult offspring. LLC MAKS Press, giugno 2020. http://dx.doi.org/10.29003/m1395.fens-2020.

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