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1

MUND, Cora, Tanja MUSCH, Martin STRÖDICKE, Birte ASSMANN, En LI, and Frank LYKO. "Comparative analysis of DNA methylation patterns in transgenic Drosophila overexpressing mouse DNA methyltransferases." Biochemical Journal 378, no. 3 (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. Quantitativ
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Liu, Kui, Yun Fei Wang, Carmen Cantemir, and 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, no. 8 (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 pre
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3

Del Castillo Falconi, Victor M., Karla Torres-Arciga, Genaro Matus-Ortega, José Díaz-Chávez, and Luis A. Herrera. "DNA Methyltransferases: From Evolution to Clinical Applications." International Journal of Molecular Sciences 23, no. 16 (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, protis
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Papakonstantinou, Efthymia, Ioanna Pappa, Georgios Androutsopoulos, Georgios Adonakis, Ioannis Maroulis, and Vasiliki Tzelepi. "Comprehensive Analysis of DNA Methyltransferases Expression in Primary and Relapsed Ovarian Carcinoma." Cancers 15, no. 20 (2023): 4950. http://dx.doi.org/10.3390/cancers15204950.

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Background: Despite recent advances in epithelial ovarian carcinoma (EOC) treatment, its recurrence and mortality rates have not improved significantly. DNA hypermethylation has generally been associated with an ominous prognosis and chemotherapy resistance, but the role of DNA methyltransferases (DNMTs) in EOC remains to be investigated. Methods: In the current study, we systematically retrieved gene expression data from patients with EOC and studied the immunohistochemical expression of DNMTs in 108 primary and 26 relapsed tumors. Results: Our results showed that the DNMT1, DNMT3A, DNMT3B an
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KIM, SEON-HEE, HYE-JEONG CHO, WOON-MOK SOHN, et al. "Egg-specific expression of protein with DNA methyltransferase activity in the biocarcinogenic liver fluke Clonorchis sinensis." Parasitology 142, no. 9 (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 considera
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Zhu, Huolan, Xiang Wang, Xuyang Meng, 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 (April 6, 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
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Huang, Zhi-Xuan, Jing Li, Qing-Ping Xiong, Hao Li, En-Duo Wang, and Ru-Juan Liu. "Position 34 of tRNA is a discriminative element for m5C38 modification by human DNMT2." Nucleic Acids Research 49, no. 22 (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,
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Vivekanandan, Perumal, Hubert Darius-J. Daniel, Rajesh Kannangai, Francisco Martinez-Murillo, and Michael Torbenson. "Hepatitis B Virus Replication Induces Methylation of both Host and Viral DNA." Journal of Virology 84, no. 9 (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. DNMT
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9

Lyko, Frank. "RNA Methylation and Its Role in the Hematopoietic System." Blood 130, Suppl_1 (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 reflec
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10

Goll, Mary Grace, Finn Kirpekar, Keith A. Maggert, et al. "Methylation of tRNAAsp by the DNA Methyltransferase Homolog Dnmt2." Science 311, no. 5759 (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 m
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11

Bhattacharya, Tamanash, Danny W. Rice, John M. Crawford, Richard W. Hardy, and 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, no. 8 (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 antiv
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Dev, Rachana Roshan, Rakesh Ganji, Satya Prakash Singh, Sundarasamy Mahalingam, Sharmistha Banerjee, and Sanjeev Khosla. "Cytosine methylation by DNMT2 facilitates stability and survival of HIV-1 RNA in the host cell during infection." Biochemical Journal 474, no. 12 (2017): 2009–26. http://dx.doi.org/10.1042/bcj20170258.

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The enigmatic methyltransferase, DNMT2 (DNA methyltransferase 2), structurally resembles a DNA methyltransferase, but has been shown to be a tRNA methyltransferase targeting cytosine within a specific CpG in different tRNA molecules. We had previously shown that, during environmental stress conditions, DNMT2 is re-localized from the nucleus to the cytoplasmic stress granules (SGs) and is associated with RNA-processing proteins. In the present study, we show that DNMT2 binds and methylates various mRNA species in a sequence-independent manner and gets re-localized to SGs in a phosphorylation-de
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13

Bhattacharya, Tamanash, Liewei Yan, John M. Crawford, Hani Zaher, Irene L. G. Newton, and Richard W. Hardy. "Differential viral RNA methylation contributes to pathogen blocking in Wolbachia-colonized arthropods." PLOS Pathogens 18, no. 3 (2022): e1010393. http://dx.doi.org/10.1371/journal.ppat.1010393.

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Arthropod endosymbiont Wolbachia pipientis is part of a global biocontrol strategy to reduce the replication of mosquito-borne RNA viruses such as alphaviruses. We previously demonstrated the importance of a host cytosine methyltransferase, DNMT2, in Drosophila and viral RNA as a cellular target during pathogen-blocking. Here we report a role for DNMT2 in Wolbachia-induced alphavirus inhibition in Aedes species. Expression of DNMT2 in mosquito tissues, including the salivary glands, is elevated upon virus infection. Notably, this is suppressed in Wolbachia-colonized animals, coincident with re
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14

Yu, Tian, Yeming Xie, Chong Tang, et al. "Dnmt2-null sperm block maternal transmission of a paramutant phenotype†." Biology of Reproduction 105, no. 3 (2021): 603–12. http://dx.doi.org/10.1093/biolre/ioab086.

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Abstract Previous studies have shown that Dnmt2-null sperm block the paternal transmission (through sperm) of certain acquired traits, e.g., high-fat diet–induced metabolic disorders or white tails due to a Kit paramutation. Here, we report that DNMT2 is also required for the transmission of a Kit paramutant phenotype (white tail tip) through the female germline (i.e., oocytes). Specifically, ablation of Dnmt2 led to aberrant profiles of tRNA-derived small RNAs (tsRNAs) and other small noncoding RNAs (sncRNAs) in sperm, which correlate with altered mRNA transcriptomes in pronuclear zygotes der
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15

Schaefer, Matthias, and Frank Lyko. "Solving the Dnmt2 enigma." Chromosoma 119, no. 1 (2009): 35–40. http://dx.doi.org/10.1007/s00412-009-0240-6.

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16

Chen, Zhiyuan, and Yi Zhang. "Role of Mammalian DNA Methyltransferases in Development." Annual Review of Biochemistry 89, no. 1 (2020): 135–58. http://dx.doi.org/10.1146/annurev-biochem-103019-102815.

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DNA methylation at the 5-position of cytosine (5mC) plays vital roles in mammalian development. DNA methylation is catalyzed by DNA methyltransferases (DNMTs), and the two DNMT families, DNMT3 and DNMT1, are responsible for methylation establishment and maintenance, respectively. Since their discovery, biochemical and structural studies have revealed the key mechanisms underlying how DNMTs catalyze de novo and maintenance DNA methylation. In particular, recent development of low-input genomic and epigenomic technologies has deepened our understanding of DNA methylation regulation in germ lines
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17

McCall, Jamie L., Ivan Martinez, and John B. Barnett. "Paternal cadmium exposure decreases DMNT2 expression and increases obesity in male offspring." Journal of Immunology 210, no. 1_Supplement (2023): 66.08. http://dx.doi.org/10.4049/jimmunol.210.supp.66.08.

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Abstract Prenatal exposure to toxic agents, including cadmium (Cd), can alter offspring immune cell development and function. As Cd does not readily cross the placenta, it is hypothesized that prenatal Cd alters the epigenetic programming of genes including non-coding RNAs (ncRNAs). We found that prenatal Cd exposure increases CD4 +T cell proliferation following activation and that this phenotype is dependent on the upregulation of an oncogenic long non-coding RNA (lncRNA) known as small nucleolar RNA host gene 7 (lncSnhg7). In our previous studies, both parents were exposed. To determine the
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18

Wong, Kah Keng, Charles H. Lawrie, and Tina M. Green. "Oncogenic Roles and Inhibitors of DNMT1, DNMT3A, and DNMT3B in Acute Myeloid Leukaemia." Biomarker Insights 14 (January 2019): 117727191984645. http://dx.doi.org/10.1177/1177271919846454.

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Epigenetic alteration has been proposed to give rise to numerous classic hallmarks of cancer. Impaired DNA methylation plays a central role in the onset and progression of several types of malignancies, and DNA methylation is mediated by DNA methyltransferases (DNMTs) consisting of DNMT1, DNMT3A, and DNMT3B. DNMTs are frequently implicated in the pathogenesis and aggressiveness of acute myeloid leukaemia (AML) patients. In this review, we describe and discuss the oncogenic roles of DNMT1, DNMT3A, and DNMT3B in AML. The clinical response predictive roles of DNMTs in clinical trials utilising hy
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Kapopara, Ravi, S. Prasanth Kumar, S. K. Patel, et al. "Virtual screening of natural bioactives in combating cancer through epigenetic modulation." South Asian Journal of Experimental Biology 1, no. 5 (2011): 12–16. http://dx.doi.org/10.38150/sajeb.1(5).p12-16.

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Epigenetic events are due to altered gene expression without any changes inthe genetic material and characteristic of heritability via cell division. Theimpact of epigenetic control over cancer is one among the thrust area ofresearch in cancer biology. The present study deals about the virtual screeningof plant derived bioactives, directed against the key molecular regulatorsof the epigenetic events viz. DNA methyltransferases (DNMT1, DNMT2 andDNMT3B), Histone acetyltransferase (HAT), Histone deacetylase 8 (HDAC8),Histone H3 lysine 27 methyl transferase (H3K27MT) and Histone H3 specificlysi
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Ding, Y. B., J. L. He, X. Q. Liu, X. M. Chen, C. L. Long, and Y. X. Wang. "Expression of DNA methyltransferases in the mouse uterus during early pregnancy and susceptibility to dietary folate deficiency." REPRODUCTION 144, no. 1 (2012): 91–100. http://dx.doi.org/10.1530/rep-12-0006.

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We have characterized the uterine expression of DNA methyltransferases (DNMTs) during early pregnancy in mice and determined whether a folate-deficient diet (FDD) can affect DNMTs in this context. Within endometrial cells, expressions of DNMT (cytosine-5) 1 (Dnmt1),Dnmt3a, andDnmt3bwere significantly elevated during the prereceptive phase of pregnancy but generally returned to baseline levels during receptive and postimplantation periods. As such, the transcription of DNMT genes is temporally regulated during early pregnancy. When comparisons were made between implantation sites (IS) and inter
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Park, Min-Ji, Woon-Mok Sohn, and Young-An Bae. "Genome-wide identification of histone lysine methyltransferases and their implications in the epigenetic regulation of eggshell formation-related genes in a trematode parasite Clonorchis sinensis." Parasites, Hosts and Diseases 62, no. 1 (2024): 98–116. http://dx.doi.org/10.3347/phd.23116.

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Epigenetic writers including DNA and histone lysine methyltransferases (DNMT and HKMT, respectively) play an initiative role in the differentiation and development of eukaryotic organisms through the spatiotemporal regulation of functional gene expressions. However, the epigenetic mechanisms have long been suspected in helminth parasites lacking the major DNA methyltransferases DNMT1 and DNMT3a/3b. Very little information on the evolutionary status of the epigenetic tools and their role in regulating chromosomal genes is currently available in the parasitic trematodes. We previously suggested
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Schulz, Eike C., Heide M. Roth, Serge Ankri, and Ralf Ficner. "Structure Analysis of Entamoeba histolytica DNMT2 (EhMeth)." PLoS ONE 7, no. 6 (2012): e38728. http://dx.doi.org/10.1371/journal.pone.0038728.

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23

Zimmermann, Nicole, Jürgen Zschocke, Tatjana Perisic, Shuang Yu, Florian Holsboer, and Theo Rein. "Antidepressants inhibit DNA methyltransferase 1 through reducing G9a levels." Biochemical Journal 448, no. 1 (2012): 93–102. http://dx.doi.org/10.1042/bj20120674.

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The discovery of epigenetic processes as possible pivotal regulatory mechanisms in psychiatric diseases raised the question of how psychoactive drugs may impact the epigenetic machinery. In the present study we set out to explore the specificity and the mode of action of the reported inhibitory effect of the TCA (tricyclic antidepressant) amitriptyline on DNMT (DNA methyltransferase) activity in primary astrocytes from the rat cortex. We found that the impact on DNMT was shared by another TCA, imipramine, and by paroxetine, but not by venlafaxine or the mood stabilizers carbamazepine and valpr
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Koul, Hari K., Mousa Vatanmakanian, Ellen Nogueira Lima, Lakshmi S. Chaturvedi, and Sweaty K. Koul. "DNA methyl-transferases (DNMTs) as potential therapeutic vulnerability in prostate cancer." Journal of Clinical Oncology 42, no. 4_suppl (2024): 339. http://dx.doi.org/10.1200/jco.2024.42.4_suppl.339.

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339 Background: Prostate cancer (PCa) presents a significant health challenge in men, with a substantial number of deaths attributed to resistance to current Androgen Receptor inhibitors, and emergence of CRPC-adeno, CRPC-NEPC and CRPC-DNPC phenotypes. There is an urgent and unmet need for developing new targets for CRPC especially CRPC-NEPC and CRPC-DNPC. Because cellular plasticity plays a central role in transition to NEPC and DNPC, molecular targets that are critical for prostate cancer cellular plasticity could serve as actionable targets in therapy resistance in prostate cancer. In this
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Hopfer, Olaf J., Martina Komor, Ina S. Koehler, et al. "Expression of DNMT Isoforms Is Differentially Associated with Aberrant Promotor Methylation in MDS Hematopoietic Progenitor Cells during Lineage Specific Differentiation." Blood 108, no. 11 (2006): 2628. http://dx.doi.org/10.1182/blood.v108.11.2628.2628.

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Abstract Recent findings suggest that in myelodysplastic syndrome (MDS) several key regulatory genes are affected by aberrant promotor methylation. To explore the molecular basis of this impairment we have generated an in vitro model of MDS lineage-specific hematopoietic differentiation by culturing CD34+ cells from healthy donors (n=7) and MDS patients (low risk: RA/n=6, RARS/n=3; high risk: RAEB/n=4, RAEB-T/n=2) with EPO, TPO and GCSF. Cell harvest was at days 0, 4, 7 and 11. Promotor methylation analysis of key genes involved in the control of apoptosis (p73, survivin, DAPK), DNA-repair (hM
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Khan, Shagufta, Divya Tej Sowpati, Arumugam Srinivasan, Mamilla Soujanya, and Rakesh K. Mishra. "Long-Read Genome Sequencing and Assembly of Leptopilina boulardi: A Specialist Drosophila Parasitoid." G3: Genes|Genomes|Genetics 10, no. 5 (2020): 1485–94. http://dx.doi.org/10.1534/g3.120.401151.

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Leptopilinaboulardi (Hymenoptera: Figitidae) is a specialist parasitoid of Drosophila. The Drosophila-Leptopilina system has emerged as a suitable model for understanding several aspects of host-parasitoid biology. However, a good quality genome of the wasp counterpart was lacking. Here, we report a whole-genome assembly of L. boulardi to bring it in the scope of the applied and fundamental research on Drosophila parasitoids with access to epigenomics and genome editing tools. The 375Mb draft genome has an N50 of 275Kb with 6315 scaffolds >500bp and encompasses >95% complete BUSCOs. Usin
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Katoh, Mariko, Tomaz Curk, Qikai Xu, Blaz Zupan, Adam Kuspa, and Gad Shaulsky. "Developmentally Regulated DNA Methylation in Dictyostelium discoideum." Eukaryotic Cell 5, no. 1 (2006): 18–25. http://dx.doi.org/10.1128/ec.5.1.18-25.2006.

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ABSTRACT Methylation of cytosine residues in DNA plays a critical role in the silencing of gene expression, organization of chromatin structure, and cellular differentiation of eukaryotes. Previous studies failed to detect 5-methylcytosine in Dictyostelium genomic DNA, but the recent sequencing of the Dictyostelium genome revealed a candidate DNA methyltransferase gene (dnmA). The genome sequence also uncovered an unusual distribution of potential methylation sites, CpG islands, throughout the genome. DnmA belongs to the Dnmt2 subfamily and contains all the catalytic motifs necessary for cytos
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AlAmeer, Areej, and Samar Sultan. "Global DNA Methylation and DNA Methyltransferase Status Among Cigarette Smokers in Saudi." Life 15, no. 2 (2025): 171. https://doi.org/10.3390/life15020171.

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Smoking is a serious public health concern worldwide. It is a common environmental factor causing epigenetic alterations. This study aimed to explore the effect of smoking on DNA methylation by quantifying global DNA methylation, measuring the concentrations of plasma DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) among cigarette smokers in Saudi, and comparing these results with those of nonsmokers. Whole blood specimens were collected from Saudi cigarette smokers (n = 36) and non-smokers as controls (n = 36). Global DNA alteration was determined by a 5-methylation Cytosine (5-mC) colorim
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Raddatz, G., P. M. Guzzardo, N. Olova, et al. "Dnmt2-dependent methylomes lack defined DNA methylation patterns." Proceedings of the National Academy of Sciences 110, no. 21 (2013): 8627–31. http://dx.doi.org/10.1073/pnas.1306723110.

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Zimmermann, Robert A., Tim R. Fischer, Marvin Schwickert, Zarina Nidoieva, Tanja Schirmeister, and Christian Kersten. "Chemical Space Virtual Screening against Hard-to-Drug RNA Methyltransferases DNMT2 and NSUN6." International Journal of Molecular Sciences 24, no. 7 (2023): 6109. http://dx.doi.org/10.3390/ijms24076109.

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Targeting RNA methyltransferases with small molecules as inhibitors or tool compounds is an emerging field of interest in epitranscriptomics and medicinal chemistry. For two challenging RNA methyltransferases that introduce the 5-methylcytosine (m5C) modification in different tRNAs, namely DNMT2 and NSUN6, an ultra-large commercially available chemical space was virtually screened by physicochemical property filtering, molecular docking, and clustering to identify new ligands for those enzymes. Novel chemotypes binding to DNMT2 and NSUN6 with affinities down to KD,app = 37 µM and KD,app = 12 µ
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Zhou, Zehao, Huan-Qiu Li, and Feng Liu. "DNA Methyltransferase Inhibitors and their Therapeutic Potential." Current Topics in Medicinal Chemistry 18, no. 28 (2019): 2448–57. http://dx.doi.org/10.2174/1568026619666181120150122.

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Aberrant DNA methylation at the 5-position of cytosine, catalyzed by DNA methyltransferases (DNMTs), is associated with not only various cancers by silencing of tumor suppressor genes but also other diseases. The DNMTs, especially the DNMT1, DNMT3A and DNMT3B, are often overexpressed in various cancer tissues and cell lines. DNMTs are important epigenetic targets for drug development since the DNA methylation is reversible. This review summarizes an array of nucleoside and non-nucleoside inhibitors of DNMTs, as well as their biological activities. Among these inhibitors, the nucleoside analogu
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Dwivedi, Lalita, Aishwarya Jaiswal, Reenu Punia, et al. "Decursin Inhibits Expression and Nuclear Localization of DNMT and HDAC, and Suppresses the Growth and Survival of Prostate Cancer Cells." Asian Pacific Journal of Cancer Biology 9, no. 3 (2024): 271–81. http://dx.doi.org/10.31557/apjcb.2024.9.3.271-281.

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Background: DNA methyltransferases (DNMT) and histone deacetylases (HDAC) inhibitors have utility in cancer therapeutics. However, they are associated with toxicity, which limits their efficacy against carcinomas. Previously, we reported that decursin has anticancer activity against prostate cancer (PCa). In this study, we investigated its epigenetic role in inhibiting the survival of PCa cells. Methods and Results: PCa cell viability was evaluated using MTT and trypan blue assays. The effect of decursin on global methylation and gene-specific methylation was assessed by dot blot assay and MS-
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Zhang, Jiayu, Cheng Yang, Chunfu Wu, Wei Cui, and Lihui Wang. "DNA Methyltransferases in Cancer: Biology, Paradox, Aberrations, and Targeted Therapy." Cancers 12, no. 8 (2020): 2123. http://dx.doi.org/10.3390/cancers12082123.

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DNA methyltransferases are an essential class of modifiers in epigenetics. In mammals, DNMT1, DNMT3A and DNMT3B participate in DNA methylation to regulate normal biological functions, such as embryo development, cell differentiation and gene transcription. Aberrant functions of DNMTs are frequently associated with tumorigenesis. DNMT aberrations usually affect tumor-related factors, such as hypermethylated suppressor genes and genomic instability, which increase the malignancy of tumors, worsen the prognosis for patients, and greatly increase the difficulty of cancer therapy. However, the impa
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Ito, Takamasa, Musashi Kubiura-Ichimaru, Yuri Murakami, et al. "DNMT1 regulates the timing of DNA methylation by DNMT3 in an enzymatic activity-dependent manner in mouse embryonic stem cells." PLOS ONE 17, no. 1 (2022): e0262277. http://dx.doi.org/10.1371/journal.pone.0262277.

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DNA methylation (DNAme; 5-methylcytosine, 5mC) plays an essential role in mammalian development, and the 5mC profile is regulated by a balance of opposing enzymatic activities: DNA methyltransferases (DNMTs) and Ten-eleven translocation dioxygenases (TETs). In mouse embryonic stem cells (ESCs), de novo DNAme by DNMT3 family enzymes, demethylation by the TET-mediated conversion of 5mC to 5-hydroxymethylation (5hmC), and maintenance of the remaining DNAme by DNMT1 are actively repeated throughout cell cycles, dynamically forming a constant 5mC profile. Nevertheless, the detailed mechanism and ph
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Mohan, K. Naga. "Stem Cell Models to Investigate the Role of DNA Methylation Machinery in Development of Neuropsychiatric Disorders." Stem Cells International 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/4379425.

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Epigenetic mechanisms underlie differentiation of pluripotent stem cells into different lineages that contain identical genomes but express different sets of cell type-specific genes. Because of high discordance rates in monozygotic twins, epigenetic mechanisms are also implicated in development of neuropsychiatric disorders such as schizophrenia and autism. In support of this notion, increased levels of DNA methyltransferases (DNMTs), DNMT polymorphisms, and dysregulation of DNA methylation network were reported among schizophrenia patients. These results point to the importance of developmen
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Park, Joo-Hoo, Jae-Min Shin, Hyun-Woo Yang та Il-Ho Park. "DNMTs Are Involved in TGF-β1-Induced Epithelial–Mesenchymal Transitions in Airway Epithelial Cells". International Journal of Molecular Sciences 23, № 6 (2022): 3003. http://dx.doi.org/10.3390/ijms23063003.

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Chronic rhinosinusitis (CRS) pathogenesis is closely related to tissue remodeling, including epithelial–mesenchymal transition (EMT). Epigenetic mechanisms play key roles in EMT. DNA methylation, mediated by DNA methyltransferases (DNMTs), is an epigenetic marker that is critical to EMT. The goal of this study was to determine whether DNMTs were involved in TGF-β1-induced EMT and elucidate the underlying mechanisms in nasal epithelial cells and air–liquid interface cultures. Global DNA methylation and DNMT activity were quantified. DNMT expression was measured using real-time PCR (qRT–PCR) in
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Kunert, N. "A Dnmt2-like protein mediates DNA methylation in Drosophila." Development 130, no. 21 (2003): 5083–90. http://dx.doi.org/10.1242/dev.00716.

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Kiani, Jafar, Valérie Grandjean, Reinhard Liebers, et al. "RNA–Mediated Epigenetic Heredity Requires the Cytosine Methyltransferase Dnmt2." PLoS Genetics 9, no. 5 (2013): e1003498. http://dx.doi.org/10.1371/journal.pgen.1003498.

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Li, Sisi, Jiamu Du, Hui Yang, Juan Yin, Jianping Ding, and Jiang Zhong. "Functional and structural characterization of DNMT2 from Spodoptera frugiperda." Journal of Molecular Cell Biology 5, no. 1 (2012): 64–66. http://dx.doi.org/10.1093/jmcb/mjs057.

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Li, Huari, Huiru Liu, Daiyun Zhu, et al. "Biological function molecular pathways and druggability of DNMT2/TRDMT1." Pharmacological Research 205 (July 2024): 107222. http://dx.doi.org/10.1016/j.phrs.2024.107222.

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Mohammadzadeh, Nooshin, Fatemeh Mosaffa, Ehsan Khadivi, Rosa Jahangiri, and Khadijeh Jamialahmadi. "Increased Expression of DNA Methyltransferase 1 and 3B Correlates with Tumor Grade in Laryngeal Squamous Cell Carcinoma." Pharmaceutical Sciences 27, no. 3 (2020): 393–98. http://dx.doi.org/10.34172/ps.2020.86.

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Background: DNA methyltransferase (DNMT) enzymes, encoded by DNMT1, DNMT3A andDNMT3B genes, play a major role in the development of cancers through aberrant promotermethylation. Due to little information about the biological and clinical significance of expressionchanges of these genes in Laryngeal Squamous Cell carcinoma (LSCC), the current study wasdesigned to evaluate the contribution of DNMTs expression as potential diagnostic biomarkersin progression of LSCC. Methods: DNMT1, DNMT3A and DNMT3B expressions in tumoral and normal tissues fromthirty-three LSCC patients were evaluated by relati
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Nada, Alaa H., Hoda Mahrous, and Ahmed I. Abd Elmaksoud. "Molecular Insights into the Anticancer Mechanism of Glycyrrhetinic Acid in Hepatocellular Carcinoma." Scholars International Journal of Biochemistry 7, no. 02 (2024): 16–24. http://dx.doi.org/10.36348/sijb.2024.v07i02.001.

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The study aimed to predict the binding affinity and interaction patterns between DNMT1, DNMT2, DNMT3A, DNMT3B, TET-1, c-Myc, TET-2, NF-kB and methionine synthase in complex with Glycyrrhetinic acid (GA) using molecular docking simulations. In this study, A crystal structure of proteins (DNA methyltransferase 1, DNA methyltransferase 2, DNA methyltransferase 3A, DNA methyltransferase 3B, NF-kB, TET-1, c-Myc, TET-2 and methionine synthetase) was downloaded from the Protein Data Bank (PDB). the Auto Dock Vina and visualization by Discovery Studio and Chimera program were utilized for molecular do
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Maugeri, Andrea, Martina Barchitta, Maria Mazzone, Francesco Giuliano, Guido Basile, and Antonella Agodi. "Resveratrol Modulates SIRT1 and DNMT Functions and Restores LINE-1 Methylation Levels in ARPE-19 Cells under Oxidative Stress and Inflammation." International Journal of Molecular Sciences 19, no. 7 (2018): 2118. http://dx.doi.org/10.3390/ijms19072118.

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The role of epigenetic alterations in the pathogenesis of retinal degenerative diseases, including age-related macular degeneration (AMD), has been pending so far. Our study investigated the effect of oxidative stress and inflammation on DNA methyltransferases (DNMTs) and Sirtuin 1 (SIRT1) functions, as well as on long interspersed nuclear element-1 (LINE-1) methylation, in human retinal pigment epithelial (ARPE-19) cells. Therefore, we evaluated whether treatment with resveratrol may modulate DNMT and SIRT1 functions and restore changes in LINE-1 methylation. Cells were treated with 25 mU/mL
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Kim, Dae Joong. "The Role of the DNA Methyltransferase Family and the Therapeutic Potential of DNMT Inhibitors in Tumor Treatment." Current Oncology 32, no. 2 (2025): 88. https://doi.org/10.3390/curroncol32020088.

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Members of the DNA methyltransferase (DNMT) family have been recognized as major epigenetic regulators of altered gene expression during tumor development. They establish and maintain DNA methylation of the CpG island of promoter and non-CpG region of the genome. The abnormal methylation status of tumor suppressor genes (TSGs) has been associated with tumorigenesis, leading to genomic instability, improper gene silence, and immune evasion. DNMT1 helps preserve methylation patterns during DNA replication, whereas the DNMT3 family is responsible for de novo methylation, creating new methylation
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Zwergel, Clemens, Rossella Fioravanti, Giulia Stazi, et al. "Novel Quinoline Compounds Active in Cancer Cells through Coupled DNA Methyltransferase Inhibition and Degradation." Cancers 12, no. 2 (2020): 447. http://dx.doi.org/10.3390/cancers12020447.

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DNA methyltransferases (DNMTs) play a relevant role in epigenetic control of cancer cell survival and proliferation. Since only two DNMT inhibitors (azacitidine and decitabine) have been approved to date for the treatment of hematological malignancies, the development of novel potent and specific inhibitors is urgent. Here we describe the design, synthesis, and biological evaluation of a new series of compounds acting at the same time as DNMTs (mainly DNMT3A) inhibitors and degraders. Tested against leukemic and solid cancer cell lines, 2a–c and 4a–c (the last only for leukemias) displayed up
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Heil, Caiti S. Smukowski. "No Detectable Effect of the DNA Methyltransferase DNMT2 onDrosophilaMeiotic Recombination." G3: Genes|Genomes|Genetics 4, no. 11 (2014): 2095–100. http://dx.doi.org/10.1534/g3.114.012393.

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Jeltsch, Albert, Ann Ehrenhofer-Murray, Tomasz P. Jurkowski, et al. "Mechanism and biological role of Dnmt2 in Nucleic Acid Methylation." RNA Biology 14, no. 9 (2016): 1108–23. http://dx.doi.org/10.1080/15476286.2016.1191737.

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Ehrenhofer-Murray, Ann. "Cross-Talk between Dnmt2-Dependent tRNA Methylation and Queuosine Modification." Biomolecules 7, no. 4 (2017): 14. http://dx.doi.org/10.3390/biom7010014.

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Hermann, Andrea, Sigrid Schmitt, and Albert Jeltsch. "The Human Dnmt2 Has Residual DNA-(Cytosine-C5) Methyltransferase Activity." Journal of Biological Chemistry 278, no. 34 (2003): 31717–21. http://dx.doi.org/10.1074/jbc.m305448200.

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Ашапкин, В. В., Л. И. Кутуева та Б. Ф. Ванюшин. "Dnmt2 – самая эволюционно консервативная и загадочная цитозиновая ДНК-метилтрансфераза эукариот". Генетика 52, № 3 (2016): 269–82. http://dx.doi.org/10.7868/s0016675816030024.

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