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https://www.readbyqxmd.com/read/27910778/mirsnps-of-mir1274-and-mir3202-genes-that-target-mecp2-and-dnmt3b-are-associated-with-lung-cancer-risk-a-study-conducted-on-massarray-genotyping
#1
Cansu Ozbayer, Irfan Degirmenci, Derya Ustuner, Guntulu Ak, Faruk Saydam, Ertugrul Colak, Hasan Veysi Gunes, Muzaffer Metintas
Genetic variants of miRNAs that target DNMTs and MBDs involved in DNA methylation were scanned with current databases, and 35 miRSNPs in 22 miRNA genes were identified. The aim of the study was to determine the association between these variants of miRNA genes and lung cancer (LC). DNA samples were isolated from blood samples and genotyped using a Sequenom MassARRAY System. An association between the rs188912830 gene variant of miR3202 that targets the MeCP2 protein and LC was indicated in both subtypes. The presence of the C-allele in patients with LC and its subtypes was significantly lower, and the absence of the C-allele was determined to increase the risk of LC by 7,429-times compared to the presence (p=0,010)...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27900031/chromosome-16q-genes-cdh1-cdh13-and-adamts18-are-correlated-and-frequently-methylated-in-human-lymphoma
#2
Lobna Alkebsi, Hiroshi Handa, Akihiko Yokohama, Takayuki Saitoh, Norifumi Tsukamoto, Hirokazu Murakami
The products of the E-cadherin (CDH1), H-cadherin (CDH13) and a disintegrin and metalloproteinase with thrombospondin motif 18 (ADAMTS18) genes are proteins displaying structural features and functions on the cell surface membrane, and have been reported to be involved in cancer progression. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and methylation-specific PCR (MSP) analysis, the promoter methylation status and messenger RNA (mRNA) expression levels of CDH1, CDH13 and ADAMTS18, which are putative tumor-suppressor genes located on chromosome 16q, were evaluated...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899265/discovery-of-novel-dna-methyltransferase-3a-inhibitors-via-structure-based-virtual-screening-and-biological-assays
#3
Zhiyuan Shao, Pan Xu, Wen Xu, Linjuan Li, Shien Liu, Rukang Zhang, Yu-Chih Liu, Chenhua Zhang, Shijie Chen, Cheng Luo
DNA methyltransferases are involved in diverse biological processes and abnormal methylation patterns play essential roles in cancer initiation and progression. DNA methyltransferase 3A (DNMT3A) acting as a de novo DNA methyltransferase, has gained widespread attention especially in haematological diseases. To date, large numbers of DNMTs inhibitors have been discovered, however, the small molecular inhibitors targeting DNMT3A are still in its infancy. In this study, structure-based virtual screening in combination with biological assays was performed to discovery potent novel DNMT3A inhibitors...
November 11, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27884978/estrogen-receptor-negativity-in-breast-cancer-a-cause-or-consequence
#4
Vijaya Narasihma Reddy Gajulapalli, Vijaya Lakshmi Malisetty, Suresh Kumar Chitta, Bramanandam Manavathi
Endocrine resistance, which occurs either by de novo or acquired route, is posing a major challenge in treating hormone-dependent breast cancers by endocrine therapies. The loss of ERα expression is the vital cause of establishing endocrine resistance in this subtype. Understanding the mechanisms that determine the causes of this phenomenon are therefore essential to reduce the disease efficacy. But how we negate estrogen receptor (ER) negativity and endocrine resistance in breast cancer is questionable, to answer that two important approaches are considered: 1) Understanding the cellular origin of heterogeneity and ER negativity in breast cancers, and 2) characterization of molecular regulators of endocrine resistance...
November 24, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27865785/dnmt1-dnmt3a-and-dnmt3b-cooperate-in-photoreceptor-and-outer-plexiform-layer-development-in-the-mammalian-retina
#5
Ratnesh K Singh, Ramya K Mallela, Abigail Hayes, Nicholas R Dunham, Morgan E Hedden, Raymond A Enke, Robert N Fariss, Hal Sternberg, Michael D West, Igor O Nasonkin
Characterizing the role of epigenetic regulation in the mammalian retina is critical for understanding fundamental mechanisms of retinal development and disease. DNA methylation, an epigenetic modifier of genomic DNA, plays an important role in modulating networks of tissue and cell-specific gene expression. However, the impact of DNA methylation during retinal development and homeostasis of retinal neurons remains unclear. Here, we have created a tissue-specific DNA methyltransferase (Dnmt) triple mutant mouse in an effort to characterize the impact of DNA methylation in retinal development and homeostasis...
November 16, 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/27857218/tet1-dependent-epigenetic-modification-of-bdnf-expression-in-dorsal-horn-neurons-mediates-neuropathic-pain-in-rats
#6
Ming-Chun Hsieh, Cheng-Yuan Lai, Yu-Cheng Ho, Hsueh-Hsiao Wang, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
Ten-eleven translocation methylcytosine dioxygenase 1 (Tet1) mediates the conversion of 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC), hence promoting DNA demethylation. Although recent studies have linked the DNA demethylation of specific genes to pain hypersensitivity, the role of spinal Tet1-dependent DNA demethylation in nociception hypersensitivity development remains elusive. Here, we report correlated with behavioral allodynia, spinal nerve ligation (SNL) upregulated Tet1 expression in dorsal horn neurons that hydroxylate 5 mC to 5 hmC at CpG dinucleotides in the bdnf promoter to promote spinal BDNF expression at day 7 after operation...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27855348/role-of-dna-methylation-in-bisphenol-a-exposed-mouse-spermatocyte
#7
Li Yin, Yanlin Dai, Xiao Jiang, Yong Liu, Hongqiang Chen, Fei Han, Jia Cao, Jinyi Liu
As a widespread environmental contaminant, bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) has been implicated in male reproductive function injury. Previous studies have investigated the mechanisms of DNA damage and oxidative stress caused by BPA; however, little is known regarding its impact on DNA methylation. In this paper, we assessed the adverse effects of BPA on mouse spermatocytes and investigated a potential role of DNA methylation. We demonstrated that BPA exposure inhibited cell proliferation, reduced the DNA replication capacity, and triggered apoptosis in GC-2 cells...
December 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/27852009/treatment-of-cardiovascular-pathology-with-epigenetically-active-agents-focus-on-natural-and-synthetic-inhibitors-of-dna-methylation-and-histone-deacetylation
#8
REVIEW
Dimitry A Chistiakov, Alexander N Orekhov, Yuri V Bobryshev
Cardiovascular disease (CVD) retains a leadership as a major cause of human death worldwide. Although a substantial progress was attained in the development of cardioprotective and vasculoprotective drugs, a search for new efficient therapeutic strategies and promising targets is under way. Modulation of epigenetic CVD mechanisms through administration epigenetically active agents is one of such new approaches. Epigenetic mechanisms involve heritable changes in gene expression that are not linked to the alteration of DNA sequence...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27846368/epigenetic-therapy-approaches-in-non-small-cell-lung-cancer-update-and-perspectives
#9
Insa Schiffmann, Gabriele Greve, Manfred Jung, Michael Lübbert
Non-small cell lung cancer (NSCLC) still constitutes the most common cancer-related cause of death worldwide. All efforts to introduce suitable treatment options using chemotherapeutics or targeted therapies have, up to this point, failed to exhibit a substantial effect on the 5-year-survival rate. The involvement of epigenetic alterations in the evolution of different cancers has led to the development of epigenetics-based therapies, mainly targeting DNA methyltransferases (DNMTs) and histone-modifying enzymes...
November 15, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27843576/micrornas-interfere-with-dna-methylation-in-rheumatoid-arthritis-synovial-fibroblasts
#10
Niharika Gaur, Emmanuel Karouzakis, Selene Glück, Edvardas Bagdonas, Astrid Jüngel, Beat A Michel, Renate E Gay, Steffen Gay, Mojca Frank-Bertoncelj, Michel Neidhart
BACKGROUND: The DNA of rheumatoid arthritis synovial fibroblasts (RASF) is globally hypomethylated; this contributes to an aggressive behaviour. In an attempt to remethylate these cells, we supplemented with methyl donors. We investigated the possible interference of microRNAs (miRs). MATERIAL AND METHODS: RASF were treated with L-methionine or betaine. Transcripts of de novo methyltransferases (DNMTs) and miRs were measured by real-time PCR, and a transcription PCR array was performed...
2016: RMD Open
https://www.readbyqxmd.com/read/27826849/engineering-and-directed-evolution-of-dna-methyltransferases
#11
Paola Laurino, Liat Rockah-Shmuel, Dan S Tawfik
DNA methyltransferases (MTases) constitute an attractive target for protein engineering, thus opening the road to new ways of manipulating DNA in a unique and selective manner. Here, we review various aspects of MTase engineering, both methodological and conceptual, and also discuss future directions and challenges. Bacterial MTases that are part of restriction/modification (R/M) systems offer a convenient way for the selection of large gene libraries, both in vivo and in vitro. We review these selection methods, their strengths and weaknesses, and also the prospects for new selection approaches that will enable the directed evolution of mammalian DNA methyltransferases (Dnmts)...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27826847/dna-methyltransferase-inhibitors-development-and-applications
#12
Marie Lopez, Ludovic Halby, Paola B Arimondo
As described in previous chapters of this book, DNA methylation is involved in numerous biological processes, and modulation of the activity of DNA methyltransferases (DNMTs) is a powerful strategy to modulate, restore, or reduce DNA methylation. In this chapter, we will present examples of inhibitors of DNMTs (DNMTi) and review the fields of applications of DNMTi mainly as therapeutic molecules, for example, in cancers, cardiovascular or neurological diseases, but also as bioengineering tools. Finally, the limits of currently available inhibitors will be discussed and the perspectives to discover improved DNMTi will be presented...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27826837/genetic-studies-on-mammalian-dna-methyltransferases
#13
Jiameng Dan, Taiping Chen
Cytosine methylation at the C5-position, generating 5-methylcytosine (5mC), is a DNA modification found in many eukaryotic organisms, including fungi, plants, invertebrates, and vertebrates, albeit its levels vary greatly in different organisms. In mammals, cytosine methylation occurs predominantly in the context of CpG dinucleotides, with the majority (60-80 %) of CpG sites in their genomes being methylated. DNA methylation plays crucial roles in the regulation of chromatin structure and gene expression and is essential for mammalian development...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27826836/enzymology-of-mammalian-dna-methyltransferases
#14
Renata Z Jurkowska, Albert Jeltsch
DNA methylation is currently one of the hottest topics in basic and biomedical research. Despite tremendous progress in understanding the structures and biochemical properties of the mammalian DNA nucleotide methyltransferases (DNMTs), principles of their regulation in cells have only begun to be uncovered. In mammals, DNA methylation is introduced by the DNMT1, DNMT3A, and DNMT3B enzymes, which are all large multi-domain proteins. These enzymes contain a catalytic C-terminal domain with a characteristic cytosine-C5 methyltransferase fold and an N-terminal part with different domains that interacts with other proteins and chromatin and is involved in targeting and regulation of the DNMTs...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27826835/domain-structure-of-the-dnmt1-dnmt3a-and-dnmt3b-dna-methyltransferases
#15
Shoji Tajima, Isao Suetake, Kohei Takeshita, Atsushi Nakagawa, Hironobu Kimura
In mammals, three DNA methyltransferases, Dnmt1, Dnmt3a, and Dnmt3b, have been identified. Dnmt3a and Dnmt3b are responsible for establishing DNA methylation patterns produced through their de novo-type DNA methylation activity in implantation stage embryos and during germ cell differentiation. Dnmt3-like (Dnmt3l), which is a member of the Dnmt3 family but does not possess DNA methylation activity, was reported to be indispensable for global methylation in germ cells. Once the DNA methylation patterns are established, maintenance-type DNA methyltransferase Dnmt1 faithfully propagates them to the next generation via replication...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27826104/in-vivo-and-in-silico-studies-to-identify-mechanisms-associated-with-nurr1-modulation-following-early-life-exposure-to-permethrin-in-rats
#16
Donatella Fedeli, Maura Montani, Laura Bordoni, Roberta Galeazzi, Cinzia Nasuti, Luísa Correia-Sá, Valentina F Domingues, Maini Jayant, Vani Brahmachari, Luca Massaccesi, Emiliano Laudadio, Rosita Gabbianelli
The present work was designed to study the mechanisms associated with Nurr1 modulation following early life permethrin (PERM) treatment during rat's life span. Here we demonstrate that PERM exposure in rats, at a dose close to No Observed Adverse Effect Level (NOAEL) for 15days during neonatal brain development leads to its accumulation long after exposure. In striatum from adolescent rats we detected an increase in DNA methyltransferases (DNMTs) such as DNMT1, DNMT3a, Tyrosine hydroxylase, monomeric and aggregated α-synuclein protein levels...
November 5, 2016: Neuroscience
https://www.readbyqxmd.com/read/27818231/epigenetic-reactivation-of-rassf1a-by-phenethyl-isothiocyanate-peitc-and-promotion-of-apoptosis-in-lncap-cells
#17
Sarandeep S S Boyanapalli, Wenji Li, Francisco Fuentes, Yue Guo, Christina N Ramirez, Ximena-Parades Gonzalez, Douglas Pung, Ah-Ng Tony Kong
Epigenetic silencing of tumor suppressor genes is a phenomenon frequently observed in multiple cancers. Ras-association domain family 1 isoform A (RASSF1A) is a well-characterized tumor suppressor that belongs to the Ras-association domain family. Several studies have demonstrated that hypermethylation of the RASSF1A promoter is frequently observed in lung, prostate, and breast cancers. Phenethyl isothiocyanate (PEITC), a phytochemical abundant in cruciferous vegetables, possesses chemopreventive activities; however, its potential involvement in epigenetic mechanisms remains elusive...
November 3, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27789275/dnmt1-dnmt3a-and-dnmt3b-polymorphisms-associated-with-gastric-cancer-risk-a-systematic-review-and-meta-analysis
#18
Hongjia Li, Wen Li, Shanshan Liu, Shaoqi Zong, Weibing Wang, Jianlin Ren, Qi Li, Fenggang Hou, Qi Shi
BACKGROUND: Increasing studies showed that abnormal changes in single nucleotide polymorphisms (SNPs) of DNMTs (DNMT1, DNMT3A and DNMT3B) were associated with occurrence or decrease of various tumors. However, the associations between DNMTs variations and gastric cancer (GC) risk were still conflicting. We aimed to assess the effect of DNMTs polymorphisms on the susceptibility to GC. METHODS: Firstly, we did a meta-analysis for 7 SNPs (rs16999593, rs2228611, rs8101866 in DNMT1, rs1550117, rs13420827 in DNMT3A, rs1569686, rs2424913 in DNMT3B)...
October 19, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27786595/cocaine-mediated-downregulation-of-microglial-mir-124-expression-involves-promoter-dna-methylation
#19
Ming-Lei Guo, Palsamy Periyasamy, Ke Liao, Yeon Hee Kook, Fang Niu, Shannon E Callen, Shilpa Buch
Neuroinflammation plays a critical role in the development of reward-related behavior in cocaine self-administration rodents. Cocaine, one of most commonly abused drugs, has been shown to activate microglia both in vitro and in vivo. Detailed molecular mechanisms underlying cocaine-mediated microglial activation remain poorly understood. microRNAs (miRs), belonging to a class of small noncoding RNA superfamily have been shown to modulate the activation status of microglia. miR-124, one of the microglia-enriched miRs, functions as an anti-inflammatory regulator that maintains microglia in a quiescent state...
October 27, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27780634/an-oligodeoxyribonucleotide-containing-5-formyl-2-deoxycytidine-fc-at-the-cpg-site-forms-a-covalent-complex-with-dna-cytosine-5-methyltransferases-dnmts
#20
Kousuke Sato, Kyoji Kawamoto, Shintaro Shimamura, Satoshi Ichikawa, Akira Matsuda
5-Methylcytosine (mC) is known to induce epigenetic changes. Ten-eleven translocation (TET) enzymes produce the further oxidized 5-substituted cytosine derivatives, 5-formylcytosine (fC) and 5-carboxylcytosine (caC). However, their roles are unclear thus far. Here, we synthesized oligodeoxyribonucleotides (ODNs) containing 5-formyl-2'-deoxycytidine and examined their interactions with DNA cytosine-5 methyltransferase (DNMT). We found that the ODN sequence containing fCpG formed a covalent complex with both bacterial and mouse recombinant DNMTs in the absence of any cofactors...
October 14, 2016: Bioorganic & Medicinal Chemistry Letters
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