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https://www.readbyqxmd.com/read/28098901/effect-of-evodiamine-and-berberine-on-the-interaction-between-dnmts-and-target-micrornas-during-malignant-transformation-of-the-colon-by-tgf-%C3%AE-1
#1
Chao Huang, Hong Liu, Xiu-Li Gong, Li-Yun Wu, Bin Wen
The tissue microenvironment functions as a crucial player in carcinogenesis, and transforming growth factor-β1 (TGF-β1) within the microenvironment stimulates the formation of neoplasms. Using an in vitro model of malignancy induced by TGF-β1, we assessed the effect of evodiamine and berberine on the interaction between DNA methyltransferases (DNMTs) and target microRNAs (miRNAs) in the model. Colon tissues from neonatal rats 7 days of age were cultured and malignancy was induced by TGF-β1 in vitro for 48 h, and then the tissues were respectively treated with evodiamine and berberine for 24 h...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28043331/avermectin-induced-global-dna-hypomethylation-and-over-expression-of-heat-shock-proteins-in-cardiac-tissues-of-pigeon
#2
Ci Liu, Ye Cao, Shuo Zhou, Pervez Ahmed Khoso, Shu Li
Despite increasing evidences pointing to residues of avermectin (AVM) pose toxic effects on non-target organisms in environment, but the data in pigeon is insufficient. The alteration of global DNA methylation and response of heat shock proteins (Hsps) are important for assessing the AVM toxicity in cardiac tissues of pigeon (Columba livia). To investigate the effects of AVM exposure in cardiac tissues of pigeon, we detected the expression levels of DNA methyltransferases (Dnmts), methylated DNA-binding domain protein 2 (MBD2), and Hsp 60, 70 and 90...
January 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/27989104/dna-demethylation-of-the-foxp3-enhancer-is-maintained-through-modulation-of-ten-eleven-translocation-and-dna-methyltransferases
#3
Varun Sasidharan Nair, Mi Hye Song, Myunggon Ko, Kwon Ik Oh
Stable expression of Foxp3 is ensured by demethylation of CpG motifs in the Foxp3 intronic element, the conserved non-coding sequence 2 (CNS2), which persists throughout the lifespan of regulatory T cells (Tregs). However, little is known about the mechanisms on how CNS2 demethylation is sustained. In this study, we found that Ten-Eleven-Translocation (Tet) DNA dioxygenase protects the CpG motifs of CNS2 from re-methylation by DNA methyltransferases (Dnmts) and prevents Tregs from losing Foxp3 expression under inflammatory conditions...
December 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27981510/aberrant-cpg-methylation-mediates-abnormal-transcription-of-mao-a-induced-by-acute-and-chronic-l-3-4-dihydroxyphenylalanine-administration-in-sh-sy5y-neuronal-cells
#4
Zhaofei Yang, Xuan Wang, Jian Yang, Min Sun, Yong Wang, Xiaomin Wang
L-3,4-dihydroxyphenylalanine (L-dopa) remains the most effective drug for therapy of Parkinson's disease (PD); however, long-term use of it causes serious side effects. L-dopa-induced dyskinesia (LID) has consistently been related to L-dopa-derived excessive dopamine release, but the mechanisms have not been addressed very clear. Monoamine oxidase A (MAO-A) is one of the key enzymes in dopamine metabolism and therefore may be involved in L-dopa-induced side effects. And, epigenetic modification controls MAO-A gene transcription...
December 15, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27934997/lead-pb-exposure-reduces-global-dna-methylation-level-by-non-competitive-inhibition-and-alteration-of-dnmt-expression
#5
Oscar F Sanchez, Jinyoung Lee, Nathaphon Yu King Hing, Seong-Eun Kim, Jennifer L Freeman, Chongli Yuan
Low-dose exposure to lead (Pb) is connected to developmental neurological alterations by inducing molecular changes, such as aberrant gene expression patterns. The attributing molecular mechanism, however, is not well-elucidated. In this study, we revealed epigenetic features and mechanisms that can alter gene expression patterns by identifying changes in DNA methyltransferase (DNMT) activity, expression pattern and DNA methylation level using moelcular studies and a zebrafish animal model. We characterized the effects of Pb on the activities of various DNMTs in vitro and determined the molecular role of Pb in modulating DNMT activity via kinetic experiments...
December 9, 2016: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/27916575/circannual-and-circadian-rhythms-of-hypothalamic-dna-methyltransferase-and-histone-deacetylase-expression-in-male-siberian-hamsters-phodopus-sungorus
#6
Tyler J Stevenson
Precise timing of gene transcription is a fundamental component of many biological rhythms. DNA methylation and histone acetylation are two epigenetic modifications that can affect the probability of gene transcription and RNA expression. Enzymes involved in DNA methylation (dnmts) have been shown to exhibit photoperiodic rhythms in expression in the hypothalamus, which coincide with hypothalamic expression of deiodinase type III (dio3), a gene involved in the photoperiodic regulation of reproduction. It is currently unknown whether enzymes involved in histone deacetylation (hdacs) also vary in response to photoperiod, nor have seasonal changes in the circadian waveforms of methylation and/or acetylation enzymes been examined...
December 1, 2016: General and Comparative Endocrinology
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
#7
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
#8
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
#9
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...
January 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27884978/oestrogen-receptor-negativity-in-breast-cancer-a-cause-or-consequence
#10
REVIEW
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 oestrogen receptor α (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 oestrogen receptor (ER) negativity and endocrine resistance in breast cancer is questionable...
December 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
#11
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
#12
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
#13
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
#14
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...
January 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27846368/epigenetic-therapy-approaches-in-non-small-cell-lung-cancer-update-and-perspectives
#15
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...
December 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
#16
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
#17
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
#18
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
#19
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
#20
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
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