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https://www.readbyqxmd.com/read/27826836/enzymology-of-mammalian-dna-methyltransferases
#1
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
#2
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/27774769/developmental-dna-methyltransferase-expression-in-the-fire-ant-solenopsis-invicta
#3
Sasha Kay, Daniel Skowronski, Brendan G Hunt
DNA methylation is accomplished in animals by two classes of enzymes known as DNA methyltransferases, DNMT3 and DNMT1, which perform de novo methylation and maintenance methylation, respectively. Several studies of hymenopteran eusocial insects suggest that DNA methylation is capable of influencing developmental plasticity. However, fundamental questions remain about the patterning of DNA methylation during the course of insect development. In this study, we performed quantitative real-time PCR (qPCR) on transcripts from the single-copy orthologs of DNMT1 and DNMT3 in the red imported fire ant, Solenopsis invicta...
October 24, 2016: Insect Science
https://www.readbyqxmd.com/read/27748882/downregulation-of-dnmt3a-expression-increases-mir-182-induced-apoptosis-of-ovarian-cancer-through-caspase-3%C3%A2-and%C3%A2-caspase-9-mediated-apoptosis-and-dna-damage-response
#4
Wei Lu, Tanmin Lu, Xin Wei
In the present study, DNA (cytosine-5)-methyltransferase 3α (DNMT3a) is explored as an anticancer molecule in ovarian cancer treatment, and also the mechanistic link between DNMT3a and its regulatory signaling pathway in Caov-3 cells is provided. Firstly, DNMT3a protein expression in 12 freshly resected ovarian cancer patient tissues and tisssues from 8 ovariectomized patients was assessed. In the ovarian cancer tissues, DNMT3a expression was upregulated and miR-182 expression was downregulated. DNMT3a overexpression inhibited miR-182 expression and caspase-3 and -9 activity and suppressed p53 and c-Myc protein expression in Caov-3 cells...
September 28, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27731414/dna-methyltransferases-and-stress-related-genes-expression-in-zebrafish-larvae-after-exposure-to-heat-and-copper-during-reprogramming-of-dna-methylation
#5
Jennifer Dorts, Elodie Falisse, Emilie Schoofs, Enora Flamion, Patrick Kestemont, Frédéric Silvestre
DNA methylation, a well-studied epigenetic mark, is important for gene regulation in adulthood and for development. Using genetic and epigenetic approaches, the present study aimed at evaluating the effects of heat stress and copper exposure during zebrafish early embryogenesis when patterns of DNA methylation are being established, a process called reprogramming. Embryos were exposed to 325 μg Cu/L from fertilization (<1 h post fertilization - hpf) to 4 hpf at either 26.5 °C or 34 °C, followed by incubation in clean water at 26...
October 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27521372/allosteric-control-of-mammalian-dna-methyltransferases-a-new-regulatory-paradigm
#6
Albert Jeltsch, Renata Z Jurkowska
In mammals, DNA methylation is introduced by the DNMT1, DNMT3A and DNMT3B methyltransferases, which are all large multi-domain proteins containing a catalytic C-terminal domain and an N-terminal part with regulatory functions. Recently, two novel regulatory principles of DNMTs were uncovered. It was shown that their catalytic activity is under allosteric control of N-terminal domains with autoinhibitory function, the RFT and CXXC domains in DNMT1 and the ADD domain in DNMT3. Moreover, targeting and activity of DNMTs were found to be regulated in a concerted manner by interactors and posttranslational modifications (PTMs)...
October 14, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27281847/-dnmt2-is-the-most-evolutionary-conserved-and-enigmatic-cytosine-dna-methyltransferase-in-eukaryotes
#7
REVIEW
V V Ashapkin, L I Kutueva, B F Vanyushin
Dnmt2 is the most strongly conserved cytosine DNA methyltransferase in eukaryotes. It has been found in all organisms possessing methyltransferases of the Dnmt1 and Dnmt3 families, whereas in many others Dnmt2 is the sole cytosine DNA methyltransferase. The Dnmt2 molecule contains all conserved motifs of cytosine DNA methyltransferases. It forms 3D complexes with DNA very similar to those of bacterial DNA methyltransferases and performs cytosine methylation by a catalytic mechanism common to all cytosine DNA methyltransferases...
March 2016: Genetika
https://www.readbyqxmd.com/read/27179026/an-epigenetic-switch-regulates-de-novo-dna-methylation-at-a-subset-of-pluripotency-gene-enhancers-during-embryonic-stem-cell-differentiation
#8
Christopher J Petell, Lama Alabdi, Ming He, Phillip San Miguel, Richard Rose, Humaira Gowher
Coordinated regulation of gene expression that involves activation of lineage specific genes and repression of pluripotency genes drives differentiation of embryonic stem cells (ESC). For complete repression of pluripotency genes during ESC differentiation, chromatin at their enhancers is silenced by the activity of the Lsd1-Mi2/NuRD complex. The mechanism/s that regulate DNA methylation at these enhancers are largely unknown. Here, we investigated the affect of the Lsd1-Mi2/NuRD complex on the dynamic regulatory switch that induces the local interaction of histone tails with the Dnmt3 ATRX-DNMT3-DNMT3L (ADD) domain, thus promoting DNA methylation at the enhancers of a subset of pluripotency genes...
September 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27098563/dna-methylation-and-targeted-sequencing-of-methyltransferases-family-genes-in-canine-acute-myeloid-leukaemia-modelling-human-myeloid-leukaemia
#9
I Bronzini, L Aresu, M Paganin, L Marchioretto, S Comazzi, F Cian, F Riondato, L Marconato, V Martini, G Te Kronnie
Tumours shows aberrant DNA methylation patterns, being hypermethylated or hypomethylated compared with normal tissues. In human acute myeloid leukaemia (hAML) mutations in DNA methyltransferase (DNMT3A) are associated to a more aggressive tumour behaviour. As AML is lethal in dogs, we defined global DNA methylation content, and screened the C-terminal domain of DNMT3 family of genes for sequence variants in 39 canine acute myeloid leukaemia (cAML) cases. A heterogeneous pattern of DNA methylation was found among cAML samples, with subsets of cases being hypermethylated or hypomethylated compared with healthy controls; four recurrent single nucleotide variations (SNVs) were found in DNMT3L gene...
April 21, 2016: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/26952936/epigenetic-response-to-environmental-stress-assembly-of-brg1-g9a-glp-dnmt3-repressive-chromatin-complex-on-myh6-promoter-in-pathologically-stressed-hearts
#10
Pei Han, Wei Li, Jin Yang, Ching Shang, Chiou-Hong Lin, Wei Cheng, Calvin T Hang, Hsiu-Ling Cheng, Chen-Hao Chen, Johnson Wong, Yiqin Xiong, Mingming Zhao, Stavros G Drakos, Andrea Ghetti, Dean Y Li, Daniel Bernstein, Huei-Sheng Vincent Chen, Thomas Quertermous, Ching-Pin Chang
Chromatin structure is determined by nucleosome positioning, histone modifications, and DNA methylation. How chromatin modifications are coordinately altered under pathological conditions remains elusive. Here we describe a stress-activated mechanism of concerted chromatin modification in the heart. In mice, pathological stress activates cardiomyocytes to express Brg1 (nucleosome-remodeling factor), G9a/Glp (histone methyltransferase), and Dnmt3 (DNA methyltransferase). Once activated, Brg1 recruits G9a and then Dnmt3 to sequentially assemble repressive chromatin-marked by H3K9 and CpG methylation-on a key molecular motor gene (Myh6), thereby silencing Myh6 and impairing cardiac contraction...
July 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26883339/gene-expression-differences-in-relation-to-age-and-social-environment-in-queen-and-worker-bumble-bees
#11
Gabrielle A Lockett, Edward J Almond, Timothy J Huggins, Joel D Parker, Andrew F G Bourke
Eusocial insects provide special insights into the genetic pathways influencing aging because of their long-lived queens and flexible aging schedules. Using qRT-PCR in the primitively eusocial bumble bee Bombus terrestris (Linnaeus), we investigated expression levels of four candidate genes associated with taxonomically widespread age-related pathways (coenzyme Q biosynthesis protein 7, COQ7; DNA methyltransferase 3, Dnmt3; foraging, for; and vitellogenin, vg). In Experiment 1, we tested how expression changes with queen relative age and productivity...
May 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/26859767/genome-transcriptome-and-methylome-sequencing-of-a-primitively-eusocial-wasp-reveal-a-greatly-reduced-dna-methylation-system-in-a-social-insect
#12
Daniel S Standage, Ali J Berens, Karl M Glastad, Andrew J Severin, Volker P Brendel, Amy L Toth
Comparative genomics of social insects has been intensely pursued in recent years with the goal of providing insights into the evolution of social behaviour and its underlying genomic and epigenomic basis. However, the comparative approach has been hampered by a paucity of data on some of the most informative social forms (e.g. incipiently and primitively social) and taxa (especially members of the wasp family Vespidae) for studying social evolution. Here, we provide a draft genome of the primitively eusocial model insect Polistes dominula, accompanied by analysis of caste-related transcriptome and methylome sequence data for adult queens and workers...
April 2016: Molecular Ecology
https://www.readbyqxmd.com/read/26823947/from-six-gene-polymorphisms-of-the-antioxidant-system-only-gpx-pro198leu-and-gstp1-ile105val-modulate-the-risk-of-acute-myeloid-leukemia
#13
Claudia Bănescu, Mihaela Iancu, Adrian P Trifa, Marcela Cândea, Erzsebet Benedek Lazar, Valeriu G Moldovan, Carmen Duicu, Florin Tripon, Andrei Crauciuc, Minodora Dobreanu
Oxidative stress might contribute to the occurrence of cancers, including the hematological ones. Various genetic polymorphisms were shown to increase the quantity of reactive oxygen species, a phenomenon that is able to induce mutations and thus promote cancers. The purpose of the study was to evaluate the association between CAT C262T, GPX1 Pro198Leu, MnSOD Ala16Val, GSTM1, GSTT1, and GSTP1 Ile105Val gene polymorphisms and acute myeloid leukemia risk, in a case-control study comprising 102 patients and 303 controls...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/26672019/dna-methylation-changes-induced-by-long-and-short-photoperiods-in-nasonia
#14
Mirko Pegoraro, Akanksha Bafna, Nathaniel J Davies, David M Shuker, Eran Tauber
Many organisms monitor the annual change in day length and use this information for the timing of their seasonal response. However, the molecular mechanisms underlying photoperiodic timing are largely unknown. The wasp Nasonia vitripennis is an emerging model organism that exhibits a strong photoperiodic response: Short autumnal days experienced by females lead to the induction of developmental arrest (diapause) in their progeny, allowing winter survival of the larvae. How female Nasonia control the developmental trajectory of their offspring is unclear...
February 2016: Genome Research
https://www.readbyqxmd.com/read/26596909/reading-between-the-lines-add-ing-histone-and-dna-methylation-marks-toward-a-new-epigenetic-sum
#15
Kyung-Min Noh, C David Allis, Haitao Li
Covalent modifications of both DNA and histones act in concert to define the landscape of our epigenome. In this review, we explore the interconnections between histone and DNA modifications by focusing on a conserved chromatin-binding regulatory domain, the ATRX-DNMT3-DNMT3L (ADD) domain. New studies show that the ADD domain is capable of sensing, and therefore integrating, the status of multiple histone modifications. This in turn dictates the in vivo localization or allosteric regulation of the full-length ADD-containing protein and its ability to function in downstream chromatin remodeling events...
March 18, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/26573388/a-regulatory-circuit-involving-mir-143-and-dnmt3a-mediates-vascular-smooth-muscle-cell-proliferation-induced-by-homocysteine
#16
Hui-Ping Zhang, Yan-Hua Wang, Cheng-Jian Cao, Xiao-Ming Yang, Sheng-Chao Ma, Xue-Bo Han, Xiao-Ling Yang, An-Ning Yang, Jue Tian, Hua Xu, Ming-Hao Zhang, Yi-Deng Jiang
Accumulating evidence has suggested that homocysteine (Hcy) is an independent risk factor for atherosclerosis (AS). Hcy can promote vascular smooth muscle cell (VSMC) proliferation, which is pivotal in the pathogenesis and progression of AS. The aim of the present study was to investigate the epigenetic regulatory mechanism of microRNA (miR)‑143‑mediated VSMCs proliferation induced by Hcy. The results of a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphe‑nyltetrazolium bromide assay revealed that VSMC proliferation was increased by 1...
January 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/26562050/reproductive-toxicity-of-low-level-bisphenol-a-exposures-in-a-two-generation-zebrafish-assay-evidence-of-male-specific-effects
#17
Jiangfei Chen, Yanyan Xiao, Zengxin Gai, Rong Li, Zixu Zhu, Chenglian Bai, Robert L Tanguay, Xiaojiang Xu, Changjiang Huang, Qiaoxiang Dong
Bisphenol A (BPA), a high-volume chemical used to make polycarbonate plastic and epoxy resins, is a ubiquitous contaminant in environment and human body. To investigate the reproductive effects of long-term exposure to low concentrations of BPA, a two-generation study was conducted using the aquatic model species of zebrafish. Our findings revealed that exposure to 1nM (0.228μg/L) BPA for continuous two generations resulted in female-biased sex ratio in both F1 and F2 adult population, decreased sperm density, and decreased sperm quality as measured by motility, velocity, ATP content and lipid peroxidation in F1 and F2 males...
December 2015: Aquatic Toxicology
https://www.readbyqxmd.com/read/26547851/presence-of-dna-methyltransferase-activity-and-cpc-methylation-in-drosophila-melanogaster
#18
Chitra S Panikar, Shriram N Rajpathak, Varada Abhyankar, Saniya Deshmukh, Deepti D Deobagkar
Drosophila melanogaster lacks DNMT1/DNMT3 based methylation machinery. Despite recent reports confirming the presence of low DNA methylation in Drosophila; little is known about the methyltransferase. Therefore, in this study, we have aimed to investigate the possible functioning of DNA methyltransferase in Drosophila. The 14 K oligo microarray slide was incubated with native cell extract from adult Drosophila to check the presence of the methyltransferase activity. After incubation under appropriate conditions, the methylated oligo sequences were identified by the binding of anti 5-methylcytosine monoclonal antibody...
December 2015: Molecular Biology Reports
https://www.readbyqxmd.com/read/26531238/dnmts-and-tet-target-memory-associated-genes-after-appetitive-olfactory-training-in-honey-bees
#19
Stephanie D Biergans, C Giovanni Galizia, Judith Reinhard, Charles Claudianos
DNA methylation and demethylation are epigenetic mechanisms involved in memory formation. In honey bees DNA methyltransferase (Dnmt) function is necessary for long-term memory to be stimulus specific (i.e. to reduce generalization). So far, however, it remains elusive which genes are targeted and what the time-course of DNA methylation is during memory formation. Here, we analyse how DNA methylation affects memory retention, gene expression, and differential methylation in stimulus-specific olfactory long-term memory formation...
November 4, 2015: Scientific Reports
https://www.readbyqxmd.com/read/26434589/dnmt3a-mutations-mediate-the-epigenetic-reactivation-of-the-leukemogenic-factor-meis1-in-acute-myeloid-leukemia
#20
H J Ferreira, H Heyn, M Vizoso, C Moutinho, E Vidal, A Gomez, A Martínez-Cardús, L Simó-Riudalbas, S Moran, E Jost, M Esteller
Close to half of de novo acute myeloid leukemia (AML) cases do not exhibit any cytogenetic aberrations. In this regard, distortion of the DNA methylation setting and the presence of mutations in epigenetic modifier genes can also be molecular drivers of the disease. In recent years, somatic missense mutations of the DNA methyltransferase 3A (DNMT3A) have been reported in ~20% of AML patients; however, no obvious critical downstream gene has been identified that could explain the role of DNMT3A in the natural history of AML...
June 9, 2016: Oncogene
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