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Dna hydroxymethylation

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https://www.readbyqxmd.com/read/28230192/an-endoparasitoid-wasp-influences-host-dna-methylation
#1
Sunil Kumar, Yonggyun Kim
Parasitism by endoparasitoid wasps changes the expression of various host genes, and alters host immune and developmental processes. However, it is not clearly understood how parasitism changes host gene expression in a whole genome scale. This study focused on an epigenetic control of Cotesia plutellae, an endoparasitoid wasp, against its host, Plutella xylostella. Two DNA methyltransferases (DNMT-1 and DNMT-2) are encoded in the genome of P. xylostella. In addition, methyl-binding domain proteins (MBDs) and DNA demethylation factor, ten-eleven translation protein (TET) are encoded...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229992/increased-5-hydroxymethylcytosine-and-ten-eleven-translocation-protein-expression-in-ultraviolet-b-irradiated-hacat-cells
#2
Dan Wang, Jin-Hua Huang, Qing-Hai Zeng, Can Gu, Shu Ding, Jian-Yun Lu, Jing Chen, Sheng-Bo Yang
BACKGROUND: DNA hydroxymethylation refers to a chemical modification process in which 5-methylcytosine (5mC) is catalyzed to 5- hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins. Recent studies have revealed that aberrant TETs expression or 5hmC level may play important roles in the occurrence and development of various pathological and physiological processes including cancer and aging. This study aimed to explore the relation between aberrant DNA hydroxymethylation with skin photoaging and to investigate the levels of TETs, 5mC, and 5hmC expression 24 h after 40 mJ/cm2 and 80 mJ/cm2 doses of ultraviolet B (UVB) irradiation to HaCaT cells...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28225433/the-role-of-5-hydroxymethylcytosine-in-melanoma
#3
Feng-Juan Li, Li-Ming Li, Rui-Hua Zhang, Cui Xu, Pan Zhou, Jia Long, Gang Hu, Ming-Jun Jiang
Malignant melanoma is a highly aggressive neoplasia of melanocytic origin. In part because of the lack of effective treatment methods, the incidence and mortality rates of this disease continue to increase. Rapidly accumulating evidence suggests that dysregulation of epigenetic mechanisms, including DNA methylation/demethylation, chromatin modification, and remodeling, and diverse activities of noncoding RNAs, play a central role in the pathogenesis of melanoma. The epigenetic mark 5-hydroxymethylcytosine (5-hmC) has attracted interest since 2009, when it was shown that ten-eleven translocation proteins can enzymatically convert 5-methylcytosine into 5-hmC, a key intermediate of DNA demethylation...
February 20, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28220902/twist1-induces-mmp3-expression-through-up-regulating-dna-hydroxymethylation-and-promotes-catabolic-responses-in-human-chondrocytes
#4
Joe Hasei, Takeshi Teramura, Toshiyuki Takehara, Yuta Onodera, Takuro Horii, Merissa Olmer, Izuho Hatada, Kanji Fukuda, Toshifumi Ozaki, Martin K Lotz, Hiroshi Asahara
The objective was to investigate the levels of TWIST1 in normal and OA cartilage and examine its role in regulating gene expression in chondrocytes. Human cartilage tissues and chondrocytes were obtained at autopsy from normal knee joints and from OA-affected joints at the time of total knee arthroplasty. TWIST1 expression was increased in human OA knee cartilage compared to normal knee cartilage. TWIST1 induced matrix metalloproteinase 3 (MMP3) expression without direct binding to MMP3 promoter and increased the 5-hydroxymethylcytosine (5hmC) level at the MMP3 promoter...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28218476/overexpression-of-tet-dioxygenases-in-seminomas-associates-with-low-levels-of-dna-methylation-and-hydroxymethylation
#5
Martina Benešová, Kateřina Trejbalová, Dana Kučerová, Zdenka Vernerová, Tomáš Hron, Arpád Szabó, Rachel Amouroux, Petr Klézl, Petra Hajkova, Jiří Hejnar
Germ cell tumors and particularly seminomas reflect the epigenomic features of their parental primordial germ cells, including genomic DNA hypomethylation and expression of pluripotent cell markers. Because the DNA hypomethylation might be a result of TET dioxygenase activity, we examined expression of TET1-3 enzymes and the level of their product, 5-hydroxymethylcytosine, in a panel of histologically characterized seminomas and non-seminomatous germ cell tumors. Expression of TET dioxygenase mRNAs was quantified by real-time PCR...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28212500/cyto-genotoxic-and-dna-methylation-changes-induced-by-different-crystal-phases-of-tio2-np-in-bronchial-epithelial-16-hbe-cells
#6
Manosij Ghosh, Deniz Öner, Radu-Corneliu Duca, Stevan M Cokic, Sven Seys, Stef Kerkhofs, Kirsten Van Landuyt, Peter Hoet, Lode Godderis
With the increase in use of TiO2-np, a better understanding of their safety is important. In the present study the effect of different crystal phases of TiO2-np (anatase, rutile and anatase: rutile mixture; 20-26nm) were studied for cyto-genotoxicity and global DNA methylation and hydroxymethylation. Cytotoxic response was observed at a concentration of 25μg/ml for the particles tested. Results of comet and micronucleus (with and without CytB) assays revealed significant genotoxic effect of these particles...
February 10, 2017: Mutation Research
https://www.readbyqxmd.com/read/28193047/accurate-direct-and-high-throughput-analyses-of-a-broad-spectrum-of-endogenously-generated-dna-base-modifications-with-isotope-dilution-two-dimensional-ultraperformance-liquid-chromatography-with-tandem-mass-spectrometry-possible-clinical-implication
#7
Daniel Gackowski, Marta Starczak, Ewelina Zarakowska, Martyna Modrzejewska, Anna Szpila, Zbigniew Banaszkiewicz, Ryszard Olinski
Our hereby presented methodology is suitable for reliable assessment of the most common unavoidable DNA modifications which arise as a product of fundamental metabolic processes. 8-Oxoguanine, one of the oxidatively modified DNA bases, is a typical biomarker of oxidative stress. A noncanonical base, uracil, may be also present in small quantities in DNA. A set of ten-eleven translocation (TET) proteins are involved in oxidation of 5-methylcytosine to 5-hydroxymethylcytosine which can be further oxidized to 5-formylcytosine and 5-carboxycytosine...
December 20, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/28192139/vitamin-c-down-regulate-apo-a-expression-via-tet2-dependent-dna-demethylation-in-hepg2-cells
#8
Kai Qu, Xiao-Feng Ma, Guo-Hua Li, Hai Zhang, Ya-Mi Liu, Kai Zhang, Jun-Fa Zeng, Jian-Jun Lei, Dang-Heng Wei, Zuo Wang
Lipoprotein(a)[Lp(a)] is a risk factor for coronary heart diseases. However, the metabolism of this protein remains poorly understood. Efficient and specific drugs that can decrease high plasma levels of Lp(a) have not been developed yet. Vitamin C is responsible for maintaining the catalytic activity of a group of iron and 2-oxoglutarate (2OG)-dependent dioxygenases and induces the generation of 5-hydroxymethylcytosine (5hmC) via Ten-eleven translocation (Tet) dioxygenases. In addition, It has been reported vitamin C deficiency induces atherosclerosis and increases Lp(a) and apo(a) plasma levels in Lp(a)+ mice...
February 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28192098/anti-leukemic-effects-of-hdaci-belinostat-and-hmti-3-deazaneplanocin-a-on-human-acute-promyelocytic-leukemia-cells
#9
Giedrė Valiulienė, Ieva Stirblytė, Monika Jasnauskaitė, Veronika Borutinskaitė, Rūta Navakauskienė
Development of acute myeloid leukemia is usually sustained by deregulated epigenome. Alterations in DNA methylation and histone modifications are common manifestations of the disease. Acute promyelocytic leukemia (APL) is not an exception. Therefore, drugs that target epigenetic processes suggest an appealing strategy for APL treatment. In this study we tested the anti-leukemic activity of histone deacetylase inhibitor (HDACi) Belinostat (PXD101, (2E)-N-Hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide), and histone methyltransferase inhibitor (HMTi) 3-Deazaneplanocin A (DZNep, 5R-(4-amino-1H-imidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)-3-cyclopentene-1S,2R-diol) combined with retinoic acid (RA) in APL cells NB4 and HL-60...
February 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28178884/improved-post-thaw-function-and-epigenetic-changes-in-mesenchymal-stromal-cells-cryopreserved-using-multicomponent-osmolyte-solutions
#10
Kathryn Pollock, Rebekah Samsonraj, Amel Dudakovic, Roman Thaler, Aron Stumbras, David McKenna, Peter Dosa, Andre van Wijnen, Allison Hubel
Current methods for freezing mesenchymal stromal cells (MSCs) result in poor post-thaw function, which limits the clinical utility of these cells. This investigation develops a novel approach to preserve MSCs using combinations of sugars, sugar alcohols and small molecule additives. MSCs frozen using these solutions exhibit improved post-thaw attachment and a more normal alignment of the actin cytoskeleton compared to cells exposed to dimethylsulfoxide (DMSO). Osteogenic and chondrogenic differentiation assays show that cells retain their mesenchymal lineage properties...
February 8, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28176928/n-3-hydroxymethyl-%C3%AE-carboline-1-yl-ethyl-2-yl-l-phe-development-toward-a-nanoscaled-antitumor-drug-capable-of-treating-complicated-thrombosis-and-inflammation
#11
Jianhui Wu, Ming Zhao, Yuji Wang, Yaonan Wang, Haimei Zhu, Shurui Zhao, Lin Gui, Xiaoyi Zhang, Shiqi Peng
It is well documented that the surfaces of cancer cells, activated platelets and inflammatory cells are rich in P-selectin. N-(3-hydroxymethyl-β-carboline-1-yl-ethyl-2-yl)-l-Phe (HMCEF) is a P-selectin inhibitor capable of simultaneously inhibiting thrombosis and inflammation. Based on the knowledge that P-selectin is a common target for antithrombotic, anti-inflammatory and antitumor drugs, the aim of this study article was to estimate the possibility of HMCEF as a nanoscaled antitumor drug. Images of transmission electron micro scopy, scanning electron microscopy and atomic force microscopy proved that HMCEF forms nanoparticles with a diameter of <120 nm that promote delivery in blood circulation...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28153600/role-of-oxidative-stress-and-dna-hydroxymethylation-in-the-neurotoxicity-of-fine-particulate-matter
#12
Hongying Wei, Yan Feng, Fan Liang, Wei Cheng, Xiaomeng Wu, Ren Zhou, Yan Wang
Epidemiological studies have implicated fine particulate matter (PM2.5) as a risk factor for neurodegenerative diseases and neurodevelopmental disorders. However, the underlying molecular mechanisms and the influences of different components remain largely elusive. Here, we extended our previous work to investigate the role of oxidative stress and DNA hydroxymethylation in neuronal pathology of PM2.5. We found PM2.5 and its extracts (water-soluble extracts, organic extracts and carbon core component) differentially caused cell cycle arrest, cell apoptosis and the cell proliferation inhibition in neuronal cells...
January 30, 2017: Toxicology
https://www.readbyqxmd.com/read/28125883/detection-of-pyrrolizidine-alkaloid-dna-adducts-in-livers-of-cattle-poisoned-with-heliotropium-europaeum
#13
Peter P Fu, Qingsu Xia, Xiaobo He, Shimon Barel, Nir Edery, Frederick A Beland, Jakob A Shimshoni
Pyrrolizidine alkaloids are among the most common poisonous plants affecting livestock, wildlife, and humans. Exposure of humans and livestock to toxic pyrrolizidine alkaloids through the intake of contaminated food and feed may result in poisoning, leading to devastating epidemics. During February 2014, 73 mixed breed female beef cows from the Galilee region of Israel were accidently fed pyrrolizidine alkaloid contaminated hay for 42 days, resulting in the sudden death of 24 cows over a period of 63 days. The remaining cows were slaughtered 2...
February 10, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28125225/dynamics-of-a-dna-mismatch-site-held-in-confinement-discriminate-epigenetic-modifications-of-cytosine
#14
Robert P Johnson, Aaron M Fleming, Rukshan T Perera, Cynthia J Burrows, Henry S White
The identification and discrimination of four epigenetic modifications to cytosine in the proposed active demethylation cycle is demonstrated at the single-molecule level, without the need for chemical pre-treatment or labeling. The wild-type protein nanopore alpha-hemolysin is used to capture individual DNA duplexes containing a single cytosine-cytosine mismatch. The mismatch is held at the latch constriction of alpha-hemolysin, which is used to monitor the kinetics of base flipping at the mismatch site. Base flipping and the subsequent interactions between the DNA and the protein are dramatically altered when one of the cytosine bases is replaced with methyl-, hydroxymethyl-, formyl-, or carboxylcytosine...
January 26, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28115522/the-5-hydroxymethylcytosine-5hmc-reader-uhrf2-is-required-for-normal-levels-of-5hmc-in-mouse-adult-brain-and-spatial-learning-and-memory
#15
Ruoyu Chen, Qiao Zhang, Xiaoya Duan, Philippe York, Guo-Dong Chen, Pengcheng Yin, Haijun Zhu, Meichen Xu, Peilin Chen, Qihan Wu, Dali Li, Jacques Samarut, Guoliang Xu, Pumin Zhang, Xiaohua Cao, Jiwen Li, Jiemin Wong
UHRF2 has been implicated as a novel regulator for both DNA methylation (5mC) and hydroxymethylation (5hmC), but its physiological function and role in DNA methylation/hydroxymethylation are unknown. Here we show that in mice Uhrf2 is more abundantly expressed in the brain and a few other tissues. Uhrf2 knockout mice are viable, fertile and exhibit no gross defect. Although there is no significant change of DNA methylation, the Uhrf2 null mice exhibit a reduction of 5hmC in the brain including cortex and hippocampus...
January 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100169/medium-throughput-bisulfite-sequencing-for-accurate-detection-of-5-methylcytosine-and-5-hydroxymethylcytosine
#16
Gary G Chen, Jeffrey A Gross, Pierre-Eric Lutz, Kathryn Vaillancourt, Gilles Maussion, Alexandre Bramoulle, Jean-François Théroux, Elena S Gardini, Ulrike Ehlert, Geneviève Bourret, Aurélie Masurel, Pierre Lepage, Naguib Mechawar, Gustavo Turecki, Carl Ernst
BACKGROUND: Epigenetic modifications of DNA, such as 5-methylcytosine and 5-hydroxymethycytosine, play important roles in development and disease. Here, we present a cost-effective and versatile methodology for the analysis of DNA methylation in targeted genomic regions, which comprises multiplexed, PCR-based preparation of bisulfite DNA libraries followed by customized MiSeq sequencing. RESULTS: Using bisulfite and oxidative bisulfite conversion of DNA, we have performed multiplexed targeted sequencing to analyse several kilobases of genomic DNA in up to 478 samples, and achieved high coverage data of 5-methylcytosine and 5-hydroxymethycytosine at single-base resolution...
January 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28089213/a-genome-wide-profiling-of-brain-dna-hydroxymethylation-in-alzheimer-s-disease
#17
Jinying Zhao, Yun Zhu, Jingyun Yang, Lin Li, Hao Wu, Philip L De Jager, Peng Jin, David A Bennett
INTRODUCTION: DNA methylation is a key epigenetic mechanism in brain aging and Alzheimer's disease (AD). The newly discovered 5-hydroxymethylcytosine mediates DNA demethylation, is highly abundant in the brain, and is dynamically regulated by life experiences. However, little is known about its genome-wide patterns and potential role in AD. METHODS: Using a genome-wide capture followed by high-throughput sequencing, we studied the genome-wide distribution of 5-hydroxymethylcytosine at specific genomic loci in human AD brain and identified differentially hydroxymethylated regions (DhMRs) associated with AD pathology...
January 6, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28079150/sustained-kidney-biochemical-derangement-in-treated-experimental-diabetes-a-clue-to-metabolic-memory
#18
Antonio Anax F de Oliveira, Tiago F de Oliveira, Larissa L Bobadilla, Camila C M Garcia, Carolina Maria Berra, Nadja C de Souza-Pinto, Marisa H G Medeiros, Paolo Di Mascio, Roberto Zatz, Ana Paula de M Loureiro
The occurrence of biochemical alterations that last for a long period of time in diabetic individuals even after adequate handling of glycemia is an intriguing phenomenon named metabolic memory. In this study, we show that a kidney pathway is gradually altered during the course of diabetes and remains persistently changed after late glycemic control in streptozotocin-induced diabetic rats. This pathway comprises an early decline of uric acid clearance and pAMPK expression followed by fumarate accumulation, increased TGF-β expression, reduced PGC-1α expression, and downregulation of methylation and hydroxymethylation of mitochondrial DNA...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28074830/tet1-in-nucleus-accumbens-opposes-depression-and-anxiety-like-behaviors
#19
Jian Feng, Catherine J Pena, Immanuel Purushothaman, Olivia Engmann, Deena Walker, Amber N Brown, Orna Issler, Marie Doyle, Eileen Harrigan, Ezekiell Mouzon, Vincent Vialou, Li Shen, Meelad M Dawlaty, Rudolf Jaenisch, Eric J Nestler
Depression is a leading cause of disease burden, yet current therapies fully treat <50% of affected individuals. Increasing evidence implicates epigenetic mechanisms in depression and antidepressant action. Here we examined a possible role for the DNA dioxygenase, ten-eleven translocation protein 1 (TET1), in depression-related behavioral abnormalities. We applied chronic social defeat stress, an ethologically validated mouse model of depression-like behaviors, and examined Tet1 expression changes in nucleus accumbens (NAc), a key brain reward region...
January 25, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28064078/novel-indolizino-8-7-b-indole-hybrids-as-anti-small-cell-lung-cancer-agents-regioselective-modulation-of-topoisomerase-ii-inhibitory-and-dna-crosslinking-activities
#20
Sue-Ming Chang, Wilson Christian, Ming-Hsi Wu, Tai-Lin Chen, Yi-Wen Lin, Ching-Shu Suen, Hima Bindu Pidugu, Dilip Detroja, Anamik Shah, Ming-Jing Hwang, Tsann-Long Su, Te-Chang Lee
A novel series of bis(hydroxymethyl)indolizino[8,7-b]indole hybrids composed of β-carboline (topoisomerase I/II inhibition) and bis(hydroxymethyl)pyrrole (DNA cross-linking) are synthesized for antitumor evaluation. Of tumor cell lines tested, small cell lung cancer (SCLC) cell lines are the most sensitive to the newly synthesized compounds. These hybrids induce cell cycle arrest at the G2/M phase, trigger tumor cell apoptotic death, and display diverse mechanisms of action involving topoisomerase II (Topo II) inhibition and induction of DNA cross-linking...
February 15, 2017: European Journal of Medicinal Chemistry
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