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active DNA demethylation

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https://www.readbyqxmd.com/read/28811542/identification-replication-and-characterization-of-epigenetic-remodelling-in-the-aging-genome-a-cross-population-analysis
#1
Shuxia Li, Lene Christiansen, Kaare Christensen, Torben A Kruse, Paul Redmond, Riccardo E Marioni, Ian J Deary, Qihua Tan
Aging is a complex biological process regulated by multiple cellular pathways and molecular mechanisms including epigenetics. Using genome-wide DNA methylation data measured in a large collection of Scottish old individuals, we performed discovery association analysis to identify age-methylated CpGs and replicated them in two independent Danish cohorts. The double-replicated CpGs were characterized by distribution over gene regions and location in relation to CpG islands. The replicated CpGs were further characterized by involvement in biological pathways to study their functional implications in aging...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807729/cpg-demethylation-in-the-neurotoxicity-of-1-methyl-4-phenylpyridinium-might-mediate-transcriptional-up-regulation-of-%C3%AE-synuclein-in-sh-sy5y-cells
#2
Jian Yang, Zhaofei Yang, Xuan Wang, Min Sun, Yong Wang, Xiaomin Wang
The accumulation of α-synuclein is the primary pathological hallmark of Parkinson's disease (PD). In PD patients, CpG demethylation of intron-1 has been reported to be associated with α-synuclein up-regulation. Environmental factor, for example neurotoxin, is a major etiological risk factor in PD pathogenesis. However, the role of CpG methylation in neurotoxin-induced PD has not been addressed completely yet. To explore CpG methylation associating with α-synuclein transcription and its underlying mechanisms in the neurotoxin-induced PD pathology, human neuroblastoma SH-SY5Y cells were treated with neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP(+))...
August 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28807014/epigenetic-reprogramming-converts-human-wharton-s-jelly-mesenchymal-stem-cells-into-functional-cardiomyocytes-by-differential-regulation-of-wnt-mediators
#3
G Bhuvanalakshmi, Frank Arfuso, Alan Prem Kumar, Arun Dharmarajan, Sudha Warrier
BACKGROUND: Lineage commitment of mesenchymal stem cells (MSCs) to cardiac differentiation is controlled by transcription factors that are regulated by epigenetic events, mainly histone deacetylation and promoter DNA methylation. Here, we studied the differentiation of human Wharton's jelly MSCs (WJMSCs) into the cardiomyocyte lineage via epigenetic manipulations. METHODS: We introduced these changes using inhibitors of DNA methyl transferase and histone deacetylase, DC301, DC302, and DC303, in various combinations...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28805483/tet1-mediated-dna-demethylation-involves-in-neuron-damage-induced-by-bilirubin-in-vitro
#4
Panhong Gou, Xiaoling Qi, Rui Yuan, Haojie Li, Xiaoling Gao, Junling Wang, Benzhong Zhang
The aim of this study is to identify the role of Tet1-mediated DNA demethylation in the neurotoxicity caused by unconjugated bilirubin (UCB) in vitro. Primary neuronal cells after cultured for 72 h were exposed to UCB (0-100 μmol/L) for 24 h. Following exposure to UCB cytotoxicity was determined with the methyl tetrazolium (MTT) assay, reactive oxygen species (ROS) and caspase-3 activity in neuron cells were measured with the corresponding assay kits. The expression of Tet1 and Klotho was determined with RT-PCR at mRNA level and western blot at protein level...
August 14, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28802167/induction-of-senescence-in-cancer-cells-by-5-aza-2-deoxycytidine-bioinformatics-and-experimental-insights-to-its-targets
#5
Jayarani F Putri, Nashi Widodo, Kazuichi Sakamoto, Sunil C Kaul, Renu Wadhwa
5'-Aza-2'-deoxycytidine (5-Aza-dC) is a demethylating drug that causes genome-wide hypomethylation resulting in the expression of several tumor suppressor genes causing growth arrest of cancer cells. Cancer is well established as a multifactorial disease and requires multi-module therapeutics. Search for new drugs and their approval by FDA takes a long time. Keeping this in view, research on new functions of FDA-approved anticancer drugs is desired to expand the list of multi-module functioning drugs for cancer therapy...
August 2, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28798687/tet2-protects-against-oxldl-induced-huvec-dysfunction-by-upregulating-the-cse-h2s-system
#6
Juan Peng, Zhi-Han Tang, Zhong Ren, Bei He, Yun Zeng, Lu-Shan Liu, Zuo Wang, Dang-Heng Wei, Xi-Long Zheng, Zhi-Sheng Jiang
Ten-eleven translocation-2 (TET2) protein is a DNA demethylase that regulates gene expression through DNA demethylation and also plays important roles in various diseases including atherosclerosis. Endothelial dysfunction represents an early key event in atherosclerotic disease. The cystathionine-γ-lyase (CSE)/hydrogen sulfide (H2S) is a key endogenous system with protective effects on endothelial functions. In this study, we examined how TET2 regulates oxidized low-density lipoprotein (oxLDL)-induced dysfunction of human umbilical vein endothelial cells (HUVECs) and determined the role of the CSE/H2S system...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28794029/coordinate-regulation-of-tet2-and-ebna2-control-dna-methylation-state-of-latent-epstein-barr-virus
#7
Fang Lu, Andreas Wiedmer, Kayla A Martin, Priyankara J M S Wickramasinghe, Andrew V Kossenkov, Paul M Lieberman
Epstein-Barr Virus (EBV) latency and its associated carcinogenesis are regulated by dynamic changes in DNA methylation of both virus and host genomes. We show here that the Ten-Eleven Translocation 2 (TET2) gene, implicated in hydroxymethylation and active DNA demethylation, is a key regulator of EBV latency type DNA methylation patterning. EBV latency types are defined by DNA methylation patterns that restrict expression of viral latency genes. We show that TET2 mRNA and protein expression correlate with the highly demethylated EBV type III latency program permissive for expression of EBNA2, EBNA3s, and LMP transcripts...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28764788/regulation-of-human-glioma-cell-apoptosis-and-invasion-by-mir-152-3p-through-targeting-dnmt1-and-regulating-nf2-mir-152-3p-regulate-glioma-cell-apoptosis-and-invasion
#8
Jin Sun, Xinhua Tian, Junqing Zhang, Yanlin Huang, Xiaoning Lin, Luyue Chen, Shizhong Zhang
BACKGROUND: MiRNAs are involved in aberrant DNA methylation through regulation of DNA methyltransferases (DNMTs) in the pathogenesis and progression of glioblastomas (GBM). MiR-152-3p was down-expressed in human malignancies, and served as a tumor suppressor. Neurofibromatosis type 2 (NF2) was significantly decreased in GBM tissues with a high level of methylation. However, the link between miR-152-3p, DNMT1 and methylation of NF2 in GBM is not clearly established. This study was conducted to detect the mechanism between miR-152-3p, DNMT1 and NF2 in GBM...
August 1, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28760688/the-oligodendrocyte-lineage-transcription-factor-2-olig2-is-epigenetically-regulated-in-acute-myeloid-leukemia
#9
Arzu Yalcin, Marlon Kovarbasic, Julius Wehrle, Rainer Claus, Heiko Becker, Mahmoud Abdelkarim, Verena I Gaidzik, Andrea Schmidts, Ralph Wäsch, Heike L Pahl, Konstanze Döhner, Lars Bullinger, Justus Duyster, Michael Lübbert, Björn Hackanson
DNA methylation differences between normal and cancer tissue resulting in differential expression of genes are a hallmark of acute myeloid leukemia (AML) and can provide growth advantage for malignant cells via silencing of specific genes, e.g. transcription factors. The oligodendrocyte lineage transcription factor 2 (OLIG2) was reported to be differentially methylated and associated with prognosis in AML and - as demonstrated for acute lymphoblastic leukemia and malignant glioma - may play a role in malignant transformation...
July 28, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28760656/norcantharidin-induces-mitochondrial-dependent-apoptosis-through-mcl-1-inhibition-in-human-prostate-cancer-cells
#10
Chu-Liang Lin, Chien-Min Chen, Chia-Liang Lin, Chun-Wen Cheng, Chien-Hsing Lee, Yi-Hsien Hsieh
Norcantharidin (NCTD) is the demethylated form of cantharidin that exhibits anticancer potential in many cancer cell types. Recent reports suggest that NCTD targeting ROS/AMPK and DNA replication signaling pathway could be an effective strategy for the treatment of PCa cells. However, supportive evidence is limited to the effect of NCTD that induction of apoptosis through suppression of the Mcl-1. Here, we show that NCTD induced PCa cell apoptosis and triggered caspase activation, which was associated with mitochondria dysfunction...
July 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28758879/genome-wide-analysis-of-cytosine-dna-methylation-revealed-salicylic-acid-promotes-defense-pathways-over-seedling-development-in-pearl-millet
#11
Baba Ngom, Ibrahima Sarr, Josphert Kimatu, Edward Mamati, Ndjido Ardo Kane
Cytosine DNA methylation is an epigenetic regulatory system used by plants to control gene expression. Methylation pattern always changes after abiotic stresses, pathogens and pest infections or after a treatment with salicylic acid (SA). The latter is a key player in plant development and defense against insect herbivores, pathogens, and abiotic stresses. The roles of SA on the methylation patterns and the plant development were carried out in four pearl millet (Pennisetum glaucum) varieties. Seedlings of four early-flowering photosensitive genotypes (PMS3, PMI8, PMG, and PMT2) were grown on MS medium supplemented with null or different doses of SA...
July 31, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28758855/targeting-dna-hypermethylation-computational-modeling-of-dna-demethylation-treatment-of-acute-myeloid-leukemia
#12
Jens Przybilla, Lydia Hopp, Michael Lübbert, Markus Loeffler, Joerg Galle
In acute myeloid leukemia (AML) DNA hypermethylation of gene promoters is frequently observed and often correlates with a block of differentiation. Treatment of AML patients with DNA methyltransferase inhibitors results in global hypomethylation of genes and, thereby, can lead to a reactivation of the differentiation capability. Unfortunately, after termination of treatment both hypermethylation and differentiation block return in most cases. Here, we apply, for the first time, a computational model of epigenetic regulation of transcription in order to: i) provide a mechanistic understanding of the DNA (de-) methylation process in AML and; ii) improve DNA demethylation treatment strategies...
July 31, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28757075/dna-demethylation-pattern-of-in-vitro-fertilized-and-cloned-porcine-pronuclear-stage-embryos
#13
Xiaowei Nie, Qiang Liu, Ronggen Wang, Wenjie Sheng, Xiaokang Li, Manling Zhang, Yong Jin, Lihua Zhao, Daorong Hou, Ning Yang, Zhaoqiang Wu, Yifan Dai, Rongfeng Li
Recent studies in mice showed that the Ten-eleven translocation Enzymes (TET) family is involved in the active DNA demethylation. The isotype TET-3 is responsible for the conversion of 5mc (5-methylcytosine) to 5hmc (5-hydroxymethylcytosine) at the pronuclear stages of mouse embryo. This study was performed to investigate the pattern of methylation change and the role of TET family in the demethylation process of porcine in-vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT) derived embryo. Bisulfite-sequencing PCR (BSP) and DNA glucosylation and digestion before quantitative PCR (qGluMS-PCR) were done to evaluate the exact change of methylation during porcine pronuclear stages...
July 27, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28750405/untargeted-dna-demethylation-therapy-neither-prevents-nor-attenuates-ischemia-reperfusion-induced-renal-fibrosis
#14
Benjamin A Vervaet, Lies Moonen, Lode Godderis, Katrien Poels, Patrick C D'Haese
BACKGROUND: Current treatment options for chronic kidney disease (CKD) are limited and their focus is on slowing its progression by addressing comorbidities. Fibrosis, the common histopathological process in CKD, is a major therapeutic research target. In CKD, fibroblasts are terminally activated due to alterations in their DNA-methylation pattern, particularly hypermethylation. Preventing the copying of pathological DNA-methylation patterns in proliferating fibroblasts could be a new effective therapeutic strategy for treating CKD...
July 28, 2017: Nephron
https://www.readbyqxmd.com/read/28745936/5-hydroxymethylcytosine-in-dna-repair-a-new-player-or-a-red-herring
#15
Omar L Kantidze, Sergey V Razin
Active DNA demethylation performed by ten-eleven translocation (TET) enzymes produces 5-hydroxymethylcytosines, 5-formylcytosines, and 5-carboxylcytosines. Recent observations suggest that 5-hydroxymethylcytosine is a stable epigenetic mark rather than merely an intermediate of DNA demethylation. However, the clear functional role of this new epigenetic player is elusive. The contribution of 5-hydroxymethylation to DNA repair is being discussed currently. Recently Jiang and colleagues have demonstrated that DNA damage response-activated ATR kinase phosphorylates TET3 in mammalian cells and promotes DNA demethylation and 5-hydroxymethylcytosine accumulation...
July 26, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28744818/epigenetic-modification-of-tle1-induce-abnormal-differentiation-in-diabetic-mice-intestinal-epithelium
#16
Ji-Hao Xu, Guang-Cheng Chen, Can-Ze Huang, Di Cheng, Ting-Feng Wu, Si-Yi Wang, Jie-Yao Li, Tao Yu, Qi-Kui Chen
The intestinal epithelium cells (IECs) in diabetes mellitus (DM) patients have been proven to be abnormally differentiated. During the differentiation of IECs, epigenetic modification acts as an important regulator. In this study, we aimed to examine the epigenetic alteration of Transducin-like Enhancer of Split 1 (TLE1), a multitask transcriptional co-repressor, contributing to the differentiation homeostasis in IECs of DM mice. The IECs of type 2 diabetic mice model were isolated and collected. Methylation states of whole genomic DNA promoter regions were investigated by microarray...
July 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28743002/drosophila-histone-demethylase-kdm4a-has-enzymatic-and-non-enzymatic-roles-in-controlling-heterochromatin-integrity
#17
Serafin U Colmenares, Joel M Swenson, Sasha A Langley, Cameron Kennedy, Sylvain V Costes, Gary H Karpen
Eukaryotic genomes are broadly divided between gene-rich euchromatin and the highly repetitive heterochromatin domain, which is enriched for proteins critical for genome stability and transcriptional silencing. This study shows that Drosophila KDM4A (dKDM4A), previously characterized as a euchromatic histone H3 K36 demethylase and transcriptional regulator, predominantly localizes to heterochromatin and regulates heterochromatin position-effect variegation (PEV), organization of repetitive DNAs, and DNA repair...
July 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28731456/upregulation-of-tet-activity-with-ascorbic-acid-induces-epigenetic-modulation-of-lymphoma-cells
#18
N Shenoy, T Bhagat, E Nieves, M Stenson, J Lawson, G S Choudhary, T Habermann, G Nowakowski, R Singh, X Wu, A Verma, T E Witzig
The Ten Eleven Translocation (TET) enzymes have been found to be mutated in both diffuse large B-cell (DLBCL) and peripheral T-cell (PTCL) lymphomas resulting in DNA hypermethylation. Recent studies in embryonal stem cells showed that ascorbic acid (AA) is a cofactor for TET with a binding site at the catalytic domain, and enhances TET activity. We hypothesized that AA could potentially enhance TET activity in lymphoma cells to cause DNA demethylation, reactivate expression of tumor suppressor genes and enhance chemosensitivity...
July 21, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28715893/5-formyl-and-5-carboxydeoxycytidines-do-not-cause-accumulation-of-harmful-repair-intermediates-in-stem-cells
#19
René Rahimoff, Olesea Kosmatchev, Angie Kirchner, Toni Pfaffeneder, Fabio Spada, Victor Brantl, Markus Müller, Thomas Carell
5-Formyl-dC (fdC) and 5-carboxy-dC (cadC) are newly discovered bases in the mammalian genome that are supposed to be substrates for base excision repair (BER) in the framework of active demethylation. The bases are recognized by the monofunctional thymine DNA glycosylase (Tdg), which cleaves the glycosidic bond of the bases to give potentially harmful abasic sites (AP-sites). Because of the turnover of fdC and cadC during cell state transitions, it is an open question to what extent such harmful AP-sites may accumulate during these processes...
July 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28714938/taxifolin-activates-the-nrf2-anti-oxidative-stress-pathway-in-mouse-skin-epidermal-jb6-p-cells-through-epigenetic-modifications
#20
Haixue Kuang, Zhenqiu Tang, Chengyue Zhang, Zhibin Wang, Wenji Li, Chunjuan Yang, Qiuhong Wang, Bingyou Yang, Ah-Ng Kong
Nuclear factor erythroid-2 related factor 2 (Nrf2) is a vital transcription factor that regulates the anti-oxidative defense system. Previous reports suggested that the expression of the Nrf2 gene can be regulated by epigenetic modifications. The potential epigenetic effect of taxifolin (TAX), a potent cancer chemopreventive agent, in skin cancer chemoprotection is unknown. In this study, we investigated how Nrf2 is epigenetically regulated by TAX in JB6 P+ cells. TAX was found to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced colony formation of JB6 P+ cells...
July 17, 2017: International Journal of Molecular Sciences
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