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https://www.readbyqxmd.com/read/28441774/brain-derived-neurotrophic-factor-mediated-perfluorooctane-sulfonate-induced-neurotoxicity-via-epigenetics-regulation-in-sk-n-sh-cells
#1
Xin-Xin Guo, Qing-Zhi He, Wu Li, Ding-Xin Long, Xiao-Yuan Pan, Cong Chen, Huai-Cai Zeng
Perfluorooctane sulfonate (PFOS), a new kind of persistent organic pollutant, is widely distributed in the environment and exists in various organisms, where it is also a neurotoxic compound. However, the potential mechanism of its neurotoxicity is still unclear. To examine the role of epigenetics in the neurotoxicity induced by PFOS, SK-N-SH cells were treated with different concentrations of PFOS or control medium (0.1% DMSO) for 48 h. The mRNA levels of DNA methyltransferases (DNMTs) and Brain-derived neurotrophic factor (BDNF), microRNA-16, microRNA-22, and microRNA-30a-5p were detected by Quantitative PCR (QPCR)...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28419930/design-synthesis-and-anticancer-potential-of-nsc-319745-hydroxamic-acid-derivatives-as-dnmt-and-hdac-inhibitors
#2
Zigao Yuan, Qinsheng Sun, Dan Li, Shuangshuang Miao, Shaopeng Chen, Lu Song, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) are important epigenetic targets during anticancer drug development. Recent study indicates that DNMT inhibitors and HDAC inhibitors display synergistic effects in certain cancers, therefore, development of molecules targeting both DNMT and HDAC is of therapeutic advantage against these cancers. Based on the structure of DNMT inhibitor NSC-319745 and the pharmacophore characteristics of HDAC inhibitors, a series of hydroxamic acid derivatives of NSC-319745 were designed and synthesized as DNMT and HDAC multifunctional inhibitors...
April 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28349196/decreased-mrna-expression-levels-of-dna-methyltransferases-type-1-and-3a-in-systemic-lupus-erythematosus
#3
Mariusz J Nawrocki, Dominik Majewski, Mariusz Puszczewicz, Paweł P Jagodziński
OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease characterized by the presence of autoantibodies directed against nuclear antigens and by chronic inflammation. Although the etiology of SLE remains unclear, the influence of environment factors, which is largely reflected by the epigenetic mechanisms, with DNA methylation changes in particular, is generally considered as main players in the pathogenesis of SLE. We studied DNA methyltransferases' (DNMTs) type 1, 3A and 3B transcript levels in peripheral blood mononuclear cells from patients diagnosed with systemic lupus erythematosus and from the healthy control subjects...
May 2017: Rheumatology International
https://www.readbyqxmd.com/read/28338387/comparison-of-the-effects-of-curcumin-and-rg108-on-ngf-induced-pc-12%C3%A2-adh-cell-differentiation-and-neurite-outgrowth
#4
Miriş Dikmen
DNA methyltransferases (DNMTs) are promising epigenetic targets for the development of novel drugs, especially for neurodegenerative disorders. In recent years, there has been increased interest in small molecules that can cross the blood-brain barrier for the treatment of neurodegenerative diseases. Therefore, comparing the neuronal differentiative effects of a natural compound curcumin and a synthetic small molecule RG108 was the aim of this study. The effects of curcumin and RG108 on neuronal differentiation and neurite outgrowth were investigated in the PC-12 Adh cell line...
April 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28336320/preliminary-research-on-dna-methylation-changes-during-murine-palatogenesis-induced-by-tcdd
#5
Chen Wang, Xin-Gang Yuan, Cui-Ping Liu, Sha-Na Zhai, Ding-Wen Zhang, Yue-Xian Fu
2,3,7,8-Tetrachlrodibenzo-p-dioxin (TCDD) has been shown to induce cleft palate through growth factor and receptor expression changes during palatogenesis. DNA methylation is an important epigenetic modification that can regulate gene expressions and may be involved in TCDD-induced cleft palate. In this study, we investigated the effects of TCDD on the global and CpG DNA methylation status and the expression levels of DNA methyltransferases (Dnmts) in palate tissue of fetal mice. Pregnant C57BL/6J mice were administered with corn oil or TCDD 28 μg/kg at gestation day 10...
February 12, 2017: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/28323001/dna-methyltransferase-1-rs16999593-genetic-polymorphism-decreases-risk-in-patients-with-transposition-of-great-arteries
#6
Liming Lei, Haoming Lin, Shilong Zhong, Zhiwei Zhang, Jimei Chen, Xiyong Yu, Xiaoqing Liu, Cheng Zhang, Zhiqiang Nie, Jian Zhuang
Complete transposition of the great arteries (TGA) is the most frequent cyanotic heart defect diagnosed in neonates. However, the exact etiology of TGA is unknown. The aim of the present study was to assess the association of TGA pathogenesis with single nucleotide polymorphisms (SNPs) in DNA methyltransferases (DNMTs)-1 and 3a- in Chinese children. We genotyped 5 SNPs (rs16999593, rs16999358, and rs2228611 in DNMT1; and rs2276599 and rs2276598 in DNMT3A) in 206 patients with complete TGA and 252 healthy children...
June 5, 2017: Gene
https://www.readbyqxmd.com/read/28321157/hsa-mir-183-is-frequently-methylated-and-related-to-poor-survival-in-human-hepatocellular-carcinoma
#7
Sumadi Lukman Anwar, Till Krech, Britta Hasemeier, Elisa Schipper, Nora Schweitzer, Arndt Vogel, Hans Kreipe, Reena Buurman, Britta Skawran, Ulrich Lehmann
AIM: To screen clinically relevant microRNAs (miRNAs) silenced by DNA methylation in human hepatocellular carcinoma (HCC). METHODS: Knockdown of DNA methyltransferases (DNMTs) using siRNAs and miRNA profiling in HCC cell lines were performed to identify DNA hypermethylation-mediated miRNA downregulation. Confirmation using individual quantitative real-time PCR (qRT-PCR) assays was then performed followed by DNA methylation quantification at the promoter of the miRNA genes...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28300471/decoupling-of-dna-methylation-and-activity-of-intergenic-line-1-promoters-in-colorectal-cancer
#8
Natasha Vafadar-Isfahani, Christina Parr, Lara E McMillan, Juliane Sanner, Zhao Yeo, Stephen Saddington, Oliver Peacock, Hazel A Cruickshanks, Richard R Meehan, Jonathan N Lund, Cristina Tufarelli
Hypomethylation of LINE-1 repeats in cancer has been proposed as the main mechanism behind their activation; this assumption, however, was based on findings from early studies that were biased towards young and transpositionally active elements. Here, we investigate the relationship between methylation of two intergenic, transpositionally inactive LINE-1 elements and expression of the LINE-1 chimeric transcript (LCT) 13 and LCT14 driven by their antisense promoters (L1-ASP). Our data from DNA modification, expression, and 5'RACE analyses suggest that colorectal cancer methylation in the regions analyzed is not always associated with LCT repression...
March 16, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28278502/kaempferol-modulates-dna-methylation-and-downregulates-dnmt3b-in-bladder-cancer
#9
Wei Qiu, Jun Lin, Yichen Zhu, Jian Zhang, Liping Zeng, Ming Su, Ye Tian
BACKGROUND: Genomic DNA methylation plays an important role in both the occurrence and development of bladder cancer. Kaempferol (Kae), a natural flavonoid that is present in many fruits and vegetables, exhibits potent anti-cancer effects in bladder cancer. Similar to other flavonoids, Kae possesses a flavan nucleus in its structure. This structure was reported to inhibit DNA methylation by suppressing DNA methyltransferases (DNMTs). However, whether Kae can inhibit DNA methylation remains unclear...
March 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28266632/specific-cpg-hyper-methylation-leads-to-ankrd26-gene-down-regulation-in-white-adipose-tissue-of-a-mouse-model-of-diet-induced-obesity
#10
Gregory A Raciti, Rosa Spinelli, Antonella Desiderio, Michele Longo, Luca Parrillo, Cecilia Nigro, Vittoria D'Esposito, Paola Mirra, Francesca Fiory, Vincenzo Pilone, Pietro Forestieri, Pietro Formisano, Ira Pastan, Claudia Miele, Francesco Beguinot
Epigenetic modifications alter transcriptional activity and contribute to the effects of environment on the individual risk of obesity and Type 2 Diabetes (T2D). Here, we have estimated the in vivo effect of a fat-enriched diet (HFD) on the expression and the epigenetic regulation of the Ankyrin repeat domain 26 (Ankrd26) gene, which is associated with the onset of these disorders. In visceral adipose tissue (VAT), HFD exposure determined a specific hyper-methylation of Ankrd26 promoter at the -436 and -431 bp CpG sites (CpGs) and impaired its expression...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28250235/methylation-dynamics-during-folliculogenesis-and-early-embryo-development-in-sheep
#11
Laura Masala, Giovanni Pietro Burrai, Emanuela Bellu, Federica Ariu, Luisa Bogliolo, Sergio Ledda, Daniela Bebbere
Genome-wide DNA methylation reprogramming occurs during mammalian gametogenesis and early embryogenesis. Post-fertilization demethylation of paternal and maternal genomes is considered to occur by an active and passive mechanism, respectively, in most mammals but sheep; in this species no loss of methylation was observed in either pronucleus. Post-fertilization reprogramming relies on methylating and de-methylating enzymes and co-factors that are stored during oocyte growth, concurrently with the re-methylation of the oocyte itself...
March 1, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28240742/dna-methylation-mediates-neural-processing-after-odor-learning-in-the-honeybee
#12
Stephanie D Biergans, Charles Claudianos, Judith Reinhard, C Giovanni Galizia
DNA methyltransferases (Dnmts) - epigenetic writers catalyzing the transfer of methyl-groups to cytosine (DNA methylation) - regulate different aspects of memory formation in many animal species. In honeybees, Dnmt activity is required to adjust the specificity of olfactory reward memories and bees' relearning capability. The physiological relevance of Dnmt-mediated DNA methylation in neural networks, however, remains unknown. Here, we investigated how Dnmt activity impacts neuroplasticity in the bees' primary olfactory center, the antennal lobe (AL) an equivalent of the vertebrate olfactory bulb...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28158319/dnmt-1-maintains-hypermethylation-of-cag-promoter-specific-region-and-prevents-expression-of-exogenous-gene-in-fat-1-transgenic-sheep
#13
Chunrong Yang, Xueying Shang, Lei Cheng, Lei Yang, Xuefei Liu, Chunling Bai, Zhuying Wei, Jinlian Hua, Guangpeng Li
Methylation is an important issue in gene expression regulation and also in the fields of genetics and reproduction. In this study, we created fat-1 transgenic sheep, investigated the fine-mapping and the modulatory mechanisms of promoter methylation. Sheep fetal fibroblasts were transfected by pCAG-fat1-IRES-EGFP. Monoclonal cell line was screened as nuclear donor and carried out nuclear transfer (441 transgenic cloned embryos, 52 synchronism recipient sheep). Six offsprings were obtained. Expressions of exogenous genes fat-1 and EGFP were detectable in 10 examined tissues and upregulated omega-3 fatty acid content...
2017: PloS One
https://www.readbyqxmd.com/read/28127428/dna-methyltransferases-and-their-roles-in-tumorigenesis
#14
REVIEW
Wu Zhang, Jie Xu
DNA methylation plays an important role in gene expression, chromatin stability, and genetic imprinting. In mammals, DNA methylation patterns are written and regulated by DNA methyltransferases (DNMTs), including DNMT1, DNMT3A and DNMT3B. Recent emerging evidence shows that defects in DNMTs are involved in tumor transformation and progression, thus indicating that epigenetic disruptions caused by DNMT abnormalities are associated with tumorigenesis. Herein, we review the latest findings related to DNMT alterations in cancer cells and discuss the contributions of these effects to oncogenic phenotypes...
2017: Biomarker Research
https://www.readbyqxmd.com/read/28124145/role-of-oxidative-stress-in-epigenetic-modification-of-mmp-9-promoter-in-the-development-of-diabetic-retinopathy
#15
Renu A Kowluru, Yang Shan
BACKGROUND: In the pathogenesis of diabetic retinopathy, damaged retinal mitochondria accelerate apoptosis of retinal capillary cells, and regulation of oxidative stress by manipulating mitochondrial superoxide dismutase (SOD2) protects mitochondrial homeostasis and prevents the development of diabetic retinopathy. Diabetes also activates matrix metalloproteinase-9 (MMP-9), and activated MMP-9 damages retinal mitochondria. Recent studies have shown a dynamic DNA methylation process playing an important role in regulation of retinal MMP-9 transcription in diabetes; the aim of this study is to investigate the role of oxidative stress in MMP-9 transcription...
May 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28115643/from-the-cover-zinc-oxide-nanoparticles-induced-reactive-oxygen-species-promotes-multimodal-cyto-and-epigenetic-toxicity
#16
Samrat Roy Choudhury, Josue Ordaz, Chiao-Ling Lo, Nur P Damayanti, Feng Zhou, Joseph Irudayaraj
In this study we evaluated and correlated the cytotoxic effects of zinc oxide nanoparticles (ZnO-NPs) to the epigenetic modifications, using human embryonic kidney (HEK-293) cells as a model system. Imaging of singlet and total reactive oxygen species (ROS) in ZnO-NPs-treated live cells was performed followed by the evaluation of its effects on cytoskeletal, mitochondrial, and nuclear integrity, and on the expression of ROS responsive genes. Next, we determined the global and locus-specific changes in DNA-methylation at the 3 global genomic repeat sequences namely LINE-1, subtelomeric D4Z4 and pericentromeric NBL2, and at the promoter of selected ROS responsive genes (AOX1, HMOX1, NCF2, SOD3)...
March 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28110250/detection-and-discrimination-of-maintenance-and-de-novo-cpg-methylation-events-using-methylbreak
#17
William Hsu, Augustus T Mercado, George Hsiao, Jui-Ming Yeh, Chung-Yung Chen
Understanding the principles governing the establishment and maintenance activities of DNA methyltransferases (DNMTs) can help in the development of predictive biomarkers associated with genetic disorders and diseases. A detection system was developed that distinguishes and quantifies methylation events using methylation-sensitive endonucleases and molecular beacon technology. MethylBreak (MB) is a 22-mer oligonucleotide with one hemimethylated and two unmethylated CpG sites, which are also recognition sites for Sau96I and SacII, and is attached to a fluorophore and a quencher...
May 15, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28107650/acetylation-enhances-tet2-function-in-protecting-against-abnormal-dna-methylation-during-oxidative-stress
#18
Yang W Zhang, Zhihong Wang, Wenbing Xie, Yi Cai, Limin Xia, Hariharan Easwaran, Jianjun Luo, Ray-Whay Chiu Yen, Yana Li, Stephen B Baylin
TET proteins, by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are hypothesized, but not directly shown, to protect promoter CpG islands (CGIs) against abnormal DNA methylation (DNAm) in cancer. We define such a protective role linked to DNA damage from oxidative stress (OS) known to induce this abnormality. TET2 removes aberrant DNAm during OS through interacting with DNA methyltransferases (DNMTs) in a "Yin-Yang" complex targeted to chromatin and enhanced by p300 mediated TET2 acetylation...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28107582/immunoexpression-of-hdac1-hdac2-and-hat1-in-actinic-cheilitis-and-lip-squamous-cell-carcinoma
#19
E S Chrun, F Modolo, Dsc Vieira, Áls Borges-Júnior, R G Castro, F I Daniel
BACKGROUND: Acetylation and deacetylation are the most studied covalent histone modifications resulting in transcriptional regulation with histone deacetylases (HDAC) and histone acetyltransferases (HAT) as the main associated enzymes. These enzymes overexpression induces abnormal transcription of key genes that regulate important cellular functions, such as proliferation, cell cycle regulation, and apoptosis. Thus, the expression of different HATs and HDACs has been evaluated in various cancers...
January 20, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28103274/prenatal-exposure-to-lipopolysaccharide-alters-renal-dna-methyltransferase-expression-in-rat-offspring
#20
Jing Wang, Jinghong Cui, Rui Chen, Youcai Deng, Xi Liao, Yanling Wei, Xiaohui Li, Min Su, Jianhua Yu, Ping Yi
Prenatal exposure to inflammation results in hypertension during adulthood but the mechanisms are not well understood. Maternal exposure to lipopolysaccharide (LPS) alters interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in the fetal environment. As reported in many recent studies, IL-6 regulates DNA methyltransferases (DNMTs) through the transcription factor friend leukemia virus integration 1 (Fli-1). The present study explores the role of intrarenal DNMTs during development of hypertension induced by prenatal exposure to LPS...
2017: PloS One
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