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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
#1
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
#2
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
#3
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...
January 25, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28115643/zno-nanoparticles-induced-reactive-oxygen-species-promotes-multimodal-cyto-and-epigenetic-toxicity
#4
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 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 three genomic repeat sequences namely global LINE-1, subtelomeric D4Z4 and pericentromeric NBL2, and at the promoter of selected ROS responsive genes (AOX1, HMOX1, NCF2, SOD3)...
January 22, 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
#5
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
#6
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
#7
Emanuely da Silva Chrun, Filipe Modolo, Daniella Serafim Couto Vieira, Álvaro Luiz Socorro Borges, Renata Goulart Castro, Filipe Ivan Daniel
BACKGROUND: Acetylation/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
#8
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
https://www.readbyqxmd.com/read/28102109/epigenetic-regulation-of-rgs2-regulator-of-g-protein-signaling-2-in-chemoresistant-ovarian-cancer-cells
#9
Ercan Cacan
Regulator of G-protein signaling 2 (RGS2) is a GTPase-activating protein functioning as an inhibitor of G-protein coupled receptors (GPCRs). RGS2 dysregulation was implicated in solid tumour development and RGS2 downregulation has been reported in prostate and ovarian cancer progression. However, the molecular mechanism by which RGS2 expression is suppressed in ovarian cancer remains unknown. The expression and epigenetic regulation of RGS2 in chemosensitive and chemoresistant ovarian cancer cells were determined by qRT-PCR and chromatin immunoprecipitation assays, respectively...
January 19, 2017: Journal of Chemotherapy
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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...
March 1, 2017: 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
#16
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
#17
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
#18
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
#19
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
#20
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
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