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https://www.readbyqxmd.com/read/29033456/the-dna-methyltransferase-family-a-versatile-toolkit-for-epigenetic-regulation
#1
REVIEW
Frank Lyko
The DNA methyltransferase (DNMT) family comprises a conserved set of DNA-modifying enzymes that have a central role in epigenetic gene regulation. Recent studies have shown that the functions of the canonical DNMT enzymes - DNMT1, DNMT3A and DNMT3B - go beyond their traditional roles of establishing and maintaining DNA methylation patterns. This Review analyses how molecular interactions and changes in gene copy numbers modulate the activity of DNMTs in diverse gene regulatory functions, including transcriptional silencing, transcriptional activation and post-transcriptional regulation by DNMT2-dependent tRNA methylation...
October 16, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/29027601/dnmt1-dnmt3a-and-dnmt3b-proteins-are-differently-expressed-in-mouse-oocytes-and-early-embryos
#2
Fatma Uysal, Saffet Ozturk, Gokhan Akkoyunlu
DNA methylation is one of the epigenetic mechanisms and plays important roles during oogenesis and early embryo development in mammals. DNA methylation is basically known as adding a methyl group to the fifth carbon atom of cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinucleotide sites. This mechanism is composed of two main processes: de novo methylation and maintenance methylation, both of which are catalyzed by specific DNA methyltransferase (DNMT) enzymes. To date, six different DNMTs have been characterized in mammals defined as DNMT1, DNMT2, DNMT3A, DNMT3B, DNMT3C, and DNMT3L...
October 13, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29027179/association-of-dnmt3b-283t-c-polymorphism-with-risk-of-lung-and-gastric-cancer-a-case-control-study-and-a-meta-analysis
#3
Xianhong Feng, Jingdong Wang, Xiuli Gu, Jingli Zhang, Xiaolin Li, Zhi Tao, Jiebing Chen, Bifeng Chen
PURPOSE: To investigate the association of DNMT3B -283T>C polymorphism with the risk of lung or gastric cancer, which was followed by a meta-analysis. METHODS: The genotyping of -283T>C was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and was confirmed by sequencing. RESULTS: The results of this case-control study showed that -283T>C was not associated with the risk of lung or gastric cancer, and further stratified analysis according to age, gender, smoking status, and alcohol status confirmed the present finding...
October 12, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/29024060/loss-of-dnmt3b-in-chondrocytes-leads-to-delayed-endochondral-ossification-and-fracture-repair
#4
Cuicui Wang, Yousef Abu-Amer, Regis J O'Keefe, Jie Shen
Despite advanced understanding of signaling mediated by local and systemic factors, the role of epigenetic factors in the regulation of bone regeneration remains vague. The DNA methyltransferases (Dnmts) Dnmt3a and Dnmt3b have tissue specific expression patterns and create unique methylation signatures to regulate gene expression. Using a stabilized murine tibia fracture model we find that Dnmt3b is induced early in fracture healing, peaks at 10 days post fracture (dpf), and declines to nearly undetectable levels by 28 dpf...
October 10, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28990350/association-of-dnmt3b-gene-variants-with-sporadic-parkinson-s-disease-in-a-chinese-han-population
#5
Xiang Chen, Yousheng Xiao, Lei Wei, Yijuan Wu, Jianjun Lu, Wenyuan Guo, Shuxuan Huang, Miaomiao Zhou, Mingshu Mo, Zhe Li, Luan Cen, Shaomin Li, ChaohaoYang, Zhuohua Wu, Sophie Hu, Zhong Pei, XinLing Yang, Shaogang Qu, Pingyi Xu
INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Epigenetic modifications, specifically DNA methylation, have been implicated in the development of this disease. Genetic variants of DNA methyltransferase 3b (DNMT3b), one of the most important DNA methyltransferases, were shown to be associated with PD in a Brazilian population. However, it is unclear whether genetic variants of DNMT3b increase the risk of PD in the Chinese Han people...
October 9, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28979331/study-of-the-role-of-sirna-mediated-promoter-methylation-in-dnmt3b-knockdown-and-alteration-of-promoter-methylation-of-cdh1-gstp1-genes-in-mda-mb-453-cell-line
#6
Mojgan Naghitorabi, Hamid Mir Mohammad Sadeghi, Javad Mohammadi Asl, Mohammad Rabbani, Abbas Jafarian-Dehkordi
Promoter methylation is one of the main epigenetic mechanisms that leads to the inactivation of tumor suppressor genes during carcinogenesis. Due to the reversible nature of DNA methylation, many studies have been performed to correct theses epigenetic defects by inhibiting DNA methyltransferases (DNMTs). In this case novel therapeutics especially siRNA oligonucleotides have been used to specifically knock down the DNMTs at mRNA level. Also many studies have focused on transcriptional gene silencing in mammalian cells via siRNA mediated promoter methylation...
2017: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/28973513/non-random-length-distribution-of-individual-telomeres-in-immunodeficiency-centromeric-instability-and-facial-anomalies-syndrome-type-i
#7
Shira Sagie, Omer Edni, Joseph Weinberg, Shir Toubiana, Tal Kozlovski, Tzviel Frostig, Nirit Katzin, Irit Bar-Am, Sara Selig
Mutations in the de novo DNA methyltransferase DNMT3B lead to Immunodeficiency, Centromeric Instability and Facial anomalies (ICF) syndrome, type I. This syndrome is characterized, among other hypomethylated genomic loci, by severe subtelomeric hypomethylation that is associated with abnormally short telomere length. While it was demonstrated that the mean telomere length is significantly shorter in ICF type I cells, it is unknown whether all telomeres are equally vulnerable to shortening. To study this question we determined by combined telomere-FISH and spectral karyotyping the relative length of each individual telomere in lymphoblastoid cell lines (LCLs) generated from multiple ICF syndrome patients and control individuals...
August 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28972577/genome-wide-association-study-across-european-and-african-american-ancestries-identifies-a-snp-in-dnmt3b-contributing-to-nicotine-dependence
#8
D B Hancock, Y Guo, G W Reginsson, N C Gaddis, S M Lutz, R Sherva, A Loukola, C C Minica, C A Markunas, Y Han, K A Young, D F Gudbjartsson, F Gu, D W McNeil, B Qaiser, C Glasheen, S Olson, M T Landi, P A F Madden, L A Farrer, J Vink, N L Saccone, M C Neale, H R Kranzler, J McKay, R J Hung, C I Amos, M L Marazita, D I Boomsma, T B Baker, J Gelernter, J Kaprio, N E Caporaso, T E Thorgeirsson, J E Hokanson, L J Bierut, K Stefansson, E O Johnson
Cigarette smoking is a leading cause of preventable mortality worldwide. Nicotine dependence, which reduces the likelihood of quitting smoking, is a heritable trait with firmly established associations with sequence variants in nicotine acetylcholine receptor genes and at other loci. To search for additional loci, we conducted a genome-wide association study (GWAS) meta-analysis of nicotine dependence, totaling 38,602 smokers (28,677 Europeans/European Americans and 9925 African Americans) across 15 studies...
October 3, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28971377/microrna-expression-profiling-in-alveolar-macrophages-of-indigenous-chinese-tongcheng-pigs-infected-with-prrsv-in-vivo
#9
Xiang Zhou, Jennifer J Michal, Zhihua Jiang, Bang Liu
Porcine respiratory and reproductive syndrome (PRRS), caused by PRRS virus (PRRSV), is one of the most serious infectious diseases in the swine industry worldwide. Indigenous Chinese Tongcheng (TC) pigs reportedly show strong resistance to PRRSV infection. The miRNA expression profiles of porcine alveolar macrophages (PAMs) of control TC pigs and those infected with PRRSV in vivo were analyzed by high-throughput sequencing to explore changes induced by infection. A total of 182 known miRNAs including 101 miRNA-5p and 81 miRNA-3p were identified with 23 up-regulated differentially expressed miRNAs (DEmiRNAs) and 25 down-regulated DEmiRNAs...
October 2, 2017: Journal of Applied Genetics
https://www.readbyqxmd.com/read/28965139/epigenetic-changes-in-preimplantation-embryos-subjected-to-laser-manipulation
#10
Sachin D Honguntikar, Sujith Raj Salian, Fiona D'Souza, Shubhashree Uppangala, Guruprasad Kalthur, Satish Kumar Adiga
The advantage of using laser for assisted hatching in routine assisted reproductive technology (ART) practice is debatable. Recently, it has been shown that laser-manipulated mouse embryos had compromised genetic integrity. However, the impact of laser-assisted hatching (LAH) on the epigenetic integrity of the preimplantation embryos is not elucidated so far. Since continuous thermal stress on embryos was found to lower mRNA levels of de novo (bovine) methyl transferases in embryos, we hypothesize that thermal energy induced during LAH may alter the epigenetic signature through abnormal de novo methyl transferases (Dnmts) levels...
September 30, 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/28963472/zfp296-negatively-regulates-h3k9-methylation-in-embryonic-development-as-a-component-of-heterochromatin
#11
Takumi Matsuura, Satsuki Miyazaki, Tatsushi Miyazaki, Fumi Tashiro, Jun-Ichi Miyazaki
The Cys2/His2-type zinc finger protein Zfp296 has been implicated in stem cell pluripotency and tumor pathogenesis. However, its mechanisms remain elusive. Here, we demonstrated that a Zfp296 deficiency in mice impairs germ-cell development and embryonic growth. Zfp296 was intracellularly localized to heterochromatin in embryos. A GST-Zfp296 pull-down experiment using ES cell nuclear extract followed by LC-MS/MS showed that Zfp296 interacts with component proteins of heterochromatin (such as HP1, Dnmt1, Dnmt3b, and ATRX) and the NuRD complex...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28958182/epigenetic-changes-in-the-early-stage-of-silica-induced-cell-transformation
#12
Carole Seidel, Anaïs Kirsch, Caroline Fontana, Athanase Visvikis, Aurélie Remy, Laurent Gaté, Christian Darne, Yves Guichard
The increasing use of nanomaterials in numerous domains has led to growing concern about their potential toxicological properties, and the potential risk to human health posed by silica nanoparticles remains under debate. Recent studies proposed that these particles could alter gene expression through the modulation of epigenetic marks, and the possible relationship between particle exposure and these mechanisms could represent a critical factor in carcinogenicity. In this study, using the Bhas 42 cell model, we compare the effects of exposure to two transforming particles, a pyrogenic amorphous silica nanoparticle NM-203 to those of the crystalline silica particle Min-U-Sil(®) 5...
September 28, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28945286/do-mutations-in-dnmt3a-3b-affect-global-dna-hypomethylation-among-benzene-exposed-workers-in-southeast-china-effects-of-mutations-in-dnmt3a-3b-on-global-dna-hypomethylation
#13
Guang-Hui Zhang, Ye Lu, Bu-Qiang Ji, Jing-Chao Ren, Pin Sun, Shibin Ding, Xiaoling Liao, Kaiju Liao, Jinyi Liu, Jia Cao, Qing Lan, Nathaniel Rothman, Zhao-Lin Xia
Global DNA hypomethylation is commonly observed in benzene-exposed workers, but the underlying mechanisms remain unclear. We sought to discover the relationships among reduced white blood cell (WBC) counts, micronuclear (MN) frequency, and global DNA methylation to determine whether there were associations with mutations in DNMT3A/3B. Therefore, we recruited 410 shoe factory workers and 102 controls from Wenzhou in Zhenjiang Province. A Methylated DNA Quantification Kit was used to quantify global DNA methylation, and single nucleotide polymorphisms (SNPs) in DNMT3A (rs36012910, rs1550117, and R882) and DNMT3B (rs1569686, rs2424909, and rs2424913) were identified using the restriction fragment length polymorphism method...
September 25, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28940947/a-single-nucleotide-polymorphism-of-dna-methyltransferase-3b-gene-is-a-risk-factor-for-recurrent-spontaneous-abortion
#14
Anita Barišić, Nina Pereza, Alenka Hodžić, Saša Ostojić, Borut Peterlin
PROBLEM: Aberrant DNA methylation has been suggested as a potential cause of recurrent spontaneous abortion (RSA). Considering the growing evidence on the important roles of DNA methylation in gametogenesis and early pregnancy, we investigated the potential association of DNA methyltransferase gene polymorphisms (DNMT1 rs2228611, DNMT3A rs1550117, DNMT3B rs1569686) with RSA in Slovenian reproductive couples. METHOD OF STUDY: A total of 146 couples with ≥3 consecutive spontaneous abortions and 149 control women and men with ≥2 normal pregnancies were included...
September 20, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28939082/epigenetic-therapy-regulates-the-expression-of-aldh1-and-immunologic-response-relevance-to-the-prognosis-of-oral-cancer
#15
Ming-Shao Tsai, Wen-Cheng Chen, Chia-Hsuan Lai, Yu-Yen Chen, Miao-Fen Chen
OBJECTIVES: Aldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and shown to identify cancer stem cells (CSC)-like cells. We aimed to investigate the significance of ALDH1 in oral squamous cell carcinoma (OSCC) and its correlation with DNMT3b and immune evasion in the present study. METHODS: We retrospectively analyzed the clinical outcomes of OSCC patients and examined its correlation with the levels of ALDH1 in tumors and circulating myeloid-derived suppressor cells (MDSCs) in the peripheral blood...
October 2017: Oral Oncology
https://www.readbyqxmd.com/read/28912888/sulforaphane-induced-cell-cycle-arrest-and-senescence-are-accompanied-by-dna-hypomethylation-and-changes-in-microrna-profile-in-breast-cancer-cells
#16
Anna Lewinska, Jagoda Adamczyk-Grochala, Anna Deregowska, Maciej Wnuk
Cancer cells are characterized by genetic and epigenetic alterations and phytochemicals, epigenetic modulators, are considered as promising candidates for epigenetic therapy of cancer. In the present study, we have investigated cancer cell fates upon stimulation of breast cancer cells (MCF-7, MDA-MB-231, SK-BR-3) with low doses of sulforaphane (SFN), an isothiocyanate. SFN (5-10 µM) promoted cell cycle arrest, elevation in the levels of p21 and p27 and cellular senescence, whereas at the concentration of 20 µM, apoptosis was induced...
2017: Theranostics
https://www.readbyqxmd.com/read/28900200/differential-landscape-of-non-cpg-methylation-in-embryonic-stem-cells-and-neurons-caused-by-dnmt3s
#17
Jong-Hun Lee, Sung-Joon Park, Kenta Nakai
Methylated non-CpGs (mCpH; H means A, C, and T) have emerged as key epigenetic marks in mammalian embryonic stem cells (ESCs) and neurons, regulating cell type-specific functions. In these two cell types, mCpHs show distinct motifs and correlations to transcription that could be a key in understanding the cell type-specific regulations. Thus, we attempted to uncover the underlying mechanism of the differences in ESCs and neurons by conducting a comprehensive analysis of public whole genome bisulfite sequencing data...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28894282/idiopathic-male-infertility-and-polymorphisms-in-the-dna-methyltransferase-genes-involved-in-epigenetic-marking
#18
Qiuqin Tang, Yiqiu Chen, Wei Wu, Hongjuan Ding, Yankai Xia, Daozhen Chen, Xinru Wang
The purpose of this study was to investigate the association between male infertility and single-nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMT) genes (DNMT3B: rs2424909, DNMT1: rs4804490, DNMT3A: rs1550117 and DNMT3L: rs7354779). Eight hundred and thirty three idiopathic infertile males and four hundred and ten fertile controls from the hospitals affiliated to Nanjing Medical University between 2010 and 2012 were recruited in the study. We demonstrated a significantly increased risk of idiopathic infertility with abnormal semen parameters in association with the heterozygous genotype of variant rs4804490...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28892045/mn1-overexpression-is-driven-by-loss-of-dnmt3b-methylation-activity-in-inv-16-pediatric-aml
#19
N S D Larmonie, T C J M Arentsen-Peters, A Obulkasim, D Valerio, E Sonneveld, A A Danen-van Oorschot, V de Haas, D Reinhardt, M Zimmermann, J Trka, A Baruchel, R Pieters, M M van den Heuvel-Eibrink, C M Zwaan, M Fornerod
In acute myeloid leukemia (AML), specific genomic aberrations induce aberrant methylation, thus directly influencing the transcriptional programing of leukemic cells. Therefore, therapies targeting epigenetic processes are advocated as a promising therapeutic tool for AML treatment. However, to develop new therapies, a comprehensive understanding of the mechanism(s) driving the epigenetic changes as a result of acquired genetic abnormalities is necessary. This understanding is still lacking. In this study, we performed genome-wide CpG-island methylation profiling on pediatric AML samples...
September 11, 2017: Oncogene
https://www.readbyqxmd.com/read/28891753/the-influence-of-schisandrin-b-on-a-model-of-alzheimer-s-disease-using-%C3%AE-amyloid-protein-a%C3%AE-1-42-mediated-damage-in-sh-sy5y-neuronal-cell-line-and-underlying-mechanisms
#20
Ming Zhang, Hong-Xia Zheng, Yang-Yang Gao, Bo Zheng, Jing-Ping Liu, He Wang, Zhan-Jun Yang, Zhi-Ying Zhao
Schisandrin B, an active substance, is derived from Chinese herb fruit Wuweizi, which exerts various pharmacological activities and has displayed significant beneficial effects in ameliorating Alzheimer's disease (AD). The aim of this study was to further extend our examination for the use of schisandrin B extract in the potential treatment of AD effects by investigating DNA methylation (DNMT), known to be modified in this disease using SH-SY5Y neuronal cell line exposed to β-amyloid protein (Aβ1-42). In particular, the purpose of this investigation was to examine alterations in mRNA and protein expression of DNMT...
September 11, 2017: Journal of Toxicology and Environmental Health. Part A
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