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Dnmt3a

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https://www.readbyqxmd.com/read/29031013/intragenic-hypomethylation-of-dnmt3a-in-patients-with-myelodysplastic-syndrome
#1
Ying-Ying Zhang, Jing-Dong Zhou, Dong-Qin Yang, Pin-Fang He, Dong-Ming Yao, Zhen Qian, Jing Yang, Wen-Rong Xu, Jiang Lin, Jun Qian
BACKGROUND: DNMT3A is a DNA methyltransferase that acts in de novo methylation. Aberrant expression of DNMT3A has been reported in several human diseases, including myelodysplastic syndrome (MDS). However, the pattern of DNMT3A methylation remains unknown in MDS. METHODS: The present study was aimed to investigate the methylation status of DNMT3A intragenic differentially methylated region 2 (DMR2) using real-time quantitative methylation-specific PCR and analyze its clinical significance in MDS...
October 14, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29028111/dna-methylation-of-methylation-complex-genes-in-relation-to-stress-and-genome-wide-methylation-in-mother-newborn-dyads
#2
Christopher J Clukay, David A Hughes, Nicole C Rodney, Darlene A Kertes, Connie J Mulligan
OBJECTIVES: Early life stress is known to have enduring biological effects, particularly with respect to health. Epigenetic modifications, such as DNA methylation, are a possible mechanism to mediate the biological effect of stress. We previously found correlations between maternal stress, newborn birthweight, and genome-wide measures of DNA methylation. Here we investigate ten genes related to the methylation/demethylation complex in order to better understand the impact of stress on health...
October 13, 2017: American Journal of Physical Anthropology
https://www.readbyqxmd.com/read/29027601/dnmt1-dnmt3a-and-dnmt3b-proteins-are-differently-expressed-in-mouse-oocytes-and-early-embryos
#3
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/29024790/dna-methylation-and-potential-multigenerational-epigenetic-effects-linked-to-uranium-chronic-low-dose-exposure-in-gonads-of-males-and-females-rats
#4
REVIEW
G Elmhiri, C Gloaguen, S Grison, D Kereselidze, C Elie, K Tack, M Benderitter, P Lestaevel, A Legendre, M Souidi
INTRODUCTION: An increased health problem in industrialised countries is the contemporary concern of public and scientific community as well. This has been attributed in part to accumulated environmental pollutants especially radioactive substances and the use of nuclear power plants worldwide. However, the outcome of chronic exposure to low doses of a radionuclide such as uranium remains unknown. Recently, a paradigm shift in the perception of risk of radiotoxicology has emerged through investigating the possibility of transmission of biological effects over generations, in particular by epigenetic pathways...
October 9, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29024628/biologico-clinical-significance-of-dnmt3a-variants-expression-in-acute-myeloid-leukemia
#5
Na Lin, Wei Fu, Chen Zhao, Bixin Li, Xiaojing Yan, Yan Li
DNA methyltransferase 3A (DNMT3A) catalyzes de novo DNA methylation and plays important roles in the pathogenesis of acute myeloid leukemia. However, the expression status of DNMT3A variants in acute myeloid leukemia remains obscure. This study aimed to assess the expression levels of alternative splicing of DNMT3A variants and explore their roles in acute myeloid leukemia (AML). DNMT3A variants gene expression were assessed, measuring their effects on cell proliferation. In addition, the expression of DNMT3A variants were evaluated in acute myeloid leukemia patients...
October 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29024060/loss-of-dnmt3b-in-chondrocytes-leads-to-delayed-endochondral-ossification-and-fracture-repair
#6
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/28992762/mutations-in-tet2-and-dnmt3a-genes-are-associated-with-changes-in-global-and-gene-specific-methylation-in-acute-myeloid-leukemia
#7
Alberto Ponciano-Gómez, Adolfo Martínez-Tovar, Jorge Vela-Ojeda, Irma Olarte-Carrillo, Federico Centeno-Cruz, Efraín Garrido
Acute myeloid leukemia is characterized by its high biological and clinical heterogeneity, which represents an important barrier for a precise disease classification and accurate therapy. While epigenetic aberrations play a pivotal role in acute myeloid leukemia pathophysiology, molecular signatures such as change in the DNA methylation patterns and genetic mutations in enzymes needed to the methylation process can also be helpful for classifying acute myeloid leukemia. Our study aims to unveil the relevance of DNMT3A and TET2 genes in global and specific methylation patterns in acute myeloid leukemia...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28990703/effects-of-maternal-separation-and-antidepressant-drug-on-epigenetic-regulation-of-the-bdnf-exon-i-promoter-in-the-adult-rat-hippocampus
#8
Mi Kyoung Seo, Jung Goo Lee, Le Thi Hien, Sung Woo Park, Young Hoon Kim
AIM: Early life stress can induce epigenetic changes through genetic and environmental interactions and is a risk factor for depression. Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression and antidepressant drug action. We investigated epigenetic changes at the BDNF exon I promoter in the hippocampus of adult rats subjected to maternal separation (MS) during early life and treated with an antidepressant drug as adults. METHODS: Rat pups were subjected to MS from postnatal day 1 to 21 and received chronic escitalopram (ESC) as adults...
October 9, 2017: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/28978861/acute-leukemia-in-adolescents-and-young-adults
#9
Daisuke Tomizawa
Both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are common malignant diseases in adolescents and young adults (AYAs). Recent advances in genomic studies have helped us understand the biological nature of acute leukemia in AYAs; higher frequency of Ph-like ALL and rearrangements in DUX4, ERG, MEF2D, and ZNF384 genes in AYAs with ALL and higher frequency of FLT3-ITD, NPM1, IDH1/2, DNMT3A, ASXL1, TET2, and CEBPA mutations in AYAs with AML than that in children. The pediatric-inspired regimen has become a standard treatment approach for AYAs with ALL, but optimal treatment strategy for AYAs with AML is not yet established to date...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978821/sequential-acquisition-of-mutations-in-myelodysplastic-syndromes
#10
Hideki Makishima
Recent progress in next-generation sequencing technologies allows us to discover frequent mutations throughout the coding regions of myelodysplastic syndromes (MDS), potentially providing us with virtually a complete spectrum of driver mutations in this disease. As shown by many study groups these days, such driver mutations are acquired in a gene-specific fashion. For instance, DDX41 mutations are observed in germline cells long before MDS presentation. In blood samples from healthy elderly individuals, somatic DNMT3A and TET2 mutations are detected as age-related clonal hematopoiesis and are believed to be a risk factor for hematological neoplasms...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978819/epigenetic-dysregulation-in-myelodysplastic-syndromes
#11
Goro Sashida
Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease characterized by impaired hematopoiesis and an increased risk of transformation to acute myeloid leukemia (AML). Epigenetic regulators, including TET2, DNMT3A and EZH2, are often mutated in patients with MDS. Recently, exome sequencing of blood cells from aged people without hematological malignancies have demonstrated the presence of clonal hematopoiesis with myeloid malignancies-associated mutations, such as TET2 and DNMT3A. Here, I will discuss the molecular mechanisms underlying the accumulation of epigenetic alterations and genetic mutations, including TET2, DNMT3A and EZH2, and how these promote the development of MDS and hematological malignancies in aged people with clonal hematopoiesis...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978469/prostaglandin-e2-leads-to-the-acquisition-of-dnmt3a-dependent-tolerogenic-functions-in-human-myeloid-derived-suppressor-cells
#12
Javier Rodríguez-Ubreva, Francesc Català-Moll, Nataša Obermajer, Damiana Álvarez-Errico, Ricardo N Ramirez, Carlos Company, Roser Vento-Tormo, Gema Moreno-Bueno, Robert P Edwards, Ali Mortazavi, Pawel Kalinski, Esteban Ballestar
Myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs) arise from common progenitors. Tumor-derived factors redirect differentiation from immune-promoting DCs to tolerogenic MDSCs, an immunological hallmark of cancer. Indeed, in vitro differentiation of DCs from human primary monocytes results in the generation of MDSCs under tumor-associated conditions (PGE2 or tumor cell-conditioned media). Comparison of MDSC and DC DNA methylomes now reveals extensive demethylation with specific gains of DNA methylation and repression of immunogenic-associated genes occurring in MDSCs specifically, concomitant with increased DNA methyltransferase 3A (DNMT3A) levels...
October 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28973434/dcas9-based-epigenome-editing-suggests-acquisition-of-histone-methylation-is-not-sufficient-for-target-gene-repression
#13
Henriette O'Geen, Chonghua Ren, Charles M Nicolet, Andrew A Perez, Julian Halmai, Victoria M Le, Joel P Mackay, Peggy J Farnham, David J Segal
Distinct epigenomic profiles of histone marks have been associated with gene expression, but questions regarding the causal relationship remain. Here we investigated the activity of a broad collection of genomically targeted epigenetic regulators that could write epigenetic marks associated with a repressed chromatin state (G9A, SUV39H1, Krüppel-associated box (KRAB), DNMT3A as well as the first targetable versions of Ezh2 and Friend of GATA-1 (FOG1)). dCas9 fusions produced target gene repression over a range of 0- to 10-fold that varied by locus and cell type...
September 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28972040/downregulation-of-dnmt3a-by-mir-708-5p-inhibits-lung-cancer-stem-cell-like-phenotypes-through-repressing-wnt-%C3%AE-catenin-signaling
#14
Xiaohua Hu, Tianchi Liu, Xiaoping Wu, Tong Chen, Zewei Luo
PURPOSE: Lung cancer is the leading cause of cancer death in the world, and emerging evidences suggest that lung cancer stem cells (CSCs) are associated with its poor prognosis, tumor recurrence and therapy resistance. Here we reveal a novel role for miR-708-5p in inhibiting lung cancer stem cell-like features. EXPERIMENTAL DESIGN: Phenotypic effects of miR-708-5p on the lung CSC-like properties were examined by in vitro sphere formation assay and in xenografted animal models...
September 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28965139/epigenetic-changes-in-preimplantation-embryos-subjected-to-laser-manipulation
#15
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/28964959/genetic-variations-of-bone-marrow-mesenchymal-stromal-cells-derived-from-acute-leukemia-and-myelodysplastic-syndrome-by-targeted-deep-sequencing
#16
Kenko Azuma, Tomohiro Umezu, Satoshi Imanishi, Michiyo Asano, Seiichiro Yoshizawa, Seiichiro Katagiri, Kazuma Ohyashiki, Junko H Ohyashiki
Bone marrow mesenchymal stromal cells (MSCs), which support proliferation and differentiation of hematopoietic stem cells, may play a crucial role in the pathogenesis of myeloid neoplasms. To determine whether MSCs in myeloid neoplasms harbor distinct somatic mutations that may affect their function, we used a targeted gene sequencing panel containing 50 myeloid neoplasm-associated genes with coverage of ≥500. We compared the genetic alterations between MSCs and bone marrow hematopoietic (BM) cells from patients with acute leukemia (n=5) or myelodysplastic syndrome (MDS, n=5)...
September 21, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28964809/continuous-soy-isoflavones-exposure-from-weaning-to-maturity-induces-downregulation-of-ovarian-steroidogenic-factor-1-gene-expression-and-corresponding-changes-in-dna-methylation-pattern
#17
Wenxiang Wang, Yan Sun, Yiwei Guo, Ping Cai, Yuchen Li, Jin Liu, Guoxi Cai, Aoyagi Kiyoshi, Wenchang Zhang
Female Wistar rats were treated with orally administered soy isoflavones at concentrations of 0, 25, 50, or 100mg/kg body weight from weaning until sexual maturity (3 mo.), and ovarian steroidogenesis was evaluated. After soy isoflavones were administered, a significant (P<0.05) decrease (44%) in the serum estrodial levels of the high-dose (HD) group were observed. Cultured granulosa cells from the middle- (MD) and HD groups showed significantly (P<0.05) reduced (31%, 45%, respectively) in vitro estradiol secretion, and those from the HD group showed significantly (P<0...
September 27, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28960408/residual-disease-detection-using-targeted-parallel-sequencing-predicts-relapse-in-cytogenetically-normal-acute-myeloid-leukemia
#18
Lukas Gaksch, Karl Kashofer, Ellen Heitzer, Franz Quehenberger, Shruti Daga, Sybille Hofer, Iris Halbwedl, Ricarda Graf, Nina Krisper, Gerald Hoefler, Armin Zebisch, Heinz Sill, Albert Wölfler
Despite achieving complete remission after intensive therapy, most patients with cytogenetically normal (CN) AML relapse due to the persistence of submicroscopic residual disease. In this pilot study, we hypothesized that detection of leukemia-specific mutations following consolidation treatment using a targeted parallel sequencing approach predicts relapse. We included 34 AML patients of whom diagnostic material and remission bone marrow slides after at least one cycle of consolidation were available. Isolated DNA was screened for mutations in 19 genes using an Ion Torrent sequencing platform...
September 29, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28960206/mir-148a-inhibits-colitis-and-colitis-associated-tumorigenesis-in-mice
#19
Yahui Zhu, Li Gu, Yajun Li, Xi Lin, Hongxing Shen, Kaisa Cui, Li Chen, Feng Zhou, Qiu Zhao, Jinxiang Zhang, Bo Zhong, Edward Prochownik, Youjun Li
miR-148a has been shown to regulate inflammation, immunity and the growth of certain tumors, but its roles in colitis and colorectal tumorigenesis remain largely undetermined. Here we found miR-148a-deficient mice to be more susceptible to colitis and colitis-associated tumorigenesis. Both were associated with increased nuclear factor κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) signaling. Bone marrow- and non-bone marrow-derived miR-148a contributed to colitis and colitis-associated tumorigenesis...
September 29, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28958182/epigenetic-changes-in-the-early-stage-of-silica-induced-cell-transformation
#20
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
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