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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/29024790/dna-methylation-and-potential-multigenerational-epigenetic-effects-linked-to-uranium-chronic-low-dose-exposure-in-gonads-of-males-and-females-rats
#3
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/28993705/a-vicious-loop-of-fatty-acid-binding-protein-4-and-dna-methyltransferase-1-promotes-acute-myeloid-leukemia-and-acts-as-a-therapeutic-target
#4
F Yan, N Shen, J X Pang, N Zhao, Y W Zhang, A M Bode, A Al-Kali, M R Litzow, B Li, S J Liu
Aberrant DNA methylation mediated by deregulation of DNA methyltransferases (DNMT) is a key hallmark of acute myeloid leukemia (AML), yet efforts to target DNMT deregulation for drug development have lagged. We previously demonstrated that upregulation of fatty acid-binding protein 4 (FABP4) promotes AML aggressiveness through enhanced DNMT1-dependent DNA methylation. Here we demonstrate that FABP4 upregulation in AML cells occurs through vascular endothelial growth factor (VEGF) signaling, thus elucidating a crucial FABP4-DNMT1 regulatory feedback loop in AML biology...
October 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28971773/development-potential-anticancer-activity-and-the-receptor-profile-of-different-functionalized-1-3-5-triazine-derivatives
#5
Mona O Sarhan, Mohamed A Motaleb, Ismail T Ibrahim, Wafaa A Zaghary, Manal M Anwar
1,3,5-Triazine-based compounds form a privileged class of compounds in the medicinal chemistry field as they are versatile synthetic scaffolds possessing wide spectra of biological effects including potential anticancer activity. 1,3,5-Triazine compounds explored for anticancer activities have been reported to act by various mechanisms on several molecular targets in human cells such as methyltransferase (DNMT), heat shock protein 90 (Hsp90) and phosphoinositide 3-kinase (PI3K). This review focuses on the synthetic strategies for current developments of 1,3,5-triazine-based anticancer agents and discuses the docking studies that confirm their unique binding modes in the targeted receptors active sites...
September 27, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28969601/genome-wide-analysis-of-dna-methylation-profiles-on-sheep-ovaries-associated-with-prolificacy-using-whole-genome-bisulfite-sequencing
#6
Yanli Zhang, Fengzhe Li, Xu Feng, Hua Yang, Aoxiang Zhu, Jing Pang, Le Han, Tingting Zhang, Xiaolei Yao, Feng Wang
BACKGROUND: Ovulation rate and litter size are important reproductive traits in sheep with high economic value. Recent work has revealed a potential link between DNA methylation and prolificacy. However, a genome-wide study that sought to identify potential DNA methylation sites involved in sheep prolificacy indicated that it is still unknown. Here, we aimed to investigate the genome-wide DNA methylation profiles of Hu sheep ovaries by comparing a high-prolificacy group (HP, litter size of three for at least 2 consecutive lambings) and low prolificacy group (LP, litter size of one for at least 2 consecutive lambings) using deep whole-genome bisulfite sequencing (WGBS)...
October 2, 2017: BMC Genomics
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
#7
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/28954936/different-schedule-dependent-effects-of-epigenetic-modifiers-on-cytotoxicity-by-anticancer-drugs-in-colorectal-cancer-cells
#8
Mika Hosokawa, Shota Tanaka, Kumiko Ueda, Seigo Iwakawa
Limited information is currently available on how to apply epigenetic modifiers to current colorectal cancer (CRC) chemotherapy. The purpose of this study is to clarify the schedule-dependent effects of combined treatment with conventional anticancer drugs and epigenetic modifiers in human CRC cells. Cytotoxicity in 4 CRC cell lines (SW480, HT29, SW48, and HCT116) was measured using the WST-8 assay. As epigenetic modifiers, 3 DNA methyltransferase (DNMT) inhibitors such as decitabine (DAC), azacytidine (AC), and zebularine (Zeb), and 3 histone deacetylase (HDAC) inhibitors including trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), and valproic acid (VPA) were used...
September 28, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28938637/the-loss-of-function-of-dna-methyltransferase-1-by-sirna-impairs-the-growth-of-non-small-cell-lung-cancer-with-alleviated-side-effects-via-reactivation-of-rassf1a-and-apc-in-vitro-and-vivo
#9
Qi Lai, Yin-Hui Xu, Qiang Chen, Liang Tang, An-Gui Li, Li-Fei Zhang, Chun-Fang Zhang, Jian-Fei Song, Zhen-Zong Du
Hypermethylation of tumor suppressor genes (TSGs) promoters by DNA methyltransferase (DNMT) can be observed in almost all cancers which represent a hallmark of carcinogenesis, including lung cancer. DNMT inhibitors (e.g.5-Aza-CR/CdR) reactivate TSGs to exert anti-cancer activity and have been applied into the clinical. However, it is cytotoxic even at low concentrations, which might be not directly related to DNA methylation. We here investigated an alternative strategy in the lung cancer therapy and aimed to estimate and compare its efficiency and side effects of knockdown of DNMT1 in vitro and in vivo...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28934503/a-novel-requirement-for-drosha-in-maintenance-of-mammalian-cg-methylation
#10
Athanasia Stathopoulou, Jyoti B Chhetri, John C Ambrose, Pierre-Olivier Estève, Lexiang Ji, Hediye Erdjument-Bromage, Guoqiang Zhang, Thomas A Neubert, Sriharsa Pradhan, Javier Herrero, Robert J Schmitz, Steen K T Ooi
In mammals, faithful inheritance of genomic methylation patterns ensures proper gene regulation and cell behaviour, impacting normal development and fertility. Following establishment, genomic methylation patterns are transmitted through S-phase by the maintenance methyltransferase Dnmt1. Using a protein interaction screen, we identify Microprocessor component DROSHA as a novel DNMT1-interactor. Drosha-deficient embryonic stem (ES) cells display genomic hypomethylation that is not accounted for by changes in the levels of DNMT proteins...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28925878/genistein-induces-alterations-of-epigenetic-modulatory-signatures-in-human-cervical-cancer-cells
#11
Madhumitha Kedhari Sundaram, Mohammad Zeeshan Ansari, Abdullah Al Mutery, Maryam Ashraf, Reem Nasab, Sheethal Rai, Naushad Rais, Arif Hussain
Introduction Epidemiological studies indicate that diet rich in fruits and vegetables are associated with decreased cancer risk thereby indicating that dietary polyphenols can be potential chemo-preventive agents. The reversible nature of epigenetic modifications makes them a favorable target for cancer prevention. Polyphenols have been shown to reverse aberrant epigenetic patterns by targeting the regulatory enzymes, DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). In vitro and in silico studies of DNMTs and HDACs were planned to examine genistein's role as a natural epigenetic modifier in human cervical cancer cells, HeLa...
September 18, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28903350/zeb1-confers-stem-cell-like-properties-in-breast-cancer-by-targeting-neurogenin-3
#12
Chen Zhou, Huimin Jiang, Zhen Zhang, Guomin Zhang, Hang Wang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Shuang Yang
Cancer stem cells (CSCs) are a subpopulation of cancer cells believed to be implicated in cancer initiation, progression, and recurrence. Here, we report that ectopic expression of zinc finger E-box binding homeobox 1 protein (ZEB1) results in the acquisition of CSC properties by breast cancer cells, leading to tumor initiation and progression in vitro and in vivo. The neurogenin 3 gene (Ngn3) is a bona fide target of ZEB1, and its repression is a key factor contributing to ZEB1-induced cancer cell stemness...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901456/the-antitumor-effects-of-arsenic-trioxide-in-mantle-cell-lymphoma-via-targeting-wnt-%C3%AE-%C3%A2-catenin-pathway-and-dna-methyltransferase-1
#13
Xin-Yu Li, Ying Li, Lingyan Zhang, Xin Liu, Lili Feng, Xin Wang
Mantle cell lymphoma (MCL) is an aggressive non‑Hodgkin lymphoma (NHL) with poor prognosis. The rapid progression and frequently relapse make it urgent to identify therapeutic agents with potent antitumor effect. Increasing evidence indicated that dysregulation of Wnt/β‑catenin pathway and abnormal methylation appeared to promote tumorigenesis. Arsenic trioxide (As2O3, ATO) has been reported effective in many hematologic malignancies in recent studies, however, the mechanism and effects of ATO in MCL still need further research...
September 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28900200/differential-landscape-of-non-cpg-methylation-in-embryonic-stem-cells-and-neurons-caused-by-dnmt3s
#14
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
#15
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/28893564/5-aza-2-deoxycytidine-induces-human-tenon-s-capsule-fibroblasts-differentiation-and-fibrosis-by-up-regulating-tgf-%C3%AE-type-i-receptor
#16
Shuhao Fu, Li Sun, Xiaoyan Zhang, Huimin Shi, Kang Xu, Yiqin Xiao, Wen Ye
The principle reason of high failure rate of glaucoma filtration surgery is the loss of filtration function caused by postoperative scar formation. We investigated the effects of 5-aza-2'-deoxycytidine (5-Aza-dc), a DNA methyltransferases inhibitor, on human Tenon's capsule fibroblasts (HTFs) differentiation and fibrosis and its mechanism of action, especially in relation to transforming growth factor (TGF)-β1 signaling. TGF-β1 was used to induce differentiation of cultured HTFs. 5-Aza-dc suppressed DNA methyltransferases (DNMTs) activity 6 h after treatment with a course corresponding to that of TGF-β1-induced reduction of DNMT activity without affecting cell viability as measured by Cell Counting Kit-8 assay...
September 9, 2017: Experimental Eye Research
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
#17
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
https://www.readbyqxmd.com/read/28886273/parpi-potentiates-with-current-conventional-therapy-in-mll-leukemia
#18
Lu Zhao, Chi Wai Eric So
Acute myeloid leukemias driven by MLL fusion proteins are commonly associated with poor prognosis and refractory treatment. Here, we provide evidence that olaparib can potentiate sensitivity of MLL leukemia cells to conventional chemotherapy and DNMT inhibitors offering new potential therapeutic strategies for MLL rearranged leukemias Using the primary mouse leukemia cells and human MLL-AF9 leukemic cell line, we demonstrate that treatment of MLL-AF9 leukemic cells with DNMT inhibitors or chemotherapies in combination with olaparib results in significant reduction in colony formation or cell growth while the single agent treatments had little impacts...
October 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28880816/5-aza-2-deoxycytidine-a-dna-methylation-inhibitor-induces-cytotoxicity-cell-cycle-dynamics-and-alters-expression-of-dna-methyltransferase-1-and-3a-in-mouse-hippocampus-derived-neuronal-ht22-cells
#19
Jing Yang, Xiaoli Tian, Jie Yang, Junhe Cui, Shuyuan Jiang, Rui Shi, You Liu, Xiaolei Liu, Wenqiang Xu, Wei Xie, Xiaoe Jia, Rengui Bade, Tao Zhang, Ming Zhang, Kerui Gong, Shaochun Yan, Zhanjun Yang, Guo Shao
Epigenetic processes such as DNA methylation are essential for processes of gene expression in normal mammalian development. DNA methyltransferases (DNMT) are responsible for initiating and maintaining DNA methylation. It is known that 5-Aza-CdR, an inhibitor of DNMT induces cytotoxicity by reducing DNMT activity in various tumor cell lines. However, disturbances in neuronal DNA methylation may also play a role in altered brain functions. Thus, it was of interest to determine whether alterations in DNA methylation might be associated with neuronal functions by using 5-Aza-CdR, on mouse hippocampus-derived neuronal HT22 cell line...
September 7, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28870510/repeated-transcranial-direct-current-stimulation-improves-cognitive-dysfunction-and-synaptic-plasticity-deficit-in-the-prefrontal-cortex-of-streptozotocin-induced-diabetic-rats
#20
Yi-Jen Wu, Chou-Ching Lin, Che-Ming Yeh, Miao-Er Chien, Ming-Chung Tsao, Philip Tseng, Chin-Wei Huang, Kuei-Sen Hsu
BACKGROUND: Cognitive dysfunction is commonly observed in diabetic patients. We have previously reported that anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex can facilitate visuospatial working memory in diabetic patients with concomitant diabetic peripheral neuropathy and mild cognitive impairment, but the underlying mechanisms remain unclear. OBJECTIVE: We investigated the cellular mechanisms underlying the effect of tDCS on cognitive decline in streptozotocin (STZ)-induced diabetic rats...
August 24, 2017: Brain Stimulation
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