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https://www.readbyqxmd.com/read/29216900/treatment-with-a-dna-methyltransferase-inhibitor-feminizes-zebrafish-and-induces-long-term-expression-changes-in-the-gonads
#1
Laia Ribas, Konstantinos Vanezis, Marco Antonio Imués, Francesc Piferrer
BACKGROUND: The role of epigenetic modifications such as DNA methylation during vertebrate sexual development is far from being clear. Using the zebrafish model, we tested the effects of one of the most common DNA methyltransferase (dnmt) inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), which is approved for the treatment of acute myeloid leukaemia and is under active investigation for the treatment of solid tumours. Several dose-response experiments were carried out during two periods, including not only the very first days of development (0-6 days post-fertilization, dpf), as done in previous studies, but also, and as a novelty, the period of gonadal development (10-30 dpf)...
December 8, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29209431/combining-cytogenetic-and-epigenetic-approaches-in-chronic-lymphocytic-leukemia-improves-prognosis-prediction-for-patients-with-isolated-13q-deletion
#2
Cristina Bagacean, Christelle Le Dantec, Christian Berthou, Adrian Tempescul, Hussam Saad, Anne Bordron, Mihnea Zdrenghea, Victor Cristea, Nathalie Douet-Guilbert, Yves Renaudineau
Background: Both defective DNA methylation and active DNA demethylation processes are emerging as important risk factors in chronic lymphocytic leukemia (CLL). However, associations between 5-cytosine epigenetic markers and the most frequent chromosomal abnormalities detected in CLL remain to be established. Methods: CLL patients were retrospectively classified into a cytogenetic low-risk group (isolated 13q deletion), an intermediate-risk group (normal karyotype or trisomy 12), and a high-risk group (11q deletion, 17p deletion, or complex karyotype [≥ 3 breakpoints])...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29207141/downregulation-of-mir%C3%A2-29b-targets-dnmt3b-to-suppress-cellular-apoptosis-and-enhance-proliferation-in-pancreatic-cancer
#3
Li-Hua Wang, Ju Huang, Cheng-Rong Wu, Liu-Ye Huang, Jun Cui, Zhi-Zhi Xing, Chun-Yu Zhao
As one of the most aggressive types of tumor, pancreatic cancer is a principal cause of tumor‑associated mortality. Negative associations between microRNA‑29 (miR‑29) and DNA methyltransferases (DNMT) 3a and 3b have been demonstrated to be associated with the carcinogenesis of a number of types of cancer; however, this has not been completely elucidated in pancreatic cancer. In the present study, pancreatic cancer tissues (n=15) and corresponding paracancerous tissues (n=15) were obtained and the results of reverse transcription‑quantitative polymerase chain reaction analysis indicated decreased expression of miR‑29b and enhanced mRNA expression of DNMT3b in pancreatic cancer tissues, compared with the corresponding paracancerous tissues...
November 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29193198/the-dna-methyltransferase-inhibitor-5-aza-2-deoxycytidine-affects-humicola-grisea-enzyme-activities-and-the-glucose-mediated-gene-repression
#4
João Heitor C Manfrão-Netto, Thiago M Mello-de-Sousa, Astrid R Mach-Aigner, Robert L Mach, Marcio J Poças-Fonseca
Humicola grisea var. thermoidea (Hgvt) is a thermophilic ascomycete that produces lignocellulolytic enzymes and it is proposed for the conversion of agricultural residues into useful byproducts. Drugs that inhibit the DNA methyltransferases (DNMTs) activity are employed in epigenetic studies but nothing is known about a possible effect on the production of fungal enzymes. We evaluated the effect of 5-aza-2'-deoxycytidine (5-Aza; a chemical inhibitor of DNMTs activity) on the secreted enzyme activity and on the transcription of cellulase and xylanase genes from Hgvt grown in agricultural residues and in glucose...
November 28, 2017: Journal of Basic Microbiology
https://www.readbyqxmd.com/read/29189124/overview-on-anticancer-drug-design-and-development
#5
Sureyya Olgen
Many impediments of current anti-cancer therapies have urged scientists to discover new agents. As a result of growing spectrums of new targets and strategies and recent biological and biotechnological progresses, many anti-cancer agents such as monoclonal antibodies, small molecule tyrosine kinase inhibitors and epigenetic drugs have been reached to clinical trials. Addition to the traditional targets (mitosis, DNA synthesis, repairing systems, tumor growth, apoptosis, tumor vasculature and cell signaling mechanisms), other targets such as proteasome, heat shock proteins (HSPs), and epigenetics (HDACs, HATs, DNMT, PAD4, AID, and Tet1) are used to design new anti-cancer agents...
November 29, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29180273/evaluation-of-vitrification-protocol-of-mouse-ovarian-tissue-by-effect-of-dna-methyltransferase-1-and-paternal-imprinted-growth-factor-receptor-binding-protein-10-on-signaling-pathways
#6
Zhong-Yi He, Hong-Yan Wang, Xue Zhou, Xue-Yun Liang, Bei Yan, Rui Wang, Liang-Hong Ma, Yi-Li Wang
Transplantation of cryopreserved ovarian tissue has been considered as a promising way of fertility preservation for women. however, this cryopreservation method is prone to post-resuscitation follicle proliferation and oocyte development stagnation, affecting late transplant survival. To evaluate current vitrification works, we investigated the critical pathway alternations in vitrified-warmed juvenile 10-day-old mouse ovary. We showed a significant decrease of protein kinase B (Akt) and Mitogen-activated protein kinase (Mapk) phosphorylation, during which serine/threonine kinases play central roles in coordinating follicle and oocyte development and stress response...
November 24, 2017: Cryobiology
https://www.readbyqxmd.com/read/29167115/epigenetic-modulation-of-intestinal-na-h-exchanger-3-expression
#7
Anoop Kumar, Pooja Malhotra, Hayley P Coffing, Shubha Priyamvada, Arivarasu Natarajan Anbazhagan, Harish R Krishnan, Ravinder K Gill, Waddah A Alrefai, David P Gavin, Subhash C Pandey, Pradeep K Dudeja, Seema Saksena
Na(+)/H(+) exchanger-3 (NHE3) is crucial for intestinal Na+ absorption and its reduction has been implicated in infectious and Inflammatory Bowel Diseases (IBD)-associated diarrhea. Epigenetic mechanisms such as DNA methylation are involved in the pathophysiology of IBD. Whether changes in DNA methylation are involved in modulating intestinal NHE3 gene expression is not known. Caco-2 and HUTU-80 cells were used as models of human intestinal epithelial cells (IECs). Normal C57/BL6, wild type or GADD45b KO mice were used as in vivo models...
November 22, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29164502/superovulation-alters-dna-methyltransferase-protein-expression-in-mouse-oocytes-and-early-embryos
#8
Fatma Uysal, Saffet Ozturk, Gokhan Akkoyunlu
PURPOSE: DNA methylation is an epigenetic mechanism that plays critical roles during mammalian oocyte and preimplantation embryo development. It is achieved by adding a methyl group to the fifth carbon atom of cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinucleotide sites using DNA methyltransferase (DNMT) enzymes for de novo and maintenance methylation processes. DNMT1, DNMT3A, and DNMT3B play important roles in establishing methylation of developmentally related genes in oocytes and early embryos...
November 22, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/29148180/dna-methylation-in-the-central-and-efferent-limbs-of-the-chemo-reflex-requires-carotid-body-neural-activity
#9
Jayasri Nanduri, Ying-Jie Peng, Ning Wang, Shakil A Khan, Gregg L Semenza, Nanduri R Prabhakar
Long-term exposure to intermittent hypoxia (LT-IH; 30 days), simulating blood O2 profiles during sleep apnea, has been shown to repress anti-oxidant enzyme (AOE) gene expression by DNA methylation in the carotid body (CB) reflex pathway, resulting in persistent elevation of plasma catecholamine levels and blood pressure. The present study examined the mechanisms by which LT-IH induces DNA methylation. Adult rats exposed to LT-IH showed elevated reactive oxygen species (ROS) in the CB, nucleus tractus solitarius (nTS) and rostroventrolateral medulla (RVLM) and adrenal medulla (AM), which represent the central and efferent limbs of the CB reflex, respectively...
November 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29120412/bortezomib-induced-mirnas-direct-epigenetic-silencing-of-locus-genes-and-trigger-apoptosis-in-leukemia
#10
Yu-Yi Chu, Chiung-Yuan Ko, Shao-Ming Wang, Pin-I Lin, Han-Ying Wang, Wen-Chi Lin, Dong-Yu Wu, Lu-Hao Wang, Ju-Ming Wang
MicroRNAs (miRNAs) have been suggested to repress transcription via binding the 3'-untranslated regions of mRNAs. However, the involvement and details of miRNA-mediated epigenetic regulation, particularly in targeting genomic DNA and mediating epigenetic regulation, remain largely uninvestigated. In the present study, transcription factor CCAAT/enhancer binding protein delta (CEBPD) was responsive to the anticancer drug bortezomib, a clinical and highly selective drug for leukemia treatment, and contributed to bortezomib-induced cell death...
November 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29111877/dna-methylation-alterations-induced-by-transient-exposure-of-mcf-7-cells-to-maghemite-nanoparticles
#11
Raphael S Bonadio, Ana Carolina Arcanjo, Emilia Cd Lima, Alline T Vasconcelos, Renata C Silva, Frederico H Horst, Ricardo B Azevedo, Marcio José Poças-Fonseca, João Paulo F Longo
AIM: To evaluate the DNA methylation profile of MCF-7 cells during and after the treatment with maghemite nanoparticles (MNP-CIT). MATERIALS & METHODS: Noncytotoxic MNP-CIT concentrations and cell morphology were evaluated by standard methods. DNA methylation was assessed by whole genome bisulfite sequencing. DNA methyltransferase (DNMT) genes expression was analyzed by qRT-PCR. RESULTS: A total of 30 and 60 µgFeml(-1) MNP-CIT accumulated in cytoplasm but did not present cytotoxic effects...
November 7, 2017: Nanomedicine
https://www.readbyqxmd.com/read/29106518/prenatal-ethanol-exposure-and-neocortical-development-a-transgenerational-model-of-fasd
#12
Charles W Abbott, David J Rohac, Riley T Bottom, Sahil Patadia, Kelly J Huffman
Fetal Alcohol Spectrum Disorders, or FASD, represent a range of adverse developmental conditions caused by prenatal ethanol exposure (PrEE) from maternal consumption of alcohol. PrEE induces neurobiological damage in the developing brain leading to cognitive-perceptual and behavioral deficits in the offspring. Alcohol-mediated alterations to epigenetic function may underlie PrEE-related brain dysfunction, with these changes potentially carried across generations to unexposed offspring. To determine the transgenerational impact of PrEE on neocortical development, we generated a mouse model of FASD and identified numerous stable phenotypes transmitted via the male germline to the unexposed third generation...
July 6, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29104258/epigenetic-regulatory-mechanisms-induced-by-resveratrol
#13
REVIEW
Guilherme Felipe Santos Fernandes, Gabriel Dalio Bernardes Silva, Aline Renata Pavan, Diego Eidy Chiba, Chung Man Chin, Jean Leandro Dos Santos
Resveratrol (RVT) is one of the main natural compounds studied worldwide due to its potential therapeutic use in the treatment of many diseases, including cancer, diabetes, cardiovascular diseases, neurodegenerative diseases and metabolic disorders. Nevertheless, the mechanism of action of RVT in all of these conditions is not completely understood, as it can modify not only biochemical pathways but also epigenetic mechanisms. In this paper, we analyze the biological activities exhibited by RVT with a focus on the epigenetic mechanisms, especially those related to DNA methyltransferase (DNMT), histone deacetylase (HDAC) and lysine-specific demethylase-1 (LSD1)...
November 1, 2017: Nutrients
https://www.readbyqxmd.com/read/29100357/dnmt3b-overexpression-contributes-to-aberrant-dna-methylation-and-myc-driven-tumor-maintenance-in-t-all-and-burkitt-s-lymphoma
#14
Candace J Poole, Wenli Zheng, Atul Lodh, Aleksey Yevtodiyenko, Daniel Liefwalker, Honglin Li, Dean W Felsher, Jan van Riggelen
Aberrant DNA methylation is a hallmark of cancer. However, our understanding of how tumor cell-specific DNA methylation patterns are established and maintained is limited. Here, we report that in T-cell acute lymphoblastic leukemia (T-ALL) and Burkitt's lymphoma the MYC oncogene causes overexpression of DNA methyltransferase (DNMT) 1 and 3B, which contributes to tumor maintenance. By utilizing a tetracycline-regulated MYC transgene in a mouse T-ALL (EμSRα-tTA;tet-o-MYC) and human Burkitt's lymphoma (P493-6) model, we demonstrated that DNMT1 and DNMT3B expression depend on high MYC levels, and that their transcription decreased upon MYC-inactivation...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29095264/effects-of-age-and-sex-on-epigenetic-modification-induced-by-an-acute-physical-exercise
#15
Marinella Coco, Vincenzo Perciavalle, Paolo Cavallari, Francesco Bolzoni, Adriana Carol Eleonora Graziano, Valentina Perciavalle
It has been observed that, after 2 hours of aerobic exercise, plasma interleukin-6 (IL-6) increases whereas nuclear concentrations of enzyme DNA methyltransferase (DNMT) 3B significantly decreased in peripheral blood mononuclear cells (PBMCs), with no change observed in DNMT3A. The aim of the present study was to detect differences in these changes induced by exercise in plasma IL-6 levels as well as in PBMC nuclear concentrations of DNMT3A and DNMT3B, in relation to age and sex. Four groups were studied: 12 young men (24...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29075135/dnmt3a-methylation-in-neuropathic-pain
#16
Cuijie Shao, Yong Gao, Dan Jin, Xin Xu, Shuying Tan, Hui Yu, Qingxiang Zhao, Li Zhao, Wansheng Wang, Deqiang Wang
BACKGROUND: Mu opioid receptor (MOR) plays a crucial role in mediating analgesic effects of opioids and is closely associated with the pathologies of neuropathic pain. Previous studies have reported that peripheral nerve injury downregulates MOR expression, but the epigenetic mechanisms remain unknown. OBJECTIVE: Therefore, we investigated DNA methyltransferase3a (DNMT3a) expression or methylation changes within MOR promoter in the spinal cord in a neuropathic pain induced by a chronic constriction injury (CCI) mouse model and further determined whether these injury-associated changes are reversible by pharmacological interventions...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/29074949/erratum-dnmt-and-hdac-inhibitors-induce-cryptic-transcription-start-sites-encoded-in-long-terminal-repeats
#17
David Brocks, Christopher R Schmidt, Michael Daskalakis, Hyo Sik Jang, Nakul M Shah, Daofeng Li, Jing Li, Bo Zhang, Yiran Hou, Sara Laudato, Daniel B Lipka, Johanna Schott, Holger Bierhoff, Yassen Assenov, Monika Helf, Alzbeta Ressnerova, Md Saiful Islam, Anders M Lindroth, Simon Haas, Marieke Essers, Charles D Imbusch, Benedikt Brors, Ina Oehme, Olaf Witt, Michael Lübbert, Jan-Philipp Mallm, Karsten Rippe, Rainer Will, Dieter Weichenhan, Georg Stoecklin, Clarissa Gerhäuser, Christopher C Oakes, Ting Wang, Christoph Plass
This corrects the article DOI: 10.1038/ng.3889.
October 27, 2017: Nature Genetics
https://www.readbyqxmd.com/read/29074164/defective-regulation-of-l1-endogenous-retroelements-in-primary-sjogren-s-syndrome-and-systemic-lupus-erythematosus-role-of-methylating-enzymes
#18
Clio P Mavragani, Adrianos Nezos, Irina Sagalovskiy, Surya Seshan, Kyriakos A Kirou, Mary K Crow
OBJECTIVE: To investigate whether altered DNA methylation contributes to the inappropriate expression of LINE-1 (L1) retroelements in primary Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE). METHODS: Minor salivary glands (MSG) were obtained from 42 patients with primary SS [23 without adverse predictors for lymphoma development (SS-low risk), 7 SS-high risk and 12 complicated by B-cell lymphoma (SS-lymphoma)] and 17 sicca controls (SC). Additionally, kidney biopsy specimens and PBMCs were obtained from 23 and 73 lupus patients, respectively...
October 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29070120/-expression-of-dnmt3b-gene-in-myeloma-rpmi-8226-cells-and-its-biological-significance
#19
Xiao-Ning Wang, Jian-Na Yao, Xiao-Juan Wang, Chun-Hong Sun, Cai-Li Guo, Ying Chen, Peng-Cheng He, Mei Zhang
OBJECTIVE: To study the expression of DNMT3b gene in myeloma RPMI8226 cells and its biological significance. METHODS: The activity of DNA methyltransferase was detected by ELISA, and the expression of DNMT3b in RPMI8226 cells was analyzed by semi-quantitative RT-PCR and real-time fluorescent quantitative PCR. The proliferation and expression of DNMT3b gene in RPMI8226 cells intervened with capecitabine for 24 hours were detected. RESULTS: The activity of DNMT and expression of DNMT3b in RPMI 8226 cells increased...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29069387/functional-role-of-dna-methylation-at-the-flo1-promoter-in-budding-yeast
#20
Kei-Ichi Sugiyama, Hiroko Furusawa, Petr Grúz, Masamitsu Honma
We have previously reported that the transformation of the budding yeast with plasmids encoding the human DNA methyltransferases DNMT1 and DNMT3B cDNAs induce the mRNA of flocculin gene FLO1 and the flocculation phenotype. In the present study, we evaluated the effect of DNMT inhibitor in the transformed yeasts using a FLO1 promoter-based green fluorescent protein (GFP) reporter gene assay. The DNMT inhibitor, 5-aza-2'-deoxycytidine (5AZ), decreased GFP fluorescence driven by FLO1 promoter in DNMT -genes transformed yeast ( DNMT yeast)...
October 24, 2017: FEMS Microbiology Letters
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