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https://www.readbyqxmd.com/read/29159499/redistribution-of-cell-cycle-by-arsenic-trioxide-is-associated-with-demethylation-and-expression-changes-of-cell-cycle-related-genes-in-acute-promyelocytic-leukemia-cell-line-nb4
#1
Saeed Hassani, Ali Khaleghian, Shahin Ahmadian, Shaban Alizadeh, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation in acute promyelocytic leukemia (APL). Transcription induction and recruitment of DNA methyltransferases (DNMTs) by PML-RARα and subsequent hypermethylation are components of this perturbation. Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARα induces cell cycle change and apoptosis. How ATO causes cell cycle alteration has remained largely unexplained. Here, we investigated DNA methylation patterns of cell cycle regulatory genes promoters, the effects of ATO on the methylated genes and cell cycle distribution in an APL cell line, NB4...
November 20, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29157677/dna-methylation-affects-the-lifespan-of-honey-bee-apis-mellifera-l-workers-evidence-for-a-regulatory-module-that-involves-vitellogenin-expression-but-is-independent-of-juvenile-hormone-function
#2
Carlos A M Cardoso-Júnior, Karina R Guidugli-Lazzarini, Klaus Hartfelder
The canonic regulatory module for lifespan of honey bee (Apis mellifera) workers involves a mutual repressor relationship between juvenile hormone (JH) and vitellogenin (Vg). Compared to vertebrates, however, little is known about a possible role of epigenetic factors. The full genomic repertoire of DNA methyltransferases (DNMTs) makes the honey bee an attractive emergent model for studying the role of epigenetics in the aging process of invertebrates, and especially so in social insects. We first quantified the transcript levels of the four DNMTs encoding genes in the head thorax and abdomens of workers of different age, showing that dnmt1a and dnmt3 expression is up-regulated in abdomens of old workers, whereas dnmt1b and dnmt2 are down-regulated in heads of old workers...
November 17, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29156515/linc00152-promotes-tumorigenesis-by-regulating-dnmts-in-triple-negative-breast-cancer
#3
Jiali Wu, Zeyu Shuang, Jianfu Zhao, Hailin Tang, Peng Liu, Lijuan Zhang, Xiaoming Xie, Xiangsheng Xiao
Long noncoding RNA (lncRNA) is a significant factor that regulates various aspects of genome activity, including tumor development and progression. Linc00152, a member of lncRNA, is unregulated in various types of cancer. However, its role in breast cancer, especially in triple-negative breast cancer (TNBC), is unclear. In this study, we found that linc00152 was highly expressed in all basal-like cell lines and in the majority of TNBC tissues. Linc00152 suppression by shRNA significantly inhibited invasion and colony growth...
November 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29145563/neuronal-dnmt1-deficiency-attenuates-diet-induced-obesity-in-mice
#4
Emily C Bruggeman, John T Garretson, Rui Wu, Hang Shi, Bingzhong Xue
Aberrant neuronal DNA methylation patterns have been implicated in the promotion of obesity development, but the role of neuronal DNA methyltransferases (Dnmts; enzymes that catalyze DNA methylation) in energy balance remains poorly understood. We investigated whether neuronal Dnmt1 regulates normal energy homeostasis and obesity development using a novel Dnmt1 knockout mouse model, Dnmt1fl/fl Synapsin1Cre (ND1KO), which specifically deletes Dnmt1 in neurons.Neuronal Dnmt1 deficiency reduced adiposity in chow-fed mice and attenuated obesity in HFD-fed male mice...
November 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/29130642/dual-inhibition-of-dnmts-and-ezh2-can-overcome-both-intrinsic-and-acquired-resistance-of-myeloma-cells-to-imids-in-a-cereblon-independent-manner
#5
Konstantinos Dimopoulos, Alexandra Søgaard Helbo, Helga Fibiger Munch-Petersen, Lene Sjö, Jesper Christensen, Lasse Sommer Kristensen, Fazila Asmar, Emil Hermansen, Casey O'Connel, Peter Gimsing, Gangning Liang, Kirsten Grønbaek
Thalidomide and its derivatives, lenalidomide and pomalidomide (also known as IMiDs), have significantly changed the treatment landscape of multiple myeloma, and the recent discovery of cereblon (CRBN) as their direct biological target has led to a deeper understanding of their complex mechanism of action. In an effort to comprehend the precise mechanisms behind the development of IMiD resistance and examine whether it is potentially reversible, we established lenalidomide- (-LR) and pomalidomide-resistant (-PR) human myeloma cell lines from two IMiD-sensitive cell lines, OPM2 and NCI-H929, by continuous culture in the presence of lenalidomide or pomalidomide for 4-6 months, until acquirement of stable resistance...
November 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29115606/dna-methyltransferase-3a-modulates-chemosensitivity-to-gemcitabine-and-oxaliplatin-via-chk1-and-akt-in-p53%C3%A2-deficient-pancreatic-cancer-cells
#6
Wei Jing, Na Song, Yunpeng Liu, Xiujuan Qu, Kezuo Hou, Xianghong Yang, Xiaofang Che
The aberrant expression of DNA methyltransferases (DNMTs) has been considered to be associated with pancreatic carcinogenesis and progression. DNMT3a is widely involved in cell proliferation and cell cycle progression in pancreatic ductal adenocarcinoma (PDAC) cells. However, its regulation of chemosensitivity to gemcitabine (GEM) and oxaliplatin (OXA) in p53‑deficient PDAC remains unclear. In the present study, the effect and mechanisms of DNMT3a on GEM and OXA chemosensitivity in p53‑deficient PDAC cells were investigated using MTT assay, cell cycle analysis, apoptosis analysis and western blotting...
October 27, 2017: Molecular Medicine Reports
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
#7
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/29054638/the-persistent-organochlorine-pesticide-endosulfan-modulates-multiple-epigenetic-regulators-with-oncogenic-potential-in-mcf-7-cells
#8
Krishna Ghosh, Biji Chatterjee, Aparna Geetha Jayaprasad, Santosh R Kanade
Environmental cues and chemicals can potentially modulate the phenotypic expression of genome through alterations in the epigenetic mechanisms. Endosulfan is one of the extensively used organochlorine pesticides around the world which is known for its endocrine, neuro- and reproductive toxicity. This study was aimed to investigate the potential of α-endosulfan in modulation of multiple epigenetic enzymes in MCF-7 cells. The cells were treated with DMSO (control) or α-endosulfan (1 and 10μM) and the expression of various epigenetic enzymes was assayed by real-time PCR and immunoblotting, in addition to their activity assays...
October 17, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29045493/the-sequence-preference-of-dna-methylation-variation-in-mammalians
#9
Ling Zhang, Chan Gu, Lijiang Yang, Fuchou Tang, Yi Qin Gao
Methylation of cytosine at the 5 position of the pyrimidine ring is the most prevalent and significant epigenetic modifications in mammalian DNA. The CpG methylation level shows a bimodal distribution but the bimodality can be overestimated due to the heterogeneity of per-base depth. Here, we developed an algorithm to eliminate the effect of per-base depth inhomogeneity on the bimodality and obtained a random CpG methylation distribution. By quantifying the deviation of the observed methylation distribution and the random one using the information formula, we find that in tetranucleotides 5'-N5CGN3-3' (N5, N3 = A, C, G or T), GCGN3 and CCGN3 show less apparent deviation than ACGN3 and TCGN3, indicating that GCGN3 and CCGN3 are less variant in their level of methylation...
2017: PloS One
https://www.readbyqxmd.com/read/29038074/insights-from-pharmacological-similarity-of-epigenetic-targets-in-epipolypharmacology
#10
REVIEW
J Jesús Naveja, José L Medina-Franco
As the number of compounds tested against epigenetic targets grows, exploration of the possible associations in chemical space among these targets could lead to the identification of new drugs or new designs of epipolypharmacological molecules. Thus, here we review the compound-epitarget associations of the numerous public databases available. Specifically, we explore the structure-multitarget activity relationships and diversity of over 7000 compounds tested against 52 epigenetic-related targets. We found that, whereas inhibitors of histone deacetylases and other epigenetic targets clustered in the chemical space, the chemical space of inhibitors of different DNA methyltransferases (DNMTs) did not overlap, indicating DNMT selectivity...
October 14, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/29035547/pharmacokinetics-and-pharmacodynamics-of-the-triterpenoid-ursolic-acid-in-regulating-the-antioxidant-anti-inflammatory-and-epigenetic-gene-responses-in-rat-leukocytes
#11
Chengyue Zhang, Chao Wang, Wenji Li, Renyi Wu, Yue Guo, David Cheng, Yuqing Yang, Ioannis P Androulakis, Ah-Ng Kong
The triterpenoid ursolic acid (UA) has been proposed as a potential cancer chemopreventive agent in many preclinical and clinical studies. In the present work, we aimed to characterize the pharmacokinetics (PK) of UA and to quantitatively assess the antioxidative and anti-inflammatory effects of UA, which are potentially linked to its chemopreventive efficacy. UA was administered intravenously (i.v., 20 mg/kg) or by oral gavage (100 mg/kg) to male Sprague-Dawley rats, and blood samples were collected at a series of designated time points...
November 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29033456/the-dna-methyltransferase-family-a-versatile-toolkit-for-epigenetic-regulation
#12
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
#13
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...
December 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29024060/loss-of-dnmt3b-in-chondrocytes-leads-to-delayed-endochondral-ossification-and-fracture-repair
#14
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/29020412/emerging-role-of-one-carbon-metabolism-and-dna-methylation-enrichment-on-%C3%AE-containing-gabaa-receptor-expression-in-the-cerebellum-of-subjects-with-alcohol-use-disorders-aud
#15
Eleonora Gatta, James Auta, David P Gavin, Dulal K Bhaumik, Dennis R Grayson, Subhash C Pandey, Alessandro Guidotti
BACKGROUND: Cerebellum is an area of the brain particularly sensitive to the effects of acute and chronic alcohol consumption. Alcohol exposure decreases cerebellar Purkinje cell output by increasing GABA release from Golgi cells onto extrasynaptic α6/δ-containing GABAA receptors located on glutamatergic granule cells. Here, we studied whether chronic alcohol consumption induces changes in GABAA receptor subunit expression and whether these changes are associated with alterations in epigenetic mechanisms via DNA methylation...
August 19, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28993285/insulin-like-peptides-and-dna-trna-methyltransferases-are-involved-in-the-nutritional-regulation-of-female-reproduction-in-nilaparvata-lugens-st%C3%A3-l
#16
Kai Lu, Xia Chen, Wenru Li, Yue Li, Zhichao Zhang, Qiang Zhou
Insulin-like peptides (ILPs) sense and transduce nutritional information and are linked to female reproduction in many insect species. Our previous studies have shown that "Target of rapamycin" (TOR) pathway functions through juvenile hormone (JH) to regulate amino acids-mediated vitellogenesis in the brown planthopper, Nilaparvata lugens, one of the most destructive rice pests in Asia. Recent reports have demonstrated that DNA methyltransferases (Dnmts) are also involved in female reproduction of N. lugens...
October 7, 2017: Gene
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
#17
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/28989582/patterns-of-dnmt1-promoter-methylation-in-patients-with-acute-lymphoblastic-leukemia
#18
Tirdad Rahmani, Mehdi Azad, Bahram Chahardouli, Hajar Nasiri, Mousa Vatanmakanian, Saeid Kaviani
Background: Acute lymphoblastic leukemia (ALL) is a clonal malignant disorder characterized by an uncontrolled proliferation of immature T or B lymphocytes. Extensive studies have shown that the epigenetic changes, especially modified DNA methylation patterns in the regulatory regions through the DNA methyltransferase (DNMTs), play an important role in the development of genetic disorders and abnormal growth and maturation capacity of leukemic stem cells (LSCs).The aim of this study was to evaluate the changes in DNMT1 promoter methylation and its expression pattern in patients with ALL...
July 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
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
#19
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/28965139/epigenetic-changes-in-preimplantation-embryos-subjected-to-laser-manipulation
#20
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...
December 2017: Lasers in Medical Science
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