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https://www.readbyqxmd.com/read/27913949/epigenetic-cpg-methylation-of-the-promoter-and-reactivation-of-the-expression-of-gstp1-by-astaxanthin-in-human-prostate-lncap-cells
#1
Yuqing Yang, Francisco Fuentes, Limin Shu, Chao Wang, Doug Pung, Wenji Li, Chengyue Zhang, Yue Guo, Ah-Ng Kong
Astaxanthin (AST), a red dietary carotenoid, has synergistic antioxidant effects with polyunsaturated fatty acids at low concentrations via Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or Nrf2)/antioxidant response element (ARE) signaling. In addition, chromatin remodeling and DNA methylation-based gene silencing represent a common mechanism in prostate carcinogenesis and tumor progression from normal cells to pre-initiated cells and ultimately to invasive carcinoma. Therefore, the control of epigenetic modification and the transcriptional/translational control of the activation of Nrf2 and Nrf2-target genes, including glutathione S-transferases (GSTs), appear to be an important mechanism that protects cells against injuries from oxidative stress and cancer development...
December 2, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27913254/quetiapine-treatment-reverses-depressive-like-behavior-and-reduces-dna-methyltransferase-activity-induced-by-maternal-deprivation
#2
Zuleide M Ignácio, Gislaine Z Réus, Helena M Abelaira, Amanda L Maciel, Airam B de Moura, Danyela Matos, Júlia P Demo, Júlia B I da Silva, Fernanda F Gava, Samira S Valvassori, André F Carvalho, João Quevedo
Stress in early life has been appointed as an important phenomenon in the onset of depression and poor response to treatment with classical antidepressants. Furthermore, childhood trauma triggers epigenetic changes, which are associated with the pathophysiology of major depressive disorder (MDD). Treatment with atypical antipsychotics such as quetiapine, exerts therapeutic effect for MDD patients and induces epigenetic changes. This study aimed to analyze the effect of chronic treatment with quetiapine (20mg/kg) on depressive-like behavior of rats submitted to maternal deprivation (MD), as well as the activity of histone acetylation by the enzymes histone acetyl transferases (HAT) and deacetylases (HDAC) and DNA methylation, through DNA methyltransferase enzyme (DNMT) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and hippocampus...
November 29, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27904655/increased-set1-binding-at-the-promoter-induces-aberrant-epigenetic-alterations-and-up-regulates-cyclic-adenosine-5-monophosphate-response-element-modulator-alpha-in-systemic-lupus-erythematosus
#3
Qing Zhang, Shu Ding, Huilin Zhang, Hai Long, Haijing Wu, Ming Zhao, Vera Chan, Chak-Sing Lau, Qianjin Lu
BACKGROUND: Up-regulated cyclic adenosine 5'-monophosphate response element modulator α (CREMα) which can inhibit IL-2 and induce IL-17A in T cells plays a critical role in the pathogenesis of systemic lupus erythematosus (SLE). This research aimed to investigate the mechanisms regulating CREMα expression in SLE. RESULTS: From the chromatin immunoprecipitation (ChIP) microarray data, we found a sharply increased H3 lysine 4 trimethylation (H3K4me3) amount at the CREMα promoter in SLE CD4+ T cells compared to controls...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27865785/dnmt1-dnmt3a-and-dnmt3b-cooperate-in-photoreceptor-and-outer-plexiform-layer-development-in-the-mammalian-retina
#4
Ratnesh K Singh, Ramya K Mallela, Abigail Hayes, Nicholas R Dunham, Morgan E Hedden, Raymond A Enke, Robert N Fariss, Hal Sternberg, Michael D West, Igor O Nasonkin
Characterizing the role of epigenetic regulation in the mammalian retina is critical for understanding fundamental mechanisms of retinal development and disease. DNA methylation, an epigenetic modifier of genomic DNA, plays an important role in modulating networks of tissue and cell-specific gene expression. However, the impact of DNA methylation during retinal development and homeostasis of retinal neurons remains unclear. Here, we have created a tissue-specific DNA methyltransferase (Dnmt) triple mutant mouse in an effort to characterize the impact of DNA methylation in retinal development and homeostasis...
November 16, 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/27857218/tet1-dependent-epigenetic-modification-of-bdnf-expression-in-dorsal-horn-neurons-mediates-neuropathic-pain-in-rats
#5
Ming-Chun Hsieh, Cheng-Yuan Lai, Yu-Cheng Ho, Hsueh-Hsiao Wang, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
Ten-eleven translocation methylcytosine dioxygenase 1 (Tet1) mediates the conversion of 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC), hence promoting DNA demethylation. Although recent studies have linked the DNA demethylation of specific genes to pain hypersensitivity, the role of spinal Tet1-dependent DNA demethylation in nociception hypersensitivity development remains elusive. Here, we report correlated with behavioral allodynia, spinal nerve ligation (SNL) upregulated Tet1 expression in dorsal horn neurons that hydroxylate 5 mC to 5 hmC at CpG dinucleotides in the bdnf promoter to promote spinal BDNF expression at day 7 after operation...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27852009/treatment-of-cardiovascular-pathology-with-epigenetically-active-agents-focus-on-natural-and-synthetic-inhibitors-of-dna-methylation-and-histone-deacetylation
#6
REVIEW
Dimitry A Chistiakov, Alexander N Orekhov, Yuri V Bobryshev
Cardiovascular disease (CVD) retains a leadership as a major cause of human death worldwide. Although a substantial progress was attained in the development of cardioprotective and vasculoprotective drugs, a search for new efficient therapeutic strategies and promising targets is under way. Modulation of epigenetic CVD mechanisms through administration epigenetically active agents is one of such new approaches. Epigenetic mechanisms involve heritable changes in gene expression that are not linked to the alteration of DNA sequence...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27826836/enzymology-of-mammalian-dna-methyltransferases
#7
Renata Z Jurkowska, Albert Jeltsch
DNA methylation is currently one of the hottest topics in basic and biomedical research. Despite tremendous progress in understanding the structures and biochemical properties of the mammalian DNA nucleotide methyltransferases (DNMTs), principles of their regulation in cells have only begun to be uncovered. In mammals, DNA methylation is introduced by the DNMT1, DNMT3A, and DNMT3B enzymes, which are all large multi-domain proteins. These enzymes contain a catalytic C-terminal domain with a characteristic cytosine-C5 methyltransferase fold and an N-terminal part with different domains that interacts with other proteins and chromatin and is involved in targeting and regulation of the DNMTs...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27818231/epigenetic-reactivation-of-rassf1a-by-phenethyl-isothiocyanate-peitc-and-promotion-of-apoptosis-in-lncap-cells
#8
Sarandeep S S Boyanapalli, Wenji Li, Francisco Fuentes, Yue Guo, Christina N Ramirez, Ximena-Parades Gonzalez, Douglas Pung, Ah-Ng Tony Kong
Epigenetic silencing of tumor suppressor genes is a phenomenon frequently observed in multiple cancers. Ras-association domain family 1 isoform A (RASSF1A) is a well-characterized tumor suppressor that belongs to the Ras-association domain family. Several studies have demonstrated that hypermethylation of the RASSF1A promoter is frequently observed in lung, prostate, and breast cancers. Phenethyl isothiocyanate (PEITC), a phytochemical abundant in cruciferous vegetables, possesses chemopreventive activities; however, its potential involvement in epigenetic mechanisms remains elusive...
November 3, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27817038/dna-methyltransferase-3a-promoter-polymorphism-is-associated-with-the-risk-of-human-spontaneous-abortion-after-assisted-reproduction-techniques-and-natural-conception
#9
Yudong Liu, Haiyan Zheng, Pingping Guo, Shuxian Feng, Xingyu Zhou, Desheng Ye, Xin Chen, Shiling Chen
PURPOSE: The aim of this study was to explore the association of the DNA-methyltransferase (DNMT)-3A and DNMT3B promoter polymorphisms with the risk of human spontaneous abortion after assisted reproduction techniques (ARTs) and natural conception. METHODS: We collected tissues from women who underwent abortion procedures: (a) chorionic villus samples (CVS) and muscle samples (MS) from spontaneous abortions conceived by ART and natural cycle (study group), n = 152; and (b) CVS and MS from normal early pregnancy and second trimester (control group), n = 155...
November 5, 2016: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/27787562/the-role-of-dna-methylation-in-the-metabolic-memory-phenomenon-associated-with-the-continued-progression-of-diabetic-retinopathy
#10
Manish Mishra, Renu A Kowluru
Purpose: Clinical and experimental studies have shown that diabetic retinopathy progression does not halt after termination of hyperglycemia, suggesting a "metabolic memory" phenomenon. DNA is highly dynamic, and cytosine methylation changes can last for several years. In diabetes, DNA methylation regulates expression of many genes associated with retinal mitochondrial homeostasis. Our aim was to investigate the role of DNA methylation in the metabolic memory. Methods: Reversal of 4 days of 20 mM glucose by 4 to 8 days of 5 mM glucose, in the presence/absence of Dnmt inhibitor (5-aza-2'-deoxycytidine), was investigated on DNA methylation and its machinery in human retinal endothelial cells...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27785591/the-dna-methyltransferase-inhibitor-zebularine-exerts-antitumor-effects-and-reveals-batf2-as-a-poor-prognostic-marker-for-childhood-medulloblastoma
#11
Augusto Faria Andrade, Kleiton Silva Borges, Veridiana Kiill Suazo, Lenisa Geron, Carolina Alves Pereira Corrêa, Angel Mauricio Castro-Gamero, Elton José Rosas de Vasconcelos, Ricardo Santos de Oliveira, Luciano Neder, José Andres Yunes, Simone Dos Santos Aguiar, Carlos Alberto Scrideli, Luiz Gonzaga Tone
Medulloblastoma (MB) is the most common solid tumor among pediatric patients and corresponds to 20 % of all pediatric intracranial tumors in this age group. Its treatment currently involves significant side effects. Epigenetic changes such as DNA methylation may contribute to its development and progression. DNA methyltransferase (DNMT) inhibitors have shown promising anticancer effects. The agent Zebularine acts as an inhibitor of DNA methylation and shows low toxicity and high efficacy, being a promising adjuvant agent for anti-cancer chemotherapy...
October 26, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27780634/an-oligodeoxyribonucleotide-containing-5-formyl-2-deoxycytidine-fc-at-the-cpg-site-forms-a-covalent-complex-with-dna-cytosine-5-methyltransferases-dnmts
#12
Kousuke Sato, Kyoji Kawamoto, Shintaro Shimamura, Satoshi Ichikawa, Akira Matsuda
5-Methylcytosine (mC) is known to induce epigenetic changes. Ten-eleven translocation (TET) enzymes produce the further oxidized 5-substituted cytosine derivatives, 5-formylcytosine (fC) and 5-carboxylcytosine (caC). However, their roles are unclear thus far. Here, we synthesized oligodeoxyribonucleotides (ODNs) containing 5-formyl-2'-deoxycytidine and examined their interactions with DNA cytosine-5 methyltransferase (DNMT). We found that the ODN sequence containing fCpG formed a covalent complex with both bacterial and mouse recombinant DNMTs in the absence of any cofactors...
October 14, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27779916/developmental-and-thyroid-hormone-regulation-of-the-dna-methyltransferase-3a-gene-in-xenopus-tadpoles
#13
Yasuhiro Kyono, Laurent M Sachs, Patrice Bilesimo, Luan Wen, Robert J Denver
Thyroid hormone is essential for normal development in vertebrates. In amphibians, T3 controls metamorphosis by inducing tissue-specific gene regulation programs. A hallmark of T3 action is the modification of chromatin structure, which underlies changes in gene transcription. We found that mRNA for the de novo DNA methyltransferase (DNMT) dnmt3a, but not dnmt1, increased in the brain of Xenopus tadpoles during metamorphosis in parallel with plasma [T3]. Addition of T3 to the rearing water caused a time-dependent increase in dnmt3a mRNA in tadpole brain, tail, and hind limb...
December 2016: Endocrinology
https://www.readbyqxmd.com/read/27777512/long-non-coding-rna-dbccr1-003-regulate-the-expression-of-dbccr1-via-dnmt1-in-bladder-cancer
#14
Defeng Qi, Jinhui Li, Biao Que, Jialin Su, Mengxi Li, Chaofeng Zhang, Mei Yang, Guoren Zhou, Weidong Ji
BACKGROUND: Many long non coding RNAs have been identified as key modulators in cancer development. A lncRNA, DBCCR1-003, derived from the locus of tumor suppressor gene DBCCR1 (deleted in bladder cancer chromosome region 1), has unknown function. In the present study, we explored function and molecular mechanism of DBCCR1-003 in bladder cancer (BC) development. METHODS: We evaluated the expression levels of DBCCR1-003 in tissues and cells with western blot and quantitative real-time polymerase chain reaction...
2016: Cancer Cell International
https://www.readbyqxmd.com/read/27774769/developmental-dna-methyltransferase-expression-in-the-fire-ant-solenopsis-invicta
#15
Sasha Kay, Daniel Skowronski, Brendan G Hunt
DNA methylation is accomplished in animals by two classes of enzymes known as DNA methyltransferases, DNMT3 and DNMT1, which perform de novo methylation and maintenance methylation, respectively. Several studies of hymenopteran eusocial insects suggest that DNA methylation is capable of influencing developmental plasticity. However, fundamental questions remain about the patterning of DNA methylation during the course of insect development. In this study, we performed quantitative real-time PCR (qPCR) on transcripts from the single-copy orthologs of DNMT1 and DNMT3 in the red imported fire ant, Solenopsis invicta...
October 24, 2016: Insect Science
https://www.readbyqxmd.com/read/27770540/a-minicircuitry-of-microrna-9-1-and-runx1-runx1t1-contributes-to-leukemogenesis-in-t-8-21-acute-myeloid-leukemia
#16
Lin Fu, Jinlong Shi, Anqi Liu, Lei Zhou, Mengmeng Jiang, Huaping Fu, Keman Xu, Dandan Li, Ailing Deng, Qingyi Zhang, Yifan Pang, Yujie Guo, Kai Hu, Jiansuo Zhou, Yapeng Wang, Wenrong Huang, Yu Jing, Liping Dou, Lili Wang, Kailin Xu, Xiaoyan Ke, Clara Nervi, Yonghui Li, Li Yu
MicroRNA-9-1(miR-9-1) plays an important role in the mechanism that regulates the lineage fate of differentiating hematopoietic cells. Recent studies have shown that miR-9-1 is downregulated in t (8; 21) AML. However, the pathogenic mechanisms underlying miR-9-1 down-regulation and the RUNX1-RUNX1T1 fusion protein, generated from the translocation of t (8; 21) in AML, remain unclear. RUNX1-RUNX1T1 can induce leukemogenesis through resides in and functions as a stable RUNX1-RUNX1T1-containing transcription factor complex...
October 22, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27766038/indoxyl-sulfate-enhance-the-hypermethylation-of-klotho-and-promote-the-process-of-vascular-calcification-in-chronic-kidney-disease
#17
Jing Chen, Xiaoyan Zhang, Han Zhang, Tongqiang Liu, Hui Zhang, Jie Teng, Jun Ji, Xiaoqiang Ding
Chronic kidney disease (CKD) is a state of Klotho deficiency. The Klotho expression may be suppressed due to DNA hypermethylation in cancer cells so we have investigated the effects and possible mechanisms by which Klotho expression is regulated in human aortic smooth muscle cells (HASMCs). The vascular Klotho hypermethylation in radial arteries of patients with end-stage renal disease was described. Cultured HASMCs and 5/6-nephrectomized Sprague Dawley (SD) rats treated with indoxyl sulfate (IS) were used as in vitro and in vivo models, respectively...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27764816/dnmt3b-in-vitro-knocking-down-is-able-to-reverse-embryonal-rhabdomyosarcoma-cell-phenotype-through-inhibition-of-proliferation-and-induction-of-myogenic-differentiation
#18
Francesca Megiorni, Simona Camero, Simona Ceccarelli, Heather P McDowell, Olga Mannarino, Francesco Marampon, Barry Pizer, Rajeev Shukla, Antonio Pizzuti, Cinzia Marchese, Anna Clerico, Carlo Dominici
Aberrant DNA methylation has been frequently observed in many human cancers, including rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. To date, the expression and function of the de novo DNA methyltransferase (DNMT) 3B in RMS have not yet been investigated. Our study show for the first time a significant up-regulation of DNMT3B levels in 14 RMS tumour samples and 4 RMS cell lines in comparison to normal skeletal muscle. Transfection of RD and TE671 cells, two in vitro models of embryonal RMS (ERMS), with a synthetic DNMT3B siRNA decreased cell proliferation by arresting cell cycle at G1 phase, as demonstrated by the reduced expression of Cyclin B1, Cyclin D1 and Cyclin E2, and by the concomitant up-regulation of the checkpoint regulators p21 and p27...
October 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27730812/sensitive-electrochemical-detection-of-human-methyltransferase-based-on-a-dual-signal-amplification-strategy-coupling-gold-nanoparticle-dna-complexes-with-ru-iii-redox-recycling
#19
Hui Zhang, Huilei Dong, Guoqing Yang, Hongfei Chen, Chenxin Cai
Effective detection of DNA methyltransferase (DNMT) activity is significant for cancer research. Herein, we developed a sensitive electroanalytical method to detect human DNA (cytosine-5)-methyltransferase1 (DNMT1) from crude lysates of cancer cells. In this assay, capture DNA having a preferred DNMT1 methylation site was immobilized on a gold electrode, then hybridized with gold nanoparticle (Au NP)-DNA complexes. The modified electrodes were equilibrated with the lysate, and then incubated with methylation-sensitive restriction enzyme...
October 12, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27728808/enhancing-the-cytotoxic-effects-of-parp-inhibitors-with-dna-demethylating-agents-a-potential-therapy-for-cancer
#20
Nidal E Muvarak, Khadiza Chowdhury, Limin Xia, Carine Robert, Eun Yong Choi, Yi Cai, Marina Bellani, Ying Zou, Zeba N Singh, Vu H Duong, Tyler Rutherford, Pratik Nagaria, Søren M Bentzen, Michael M Seidman, Maria R Baer, Rena G Lapidus, Stephen B Baylin, Feyruz V Rassool
Poly (ADP-ribose) polymerase inhibitors (PARPis) are clinically effective predominantly for BRCA-mutant tumors. We introduce a mechanism-based strategy to enhance PARPi efficacy based on DNA damage-related binding between DNA methyltransferases (DNMTs) and PARP1. In acute myeloid leukemia (AML) and breast cancer cells, DNMT inhibitors (DNMTis) alone covalently bind DNMTs into DNA and increase PARP1 tightly bound into chromatin. Low doses of DNMTis plus PARPis, versus each drug alone, increase PARPi efficacy, increasing amplitude and retention of PARP1 directly at laser-induced DNA damage sites...
October 10, 2016: Cancer Cell
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