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DNA demethylation

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https://www.readbyqxmd.com/read/28205560/alkb-homolog-3-mediated-trna-demethylation-promotes-protein-synthesis-in-cancer-cells
#1
Yuko Ueda, Ikumi Ooshio, Yasuyuki Fusamae, Kaori Kitae, Megumi Kawaguchi, Kentaro Jingushi, Hiroaki Hase, Kazuo Harada, Kazumasa Hirata, Kazutake Tsujikawa
The mammalian AlkB homolog (ALKBH) family of proteins possess a 2-oxoglutarate- and Fe(II)-dependent oxygenase domain. A similar domain in the Escherichia coli AlkB protein catalyzes the oxidative demethylation of 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) in both DNA and RNA. AlkB homolog 3 (ALKBH3) was also shown to demethylate 1-meA and 3-meC (induced in single-stranded DNA and RNA by a methylating agent) to reverse the methylation damage and retain the integrity of the DNA/RNA. We previously reported the high expression of ALKBH3 in clinical tumor specimens and its involvement in tumor progression...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28204824/dna-methylation-mediated-caspase-8-downregulation-is-associated-with-anti-apoptotic-activity-and-human-malignant-glioma-grade
#2
Yueqiu Teng, Yu-Cui Dong, Zhaoyu Liu, Yan Zou, Hui Xie, Yu Zhao, Jun Su, Fenglin Cao, Hua Jin, Huan Ren
The methylation-mediated silencing of tumor suppressors, including key apoptosis-related genes plays an important role in the pathogenesis and therapeutic resistance in human cancer. In this study, we aimed to elucidate the role and mechanisms of resistance to apoptosis with caspase-8 gene downregulation in human malignant glioma. Reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP) were used to examine caspase-8 expressoin at the mRNA level and gene methylation status in normal brain tissue, glioma tissue and cancer cell lines...
February 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28198363/gut-memories-do-not-fade-epigenetic-regulation-of-lasting-gut-homing-receptor-expression-in-cd4-memory-t-cells
#3
B A Szilagyi, J Triebus, C Kressler, M de Almeida, S Tierling, P Durek, M Mardahl, A Szilagyi, S Floess, J Huehn, U Syrbe, J Walter, J K Polansky, A Hamann
The concept of a "topographical memory" in lymphocytes implies a stable expression of homing receptors mediating trafficking of lymphocytes back to the tissue of initial activation. However, a significant plasticity of the gut-homing receptor α4β7 was found in CD8(+) T cells, questioning the concept. We now demonstrate that α4β7 expression in murine CD4(+) memory T cells is, in contrast, imprinted and remains stable in the absence of the inducing factor retinoic acid (RA) or other stimuli from mucosal environments...
February 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28192139/vitamin-c-down-regulate-apo-a-expression-via-tet2-dependent-dna-demethylation-in-hepg2-cells
#4
Kai Qu, Xiao-Feng Ma, Guo-Hua Li, Hai Zhang, Ya-Mi Liu, Kai Zhang, Jun-Fa Zeng, Jian-Jun Lei, Dang-Heng Wei, Zuo Wang
Lipoprotein(a)[Lp(a)] is a risk factor for coronary heart diseases. However, the metabolism of this protein remains poorly understood. Efficient and specific drugs that can decrease high plasma levels of Lp(a) have not been developed yet. Vitamin C is responsible for maintaining the catalytic activity of a group of iron and 2-oxoglutarate (2OG)-dependent dioxygenases and induces the generation of 5-hydroxymethylcytosine (5hmC) via Ten-eleven translocation (Tet) dioxygenases. In addition, It has been reported vitamin C deficiency induces atherosclerosis and increases Lp(a) and apo(a) plasma levels in Lp(a)+ mice...
February 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28188826/convenient-expression-purification-and-quantitative-liquid-chromatography-tandem-mass-spectrometry-based-analysis-of-tet2-5-methylcytosine-demethylase
#5
Mohit Jaiswal, Subhradeep Bhar, Harika Vemula, Swami Prakash, V K Chaithanya Ponnaluri, William G Gutheil, Mridul Mukherji
5-Methylcytosine within CpG islands in DNA plays a crucial role in epigenetic transcriptional regulation during metazoan development. Recently, it has been established that the Ten-Eleven Translocation (TET) family, Fe(II)- and 2-oxoglutarate (2OG/αKG)-dependent oxygenases initiate 5-methylcytosine demethylation by iterative oxidation reactions. Mutations in the TET2 gene are frequently detected in patients with myeloid malignancies. Here, we describe the cloning of untagged human TET2 demethylase using Gateway technology and its efficient expression in E...
February 8, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28186961/combination-epigenetic-therapy-in-metastatic-colorectal-cancer-mcrc-with-subcutaneous-5-azacitidine-and-entinostat-a-phase-2-consortium-stand-up-2-cancer-study
#6
Nilofer S Azad, Anthony El-Khoueiry, Jun Yin, Ann L Oberg, Patrick Flynn, Douglas Adkins, Anup Sharma, Daniel J Weisenberger, Thomas Brown, Prakriti Medvari, Peter A Jones, Hariharan Easwaran, Ihab Kamel, Nathan Bahary, George Kim, Joel Picus, Henry C Pitot, Charles Erlichman, Ross Donehower, Hui Shen, Peter W Laird, Richard Piekarz, Stephen Baylin, Nita Ahuja
PURPOSE: Therapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies. EXPERIMENTAL DESIGN: We conducted a phase II, multi-institutional study of the combination in metastatic CRC patients. Subcutaneous azacitidine was administered at 75 mg/m2 days 1-5 and 8-10 and entinostat was given 7 mg orally on days 3 and 10...
February 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178884/improved-post-thaw-function-and-epigenetic-changes-in-mesenchymal-stromal-cells-cryopreserved-using-multicomponent-osmolyte-solutions
#7
Kathryn Pollock, Rebekah Samsonraj, Amel Dudakovic, Roman Thaler, Aron Stumbras, David McKenna, Peter Dosa, Andre van Wijnen, Allison Hubel
Current methods for freezing mesenchymal stromal cells (MSCs) result in poor post-thaw function, which limits the clinical utility of these cells. This investigation develops a novel approach to preserve MSCs using combinations of sugars, sugar alcohols and small molecule additives. MSCs frozen using these solutions exhibit improved post-thaw attachment and a more normal alignment of the actin cytoskeleton compared to cells exposed to dimethylsulfoxide (DMSO). Osteogenic and chondrogenic differentiation assays show that cells retain their mesenchymal lineage properties...
February 8, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28169463/relationship-between-epigenetic-regulation-dietary-habits-and-the-developmental-origins-of-health-and-disease-theory
#8
REVIEW
Kazuki Mochizuki, Natsuyo Hariya, Kazue Honma, Toshinao Goda
Environmental stressors during developmental stages are hypothesized to increase the risk of developing metabolic diseases such as obesity, type 2 diabetes, hypertension, and psychiatric diseases during later life. This theory is known as the Developmental Origins of Health and Disease (DOHaD). Recent studies suggest that accumulation of environmental stress, including during developmental stages, is internalized as acquired information designated as "epigenetic memory." This epigenetic memory is generally indicated as DNA methylation and histone modifications in the chromatin...
February 7, 2017: Congenital Anomalies
https://www.readbyqxmd.com/read/28169339/dna-methylation-governs-the-dynamic-regulation-of-inflammation-by-apoptotic-cells-during-efferocytosis
#9
Clare A Notley, Christine K Jordan, Jenny L McGovern, Mark A Brown, Michael R Ehrenstein
Efficient clearance of apoptotic cells (AC) is pivotal in preventing autoimmunity and is a potent immunosuppressive stimulus. However, activation of cells prior to apoptosis abolishes their immunoregulatory properties. Here we show using the antigen-induced model of arthritis that the degree of DNA methylation within AC confers their immunomodulatory plasticity. DNA isolated from resting and activated AC mimicked their respective immune effects. Demethylation of DNA abrogated the protective effect of AC whereas remethylation of AC DNA reversed the effects of activation and restored the ability to inhibit inflammation...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167789/dnmt3a-restrains-mast-cell-inflammatory-responses
#10
Cristina Leoni, Sara Montagner, Andrea Rinaldi, Francesco Bertoni, Sara Polletti, Chiara Balestrieri, Silvia Monticelli
DNA methylation and specifically the DNA methyltransferase enzyme DNMT3A are involved in the pathogenesis of a variety of hematological diseases and in regulating the function of immune cells. Although altered DNA methylation patterns and mutations in DNMT3A correlate with mast cell proliferative disorders in humans, the role of DNA methylation in mast cell biology is not understood. By using mast cells lacking Dnmt3a, we found that this enzyme is involved in restraining mast cell responses to acute and chronic stimuli, both in vitro and in vivo...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28155862/synergetic-effects-of-dna-methylation-and-histone-modification-during-mouse-induced-pluripotent-stem-cell-generation
#11
Guiying Wang, Rong Weng, Yuanyuan Lan, Xudong Guo, Qidong Liu, Xiaoqin Liu, Chenqi Lu, Jiuhong Kang
DNA methylation and histone methylation (H3K27me3) have been reported as major barriers to induced pluripotent stem cell (iPSC) generation using four core transcription factors (Oct4, Sox2, Klf4, and c-Myc, termed OSKM). Here, to illustrate the possibility of deriving iPSCs via demethylation, as well as the exact effects of DNA methylation and histone modification on gene expression regulation, we performed RNA sequencing to characterize the transcriptomes of ES cells and iPSCs derived by demethylation with miR-29b or shDnmt3a, and carried out integrated analyses...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28150354/tet1-promotes-cisplatin-resistance-via-demethylating-the-vimentin-promoter-in-ovarian-cancer
#12
Xi Han, Yuanyuan Zhou, Yuanyi You, Jiaojiao Lu, Lijie Wang, Huilian Hou, Jing Li, Wei Chen, Le Zhao, Xu Li
The development of chemo-resistance impairs the outcome of the first line platinum-based chemotherapies for ovarian cancer. Deregulation of DNA methylation/demethylation provides a critical mechanism for the occurrence of chemo-resistance. The ten-eleven translocation (TET) family of dioxygenases including TET1/2/3 plays an important part in DNA demethylation, but their roles in cisplatin resistance have not been elucidated. Using cisplatin-sensitive and cisplatin-resistant ovarian cancer cell models, we found that TET1 was significantly upregulated in cisplatin-resistant CP70 cells compared with that in cisplatin-sensitive A2780 cells...
February 2, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28150227/apobec1-promotes-neurotoxicity-induced-dedifferentiation-of-m%C3%A3-ller-glial-cells
#13
Jian Xiao, Xue Li, Lan Chen, Xin Han, Wei Zhao, Lianlian Li, Jie-Guang Chen
Retinal Müller glial cells in mammals acquire stem and progenitor cell properties after neurotoxic treatment. However, the molecular mechanisms underlying proliferation and dedifferentiation of adult Müller cells in the mammalian retina were unclear. In this study, treatments with N-methyl-D-aspartate (NMDA) plus epidermal growth factor (EGF) led to the proliferation of Müller cells and expression of stem cell markers including Nanog and Nestin in the retina. The increased mRNA for Nanog and Nestin were coincident with reduced methylation of a Nanog promoter and a Nestin enhancer specific in the neural stem cells, respectively...
February 2, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28149332/the-immunomodulatory-anticancer-agent-rrx-001-induces-an-interferon-response-through-epigenetic-induction-of-viral-mimicry
#14
Hongjuan Zhao, Shoucheng Ning, Rosalie Nolley, Jan Scicinski, Bryan Oronsky, Susan J Knox, Donna M Peehl
BACKGROUND: RRx-001, a dinitroazetidine derivative, is a novel anticancer agent currently in phase II clinical trials. It mediates immunomodulatory effects either directly through polarization of tumor associated macrophages or indirectly through vascular normalization and increased T-lymphocyte infiltration. With multiple additional mechanisms of action including upregulation of oxidative stress, depletion of GSH and NADPH, anti-angiogenesis and epigenetic modulation, RRx-001 is being studied as a radio- and chemo-sensitizer to resensitize tumors to prior therapy and to prime tumors to respond to radiation, chemotherapy and immunotherapy in combination therapy studies...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28147265/gender-differences-in-global-but-not-targeted-demethylation-in-ipsc-reprogramming
#15
Inês Milagre, Thomas M Stubbs, Michelle R King, Julia Spindel, Fátima Santos, Felix Krueger, Martin Bachman, Anne Segonds-Pichon, Shankar Balasubramanian, Simon R Andrews, Wendy Dean, Wolf Reik
Global DNA demethylation is an integral part of reprogramming processes in vivo and in vitro, but whether it occurs in the derivation of induced pluripotent stem cells (iPSCs) is not known. Here, we show that iPSC reprogramming involves both global and targeted demethylation, which are separable mechanistically and by their biological outcomes. Cells at intermediate-late stages of reprogramming undergo transient genome-wide demethylation, which is more pronounced in female cells. Global demethylation requires activation-induced cytidine deaminase (AID)-mediated downregulation of UHRF1 protein, and abolishing demethylation leaves thousands of hypermethylated regions in the iPSC genome...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28141798/oxidative-dna-damage-induces-hypomethylation-in-a-compromised-base-excision-repair-colorectal-tumourigenesis
#16
Daniela Furlan, Davide Trapani, Enrico Berrino, Carla Debernardi, Mara Panero, Laura Libera, Nora Sahnane, Cristina Riva, Maria Grazia Tibiletti, Fausto Sessa, Anna Sapino, Tiziana Venesio
BACKGROUND: A compromised base excision repair (BER) promotes carcinogenesis by accumulating oxidative DNA-damaged products as observed in MUTYH-associated polyposis, a hereditary colorectal cancer syndrome marked by adenomas and cancers with an accumulation of 8-oxoguanine. Remarkably, DNA global demethylation has been shown to be mediated by BER, suggesting a relevant interplay with early colorectal tumourigenesis. To check this hypothesis, we investigated a cohort of 49 adenomas and 10 carcinomas, derived from 17 MUTYH-associated polyposis patients; as adenoma controls, we used a set of 36 familial adenomatous polyposis and 24 sporadic polyps...
January 31, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28134679/pathogenic-mechanisms-of-intracellular-bacteria
#17
Hans Helmut Niller, Roland Masa, Annamária Venkei, Sándor Mészáros, Janos Minarovits
PURPOSE OF REVIEW: We wished to overview recent data on a subset of epigenetic changes elicited by intracellular bacteria in human cells. Reprogramming the gene expression pattern of various host cells may facilitate bacterial growth, survival, and spread. RECENT FINDINGS: DNA-(cytosine C5)-methyltransferases of Mycoplasma hyorhinis targeting cytosine-phosphate-guanine (CpG) dinucleotides and a Mycobacterium tuberculosis methyltransferase targeting non-CpG sites methylated the host cell DNA and altered the pattern of gene expression...
January 27, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28132962/increased-expression-of-prion-protein-gene-is-accompanied-by-demethylation-of-cpg-sites-in-a-mouse-embryonal-carcinoma-cell-line-p19c6
#18
Wuyun Dalai, Eiko Matsuo, Natsumi Takeyama, Junichi Kawano, Keiichi Saeki
Elucidation of the processes regulating the prion protein gene (Prnp) is an important key to understanding the development of prion disorders. In this study, we explored the involvement of DNA methylation in Prnp transcriptional regulation during neuronal differentiation of embryonic carcinoma P19C6 cells. When P19C6 cells were differentiated into neuronal cells, the expression of Prnp was markedly increased, while CpG methylation was significantly demethylated at the nucleotide region between -599 and -238 from the transcription start site...
January 28, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28130850/demethylating-and-anti-hepatocarcinogenic-potential-of-hesperidin-a-natural-polyphenol-of-citrus-juices
#19
Zahira Fernández-Bedmar, Jaouad Anter, Angeles Alonso-Moraga, Juana Martín de Las Mulas, Yolanda Millán-Ruiz, Silvia Guil-Luna
Hepatocellular carcinoma (HCC) is a neoplasia representing the fifth most common malignancy worldwide and the third cause of death from cancer. Diets with high content in fruits and vegetables are widely recommended for their health-promoting properties, among them, the protection against diabetes, cancer and cardiovascular diseases. Hesperidin is the most important phenol in the orange fruit with well-known health benefits. Diet components have been used as possible modulator agents of DNA methylation in cancer cells and epigenetic therapy against their harmful effects could be a potential tool in chemotherapy...
January 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28130569/histone-demethylase-utx-counteracts-glucocorticoid-deregulation-of-osteogenesis-by-modulating-histone-dependent-and-independent-pathways
#20
Feng-Sheng Wang, Wei-Shiung Lian, Mel S Lee, Wen-Tsan Weng, Ying-Hsien Huang, Yu-Shan Chen, Yi-Chih Sun, Shing-Long Wu, Pei-Chin Chuang, Jih-Yang Ko
: Excess glucocorticoid administration impairs osteogenic activities, which raises the risk of osteoporotic disorders. Epigenetic methylation of DNA and histone regulates the lineage commitment of progenitor cells. This study was undertaken to delineate the actions of histone lysine demethylase 6a (UTX) with regard to the glucocorticoid impediment of osteogenic differentiation. Osteogenic progenitor cells responded to supraphysiological glucocorticoid by elevating CpG dinucleotide methylation proximal to transcription start sites within Runx2 and osterix promoters and Wnt inhibitor Dickkopf-1 (Dkk1) expression concomitant with low UTX expression...
January 27, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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