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active DNA demethylation

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https://www.readbyqxmd.com/read/28204824/dna-methylation-mediated-caspase-8-downregulation-is-associated-with-anti-apoptotic-activity-and-human-malignant-glioma-grade
#1
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
#2
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
#3
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
#4
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
#5
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/28169463/relationship-between-epigenetic-regulation-dietary-habits-and-the-developmental-origins-of-health-and-disease-theory
#6
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
#7
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
#8
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/28150354/tet1-promotes-cisplatin-resistance-via-demethylating-the-vimentin-promoter-in-ovarian-cancer
#9
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/28149332/the-immunomodulatory-anticancer-agent-rrx-001-induces-an-interferon-response-through-epigenetic-induction-of-viral-mimicry
#10
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
#11
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/28134679/pathogenic-mechanisms-of-intracellular-bacteria
#12
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/28130569/histone-demethylase-utx-counteracts-glucocorticoid-deregulation-of-osteogenesis-by-modulating-histone-dependent-and-independent-pathways
#13
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"
https://www.readbyqxmd.com/read/28130550/control-of-demeter-dna-demethylase-gene-transcription-in-male-and-female-gamete-companion-cells-in-arabidopsis-thaliana
#14
Jin-Sup Park, Jennifer M Frost, Kyunghyuk Park, Hyonhwa Ohr, Guen Tae Park, Seohyun Kim, Hyunjoo Eom, Ilha Lee, Janie S Brooks, Robert L Fischer, Yeonhee Choi
The DEMETER (DME) DNA glycosylase initiates active DNA demethylation via the base-excision repair pathway and is vital for reproduction in Arabidopsis thaliana DME-mediated DNA demethylation is preferentially targeted to small, AT-rich, and nucleosome-depleted euchromatic transposable elements, influencing expression of adjacent genes and leading to imprinting in the endosperm. In the female gametophyte, DME expression and subsequent genome-wide DNA demethylation are confined to the companion cell of the egg, the central cell...
January 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28125731/correlated-5-hydroxymethylcytosine-5hmc-and-gene-expression-profiles-underpin-gene-and-organ-specific-epigenetic-regulation-in-adult-mouse-brain-and-liver
#15
I-Hsuan Lin, Yi-Fan Chen, Ming-Ta Hsu
BACKGROUND: DNA methylation is an epigenetic mechanism essential for gene regulation and vital for mammalian development. 5-hydroxymethylcytosine (5hmC) is the first oxidative product of the TET-mediated 5-methylcytosine (5mC) demethylation pathway. Aside from being a key intermediate in cytosine demethylation, 5hmC may have potential regulatory functions with emerging importance in mammalian biology. METHODS: Here, we investigate the global 5hmC enrichment in five brain structures, including cerebellum, cerebral cortex, hippocampus, hypothalamus and thalamus, as well as liver tissues from female and male adult mice by using chemical capture-based technique coupled with next-generation sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/28125225/dynamics-of-a-dna-mismatch-site-held-in-confinement-discriminate-epigenetic-modifications-of-cytosine
#16
Robert P Johnson, Aaron M Fleming, Rukshan T Perera, Cynthia J Burrows, Henry S White
The identification and discrimination of four epigenetic modifications to cytosine in the proposed active demethylation cycle is demonstrated at the single-molecule level, without the need for chemical pre-treatment or labeling. The wild-type protein nanopore alpha-hemolysin is used to capture individual DNA duplexes containing a single cytosine-cytosine mismatch. The mismatch is held at the latch constriction of alpha-hemolysin, which is used to monitor the kinetics of base flipping at the mismatch site. Base flipping and the subsequent interactions between the DNA and the protein are dramatically altered when one of the cytosine bases is replaced with methyl-, hydroxymethyl-, formyl-, or carboxylcytosine...
January 26, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28115466/loss-of-maternal-trim28-causes-male-predominant-early-embryonic-lethality
#17
Abhishek Sampath Kumar, Michelle K Y Seah, Ka Yi Ling, Yaju Wang, Joel H L Tan, Sandra Nitsch, Shu Ly Lim, Chanchao Lorthongpanich, Heike Wollmann, Diana H P Low, Ernesto Guccione, Daniel M Messerschmidt
Global DNA demethylation is a hallmark of embryonic epigenetic reprogramming. However, embryos engage noncanonical DNA methylation maintenance mechanisms to ensure inheritance of exceptional epigenetic germline features to the soma. Besides the paradigmatic genomic imprints, these exceptions remain ill-defined, and the mechanisms ensuring demethylation resistance in the light of global reprogramming remain poorly understood. Here we show that the Y-linked gene Rbmy1a1 is highly methylated in mature sperm and resists DNA demethylation post-fertilization...
January 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28115210/the-methylation-of-nuclear-and-mitochondrial-dna-in-ageing-phenotypes-and-longevity
#18
REVIEW
Maria Giulia Bacalini, Patrizia D'Aquila, Elena Marasco, Christine Nardini, Alberto Montesanto, Claudio Franceschi, Giuseppe Passarino, Paolo Garagnani, Dina Bellizzi
An increasing body of data is progressively indicating that the comprehension of the epigenetic landscape, actively integrated with the genetic elements, is crucial to delineate the molecular basis of the inter-individual complexity of ageing process. Indeed, it has emerged that DNA methylation changes occur during ageing, consisting mainly in a progressive process of genome demethylation, in a hypermethylation of gene-specific CpG dinucleotides, as well as in an inter-individual divergence of the epigenome due to stochastic events and environmental exposures throughout life, namely as epigenetic drift...
January 20, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28108626/a-new-role-for-er%C3%AE-silencing-via-dna-methylation-of-basal-stem-cell-and-emt-genes
#19
Eric A Ariazi, John C Taylor, Michael A Black, Emmanuelle Nicolas, Michael J Slifker, Diana J Azzam, Jeff Boyd
: Resistance to hormonal therapies is a major clinical problem in the treatment of estrogen receptor α-positive (ERα(+)) breast cancers. Epigenetic marks, namely DNA methylation of cytosine at specific CpG sites (5mCpG), are frequently associated with ERα(+) status in human breast cancers. Therefore, ERα may regulate gene expression in part via DNA methylation. This hypothesis was evaluated using a panel of breast cancer cell line models of antiestrogen resistance. Microarray gene expression profiling was used to identify genes normally silenced in ERα(+) cells but derepressed upon exposure to the demethylating agent decitabine, derepressed upon long-term loss of ERα expression, and resuppressed by gain of ERα activity/expression...
February 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28100749/promoted-interaction-of-c-ebp%C3%AE-with-demethylated-cxcr3-gene-promoter-contributes-to-neuropathic-pain-in-mice
#20
Bao-Chun Jiang, Li-Na He, Xiao-Bo Wu, Hui Shi, Wen-Wen Zhang, Zhi-Jun Zhang, De-Li Cao, Chun-Hua Li, Jun Gu, Yong-Jing Gao
: DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes regulated by DNA methylation under neuropathic pain condition remain largely unknown. Here we investigated how chemokine receptor CXCR3 is regulated by DNA methylation and how it contributes to neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased Cxcr3 mRNA and protein expression in the neurons of the spinal cord. Meanwhile, the CpG (5'-cytosine-phosphate-guanine-3') island in the Cxcr3 gene promoter region was demethylated, and the expression of DNA methyltransferase 3b (DNMT3b) was decreased...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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