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active DNA demethylation

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https://www.readbyqxmd.com/read/28916527/demethylation-therapy-as-a-targeted-treatment-for-human-papilloma-virus-associated-head-and-neck-cancer
#1
Asel K Biktasova, Michael Hajek, Andrew B Sewell, Cyril S Gary, Gary Bellinger, Hari Deshpande, Aarti K Bhatia, Barbara A Burtness, Benjamin L Judson, Saral Mehra, Wendell G Yarbrough, Natalia Issaeva
PURPOSE: DNA methylation in human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) may have importance for continuous expression of HPV oncogenes, tumor cell proliferation and survival. Here, we determined activity of a global DNA demethylating agent, 5-azacytidine (5-aza), against HPV+ HNSCC in pre-clinical models and explored it as a targeted therapy in a window trial enrolling patients with HPV+ HNSCC. EXPERIMENTAL DESIGN: Sensitivity of HNSCC cells to 5-aza treatment was determined, then 5-aza activity was tested in vivo using xenografted tumors in a mouse model...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28911331/dynamic-dna-methylation-reconfiguration-during-seed-development-and-germination
#2
Taiji Kawakatsu, Joseph R Nery, Rosa Castanon, Joseph R Ecker
BACKGROUND: Unlike animals, plants can pause their life cycle as dormant seeds. In both plants and animals, DNA methylation is involved in the regulation of gene expression and genome integrity. In animals, reprogramming erases and re-establishes DNA methylation during development. However, knowledge of reprogramming or reconfiguration in plants has been limited to pollen and the central cell. To better understand epigenetic reconfiguration in the embryo, which forms the plant body, we compared time-series methylomes of dry and germinating seeds to publicly available seed development methylomes...
September 15, 2017: Genome Biology
https://www.readbyqxmd.com/read/28911330/extensive-transcriptomic-and-epigenomic-remodelling-occurs-during-arabidopsis-thaliana-germination
#3
Reena Narsai, Quentin Gouil, David Secco, Akanksha Srivastava, Yuliya V Karpievitch, Lim Chee Liew, Ryan Lister, Mathew G Lewsey, James Whelan
BACKGROUND: Seed germination involves progression from complete metabolic dormancy to a highly active, growing seedling. Many factors regulate germination and these interact extensively, forming a complex network of inputs that control the seed-to-seedling transition. Our understanding of the direct regulation of gene expression and the dynamic changes in the epigenome and small RNAs during germination is limited. The interactions between genome, transcriptome and epigenome must be revealed in order to identify the regulatory mechanisms that control seed germination...
September 15, 2017: Genome Biology
https://www.readbyqxmd.com/read/28901965/anaplastic-gliomas-in-adults-an-update
#4
Cristina Izquierdo, Bastien Joubert, François Ducray
PURPOSE OF REVIEW: The current review summarizes recent advances on the oncogenesis, classification and treatment of adult anaplastic gliomas. RECENT FINDINGS: According to the 2016 WHO classification, three main molecular subgroups of adult diffuse anaplastic gliomas can be distinguished based on the 1p/19q codeletion and isocitrate dehydrogenase (IDH) mutation status. In the future, this classification may be further refined based on the telomerase reverse transcriptase promoter and alpha thalassemia/mental retardation syndrome X-linked mutation status, gene expression, DNA methylation and genomic profiling...
September 8, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28899881/tet1-overexpression-leads-to-anxiety-like-behavior-and-enhanced-fear-memories-via-the-activation-of-calcium-dependent-cascade-through-egr1-expression-in-mice
#5
Wookbong Kwon, Hyeng-Soo Kim, Jain Jeong, Yonghun Sung, Minjee Choi, Song Park, Jinhee Lee, Soyoung Jang, Sung Hyun Kim, Sanggyu Lee, Myoung Ok Kim, Zae Young Ryoo
Ten-eleven translocation methylcytosine dioxygenase 1 (Tet1) initiates DNA demethylation by converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) at CpG-rich regions of genes, which have key roles in adult neurogenesis and memory. In addition, the overexpression of Tet1 with 5-hmC alteration in patients with psychosis has also been reported, for instance in schizophrenia and bipolar disorders. The mechanism underlying Tet1 overexpression in the brain; however, is still elusive. In the present study, we found that Tet1-transgenic (Tet1-TG) mice displayed abnormal behaviors involving elevated anxiety and enhanced fear memories...
September 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28894455/dna-demethylase-regulated-genes-show-methylation-independent-spatiotemporal-expression-patterns
#6
Ulrike Schumann, Joanne Lee, Kemal Kazan, Michael Ayliffe, Ming-Bo Wang
Recent research has indicated that a subset of defense-related genes is downregulated in the Arabidopsis DNA demethylase triple mutant rdd (ros1 dml2 dml3) resulting in increased susceptibility to the fungal pathogen Fusarium oxysporum. In rdd plants these downregulated genes contain hypermethylated transposable element sequences (TE) in their promoters, suggesting that this methylation represses gene expression in the mutant and that these sequences are actively demethylated in wild-type plants to maintain gene expression...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28894047/the-role-of-vitamin-c-in-epigenetic-regulation
#7
Jolanta Guz, Ryszard Oliński
Vitamin C (L-ascorbic acid) is a micronutrient best known for its anti-scurvy activity in humans. Vitamin C is involved in many biological processes involving enzymatic reactions that are catalyzed by members of dioxygenases which use Fe(II) and 2-oxoglutarate as a co-substrate.The article reviews recent data that suggest the involvement of ascorbate in dioxygenases catalyzed chromatin and DNA modifications which thereby contribute to epigenetic regulation. Concerning chromatin modification, the dioxygenases are involved in distinct demethylation reactions with varying specificity for the position of the lysine on the target histone...
August 24, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28892104/synergistic-anti-aml-effects-of-the-lsd1-inhibitor-t-3775440-and-the-nedd8-activating-enzyme-inhibitor-pevonedistat-via-transdifferentiation-and-dna-rereplication
#8
Y Ishikawa, K Nakayama, M Morimoto, A Mizutani, A Nakayama, K Toyoshima, A Hayashi, S Takagi, R Dairiki, H Miyashita, S Matsumoto, K Gamo, T Nomura, K Nakamura
Lysine-specific demethylase 1A (LSD1, KDM1A) specifically demethylates di- and monomethylated histones H3K4 and K9, resulting in context-dependent transcriptional repression or activation. We previously identified an irreversible LSD1 inhibitor T-3775440, which exerts antileukemic activities in a subset of acute myeloid leukemia (AML) cell lines by inducing cell transdifferentiation. The NEDD8-activating enzyme inhibitor pevonedistat (MLN4924, TAK-924) is an investigational drug with antiproliferative activities in AML, and is also reported to induce cell differentiation...
September 11, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28887159/integrative-analysis-of-dna-methylation-and-mrna-expression-during-differentiation-of-umbilical-cord-blood-derived-mononuclear-cells-to-endothelial-cells
#9
Yoonjeong Jeong, Yukyung Jun, Jihye Kim, Hyojin Park, Kyu-Sung Choi, Haiying Zhang, Jeong Ae Park, Ja-Young Kwon, Young-Myeong Kim, Sanghyuk Lee, Young-Guen Kwon
Differentiation of umbilical cord blood derived mononuclear cells to endothelial cells is accompanied by massive changes in gene expression. Although methylation and demethylation of DNA likely play crucial roles in regulating gene expression, their interplay during differentiation remains elusive. To address this question, we performed deep sequencing of DNA methylation and mRNA expression to profile global changes in promoter methylation and gene expression during differentiation from mononuclear cells to outgrowing cells...
September 5, 2017: Gene
https://www.readbyqxmd.com/read/28872903/in-vitro-biological-effects-of-sulforaphane-sfn-epigallocatechin-3-gallate-egcg-and-curcumin-on-breast-cancer-cells-a-systematic-review-of-the-literature
#10
Vincenza Gianfredi, Daniele Nucci, Samuele Vannini, Milena Villarini, Massimo Moretti
Much of the recent research in neoplasia has been focusing on the epigenetics of cancer cells, particularly as regards the search for potential molecular biomarkers that could be used for early diagnosis, effective treatment, and prognosis of several types of cancer. Carcinogenesis often starts with mutations in oncogenes and tumor suppressor genes, and it leads to anomalies in cellular processes as vital as cell cycle regulation and apoptosis. Because malignant changes arise as a result of genetic as well as epigenetic mechanisms, one possible means of intervention involves reprogramming gene expression, so as to-at least in part-revert the molecular alterations...
September 5, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28870782/the-role-of-tet-mediated-dna-hydroxymethylation-in-prostate-cancer
#11
E Smeets, A G Lynch, S Prekovic, T Van den Broeck, L Moris, C Helsen, S Joniau, F Claessens, C E Massie
Ten-eleven translocation (TET) proteins are recently characterized dioxygenases that regulate demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine and further derivatives. The recent finding that 5hmC is also a stable and independent epigenetic modification indicates that these proteins play an important role in diverse physiological and pathological processes such as neural and tumor development. Both the genomic distribution of (hydroxy)methylation and the expression and activity of TET proteins are dysregulated in a wide range of cancers including prostate cancer...
September 1, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28869603/a-regulatory-circuit-composed-of-dna-methyltransferases-and-receptor-tyrosine-kinases-controls-lung-cancer-cell-aggressiveness
#12
F Yan, N Shen, J Pang, N Zhao, B Deng, B Li, Y Yang, P Yang, J R Molina, S Liu
Overexpression of DNMT1 and KIT is prevalent in lung cancer, yet the underlying molecular mechanisms are poorly understood. While the deregulated activation of DNMT1 or KIT has been implicated in lung cancer pathogenesis, whether and how DNMT1 and KIT orchestrate lung tumorigenesis are unclear. Here, using human lung cancer tissue microarrays and fresh frozen tissues, we found that the overexpression of DNMT1 is positively correlated with the upregulation of KIT in tumor tissues. We demonstrated that DNMT1 and KIT form a positive regulatory loop, in which ectopic DNMT1 expression increases, whereas targeted DNMT1 depletion abrogates KIT signaling cascade through Sp1/miR-29b network...
September 4, 2017: Oncogene
https://www.readbyqxmd.com/read/28863210/alternatively-spliced-mefv-transcript-lacking-exon-2-and-its-protein-isoform-pyrin-2d-implies-an-epigenetic-regulation-of-the-gene-in-inflammatory-cell-culture-models
#13
Gokce Celikyapi Erdem, Sule Erdemir, Irem Abaci, Asli K Kirectepe Aydin, Elif Everest, Eda Tahir Turanli
The function of gene body DNA methylation in alternative splicing, and its relation to disease pathogenesis is not fully elucidated. The gene for familial Mediterranean fever (MEFV) encodes the pyrin protein and contains a 998 bp CpG island, covering the second exon, which is differentially methylated in FMF patients compared to healthy controls. Our further observation of increased exon 2-spliced MEFV transcript in leukocytes of FMF patients provoked us to test the role of exon methylation in alternative splicing using inflammatory cell culture models...
July 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28842406/vitamin-c-restores-tet2-activity-in-tet2-deficient-leukemia
#14
(no author information available yet)
TET2 restoration promotes DNA demethylation and differentiation to suppress leukemic progression.
August 25, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28836260/hyperhomocysteinemia-and-vascular-injury-the-advance-of-mechanisms-and-drug-targets
#15
REVIEW
Yi Fu, Xian Wang, Wei Kong
Homocysteine (Hcy) is a sulphur-containing non-proteinogenic amino acid. Hyperhomocysteinemia (HHcy), the pathogenic elevation of plasma Hcy as a result of an imbalance of Hcy metabolism, is an independent risk factor for various vascular diseases, such as atherosclerosis, hypertension, vascular calcification, and aneurysm. Hcy-lowering therapy via dietary supplementation with folic acids and vitamin B exhibits a stronger effect on vascular disease prevention in regions in which the population has a low folate consumption than in areas exposed to folate fortification...
August 24, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28834755/zscan4-inhibits-maintenance-dna-methylation-to-facilitate-telomere-elongation-in-mouse-embryonic-stem-cells
#16
Jiameng Dan, Philippe Rousseau, Swanand Hardikar, Nicolas Veland, Jiemin Wong, Chantal Autexier, Taiping Chen
Proper telomere length is essential for embryonic stem cell (ESC) self-renewal and pluripotency. Mouse ESCs (mESCs) sporadically convert to a transient totipotent state similar to that of two-cell (2C) embryos to recover shortened telomeres. Zscan4, which exhibits a burst of expression in 2C-like mESCs, is required for telomere extension in these cells. However, the mechanism by which Zscan4 extends telomeres remains elusive. Here, we show that Zscan4 facilitates telomere elongation by inducing global DNA demethylation through downregulation of Uhrf1 and Dnmt1, major components of the maintenance DNA methylation machinery...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28831075/demeter-plant-dna-demethylase-induces-antiviral-response-by-interferon-signalling-in-animal-cells
#17
Young Geun Mok, Ki Young Choi, Seung Hwan Hong, Jin Hoe Huh
DNA methylation is a prominent epigenetic modification in plants and animals regulated by similar mechanisms but the process of DNA demethylation is profoundly different. Unlike vertebrates that require a series of enzymatic conversions of 5-methylcytosine (5mC) into other bases for DNA demethylation, plants utilize the DEMETER (DME) family of 5mC DNA glycosylases to catalyze a direct removal of 5mC from DNA. Here we introduced Arabidopsis DME into human HEK-293T cells to allow direct 5mC excision, and observed that direct DNA demethylation activity was successfully implemented by DME expression...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28827588/nei-like-1-neil1-excises-5-carboxylcytosine-directly-and-stimulates-tdg-mediated-5-formyl-and-5-carboxylcytosine-excision
#18
Anton Slyvka, Karolina Mierzejewska, Matthias Bochtler
Thymine DNA glycosylase (TDG) and Nei-like 1 (NEIL1) have both been implicated in the base excision repair step of active DNA demethylation. The robust glycosylase activity of TDG on DNA substrates containing 5-formylcytosine (5fC) or 5-carboxylcytosine (5caC) is universally accepted, but the mode of action of NEIL1 is still debated. Based on genetic experiments, it has been suggested that NEIL1 acts redundantly with TDG and excises 5fC and 5caC directly. However, this result has been disputed, and it was suggested instead that NEIL1 is recruited by the monofunctional TDG for the 2'-deoxyribose excision step...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811542/identification-replication-and-characterization-of-epigenetic-remodelling-in-the-aging-genome-a-cross-population-analysis
#19
Shuxia Li, Lene Christiansen, Kaare Christensen, Torben A Kruse, Paul Redmond, Riccardo E Marioni, Ian J Deary, Qihua Tan
Aging is a complex biological process regulated by multiple cellular pathways and molecular mechanisms including epigenetics. Using genome-wide DNA methylation data measured in a large collection of Scottish old individuals, we performed discovery association analysis to identify age-methylated CpGs and replicated them in two independent Danish cohorts. The double-replicated CpGs were characterized by distribution over gene regions and location in relation to CpG islands. The replicated CpGs were further characterized by involvement in biological pathways to study their functional implications in aging...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807729/cpg-demethylation-in-the-neurotoxicity-of-1-methyl-4-phenylpyridinium-might-mediate-transcriptional-up-regulation-of-%C3%AE-synuclein-in-sh-sy5y-cells
#20
Jian Yang, Zhaofei Yang, Xuan Wang, Min Sun, Yong Wang, Xiaomin Wang
The accumulation of α-synuclein is the primary pathological hallmark of Parkinson's disease (PD). In PD patients, CpG demethylation of intron-1 has been reported to be associated with α-synuclein up-regulation. Environmental factor, for example neurotoxin, is a major etiological risk factor in PD pathogenesis. However, the role of CpG methylation in neurotoxin-induced PD has not been addressed completely yet. To explore CpG methylation associating with α-synuclein transcription and its underlying mechanisms in the neurotoxin-induced PD pathology, human neuroblastoma SH-SY5Y cells were treated with neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP(+))...
August 12, 2017: Neuroscience Letters
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