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5 hydroxymethylcytosine

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https://www.readbyqxmd.com/read/28623268/ascorbate-induces-apoptosis-in-melanoma-cells-by-suppressing-clusterin-expression
#1
Sushmita Mustafi, David W Sant, Zhao-Jun Liu, Gaofeng Wang
Pharmacological levels of ascorbate have long been suggested as a potential treatment of cancer. However, we observed that EC50 of ascorbate was at a similar level for cultured healthy melanocytes and melanoma cells, suggesting a limit of pharmacological ascorbate in treating cancer. Loss of 5-hydroxymethylcytosine (5 hmC) is an epigenetic hallmark of cancer and ascorbate promotes 5 hmC generation by serving as a cofactor for TET methylcytosine dioxygenases. Our previous work demonstrated that ascorbate treatment at physiological level (100 μM) increased 5 hmC content in melanoma cells toward the level of healthy melanocytes...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621264/dna-methylation-hydroxymethylation-in-melanoma
#2
REVIEW
Siqi Fu, Haijing Wu, Huiming Zhang, Christine G Lian, Qianjin Lu
Melanoma is a malignant tumor of melanocytes and is considered to be the most aggressive cancer among all skin diseases. The pathogenesis of melanoma has not been well documented, which may restrict the research and development of biomarkers and therapies. To date, several genetic and epigenetic factors have been identified as contributing to the development and progression of melanoma. Besides the findings on genetic susceptibilities, the recent progress in epigenetic studies has revealed that loss of the DNA hydroxymethylation mark, 5-hydroxymethylcytosine (5-hmC), along with high levels of DNA methylation at promoter regions of several tumor suppressor genes in melanoma, may serve as biomarkers for melanoma...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611311/genome-wide-5-hydroxymethylcytosine-patterns-in-human-spermatogenesis-are-associated-with-semen-quality
#3
Olga A Efimova, Anna A Pendina, Andrei V Tikhonov, Sergey E Parfenyev, Irina D Mekina, Evgeniia M Komarova, Mariia A Mazilina, Eugene V Daev, Olga G Chiryaeva, Ilona A Galembo, Mikhail I Krapivin, Oleg S Glotov, Irina S Stepanova, Svetlana A Shlykova, Igor Yu. Kogan, Alexander M Gzgzyan, Tatyana V Kuznetzova, Vladislav S Baranov
We performed immunofluorescent analysis of DNA hydroxymethylation and methylation in human testicular spermatogenic cells from azoospermic patients and ejaculated spermatozoa from sperm donors and patients from infertile couples. In contrast to methylation which was present throughout spermatogenesis, hydroxymethylation was either high or almost undetectable in both spermatogenic cells and ejaculated spermatozoa. On testicular cytogenetic preparations, 5-hydroxymethylcytosine was undetectable in mitotic and meiotic chromosomes, and was present exclusively in interphase spermatogonia Ad and in a minor spermatid population...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28601635/silencing-hif-1%C3%AE-induces-tet2-expression-and-augments-ascorbic-acid-induced-5-hydroxymethylation-of-dna-in-human-metastatic-melanoma-cells
#4
Adam P Fischer, Sarah L Miles
Expression and function of Ten-eleven translocation (TET) enzymes, which initiate DNA demethylation by catalyzing the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (5 hmC) on methylated DNA, are frequently lost in malignant tissue. This ultimately results in lost expression of methylated tumor suppressor genes. Many malignancies, including melanoma, also aberrantly overexpress the oncogenic hypoxia inducible factor-1α (HIF-1α) transcription factor, however the association between HIF-1α and TET enzyme expression is largely uninvestigated...
June 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28584398/tumor-necrosis-factor-%C3%AE-decreases-ec-sod-expression-through-dna-methylation
#5
Shunpei Morisawa, Hiroyuki Yasuda, Tetsuro Kamiya, Hirokazu Hara, Tetsuo Adachi
Extracellular-superoxide dismutase (EC-SOD) is a secreted antioxidative enzyme, and its presence in vascular walls may play an important role in protecting the vascular system against oxidative stress. EC-SOD expression in cultured cell lines is regulated by various cytokines including tumor necrosis factor-α (TNF-α). TNF-α is a major mediator of pathophysiological conditions and may induce or suppress the generation of various types of mediators. Epigenetics have been defined as mitotically heritable changes in gene expression that do not affect the DNA sequence, and include DNA methylation and histone modifications...
May 2017: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/28582417/genome-wide-alteration-in-dna-hydroxymethylation-in-the-sperm-from-bisphenol-a-exposed-men
#6
Huajun Zheng, Xiaoyu Zhou, De-Kun Li, Fen Yang, Hongjie Pan, Tianqi Li, Maohua Miao, Runsheng Li, Wei Yuan
Environmental BPA exposure has been shown to impact human sperm concentration and motility, as well as rodent spermatogenesis. However, it is unclear whether BPA exposure is associated with alteration in DNA hydroxymethylation, a marker for epigenetic modification, in human sperm. A genome-wide DNA hydroxymethylation study was performed using sperm samples of men who were occupationally exposed to BPA. Compared with controls who had no occupational BPA exposure, the total levels of 5-hydroxymethylcytosine (5hmc) increased significantly (19...
2017: PloS One
https://www.readbyqxmd.com/read/28555658/tet-mediated-active-dna-demethylation-mechanism-function-and-beyond
#7
REVIEW
Xiaoji Wu, Yi Zhang
In mammals, DNA methylation in the form of 5-methylcytosine (5mC) can be actively reversed to unmodified cytosine (C) through TET dioxygenase-mediated oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), followed by replication-dependent dilution or thymine DNA glycosylase (TDG)-dependent base excision repair. In the past few years, biochemical and structural studies have revealed mechanistic insights into how TET and TDG mediate active DNA demethylation...
May 30, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28554766/the-level-and-clinical-significance-of-5-hydroxymethylcytosine-in-oral-squamous-cell-carcinoma-an-immunohistochemical-study-in-95-patients
#8
Yi Wang, Huijun Hu, Qiong Wang, Zhongwu Li, Yumin Zhu, Wei Zhang, Yanling Wang, Hongbing Jiang, Jie Cheng
Accumulating evidence has revealed that aberrant abundance of 5-hydroxymethylcytosine (5hmC) is critically involved in tumorigenesis. The aim of the present study was to investigate the level of 5hmC in primary oral squamous cell carcinoma (OSCC) and determine its clinical significance as well as prognostic value in predicting patients' outcomes. The expression levels of 5hmC in 95 human OSCC samples and 24 normal oral mucosa were evaluated by immunohistochemical staining. Moreover, the associations between the expression status of 5hmC and several clinicopathological parameters as well as patients' survival were further statistically assessed...
April 19, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28531272/a-novel-isoform-of-tet1-that-lacks-a-cxxc-domain-is-overexpressed-in-cancer
#9
Charly R Good, Jozef Madzo, Bela Patel, Shinji Maegawa, Nora Engel, Jaroslav Jelinek, Jean-Pierre J Issa
TET1 oxidizes methylated cytosine into 5-hydroxymethylcytosine (5hmC), resulting in regulation of DNA methylation and gene expression. Full length TET1 (TET1FL) has a CXXC domain that binds to unmethylated CpG islands (CGIs). This CXXC domain allows TET1 to protect CGIs from aberrant methylation, but it also limits its ability to regulate genes outside of CGIs. Here, we report a novel isoform of TET1 (TET1ALT) that has a unique transcription start site from an alternate promoter in intron 2, yielding a protein with a unique translation start site...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28529766/genome-wide-profiling-of-dna-5-hydroxymethylcytosine-during-rat-sertoli-cell-maturation
#10
Miriam Landfors, Jostein Johansen, Jan Magnus Aronsen, Cathrine Broberg Vågbø, Louis C Doré, Chuan He, Ivar Sjaastad, Pål Sætrom, Péter Fedorcsák, John Arne Dahl, Håvard Aanes, Markus Fußer, Arne Klungland
Sertoli cells have dual roles during the cells' lifetime. In the juvenile mammal, Sertoli cells proliferate and create the structure of the testis, and during puberty they cease to proliferate and take on the adult role of supporting germ cells through spermatogenesis. Accordingly, many genes expressed in Sertoli cells during testis formation are repressed during spermatogenesis. 5-Hydroxymethylcytosine (5hmC) is a DNA modification enzymatically generated from 5mC and present in all investigated mammalian tissues at varying levels...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28529475/fragile-x-associated-tremor-ataxia-syndrome-from-molecular-pathogenesis-to-development-of-therapeutics
#11
REVIEW
Ha Eun Kong, Juan Zhao, Shunliang Xu, Peng Jin, Yan Jin
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a premutation CGG repeat expansion (55-200 repeats) within the 5' UTR of the fragile X gene (FMR1). FXTAS is characterized by intension tremor, cerebellar ataxia, progressive neurodegeneration, parkinsonism and cognitive decline. The development of transgenic mouse and Drosophila melanogaster models carrying an expanded CGG repeat has yielded valuable insight into the pathophysiology of FXTAS. To date, we know of two main molecular mechanisms of this disorder: (1) a toxic gain of function of the expanded CGG-repeat FMR1 mRNA, which results in the binding/sequestration of the CGG-binding proteins; and (2) CGG repeat-associated non-AUG-initiated (RAN) translation, which generates a polyglycine peptide toxic to cells...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28520399/immunofluorescence-imaging-strategy-for-evaluation-of-the-accessibility-of-dna-5-hydroxymethylcytosine-in-chromatins
#12
Shangwei Zhong, Zhe Li, Ting Jiang, Xiangjun Li, Hailin Wang
DNA 5-hydroxymethylcytosine (5hmC) is an important epigenetic modification found in various mammalian cells. Immunofluorescence imaging analysis essentially provides visual pictures for the abundance and distribution of DNA 5hmC in single cells. However, nuclear DNA is usually wrapped around nucleosomes, packaged into chromatins, and further bound with many functional proteins. These physiologically relevant events would generate barriers to the anti-5hmC antibody to selectively recognize 5hmC in DNA. By taking advantage of these naturally generated barriers, here, we present a strategy to evaluate the accessibility of DNA 5hmC in chromatins in situ...
June 6, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28513825/loss-of-tet1-facilitates-dld1-colon-cancer-cell-migration-via-h3k27me3-mediated-down-regulation-of-e-cadherin
#13
Zhen Zhou, Hong-Sheng Zhang, Yang Liu, Zhong-Guo Zhang, Guang-Yuan Du, Hu Li, Xiao-Ying Yu, Ying-Hui Huang
Epigenetic modifications such as histone modifications and cytosine hydroxymethylation are linked to tumorigenesis. Loss of 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation 1 (TET1) down-regulation facilitates tumor initiation and development. However, the mechanisms by which loss of TET1 knockdown promotes malignancy development remains unclear. Here, we report that TET1 knockdown induced epithelial-mesenchymal transition (EMT) and increased cancer cell growth, migration and invasion in DLD1 cells...
May 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28505334/direction-a-machine-learning-framework-for-predicting-and-characterizing-dna-methylation-and-hydroxymethylation-in-mammalian-genomes
#14
Milos Pavlovic, Pradipta Ray, Kristina Pavlovic, Aaron Kotamarti, Min Chen, Michael Q Zhang
Motivation: 5-Methylcytosine and 5-Hydroxymethylcytosine in DNA are major epigenetic modifications known to significantly alter mammalian gene expression. High-throughput assays to detect these modifications are expensive, labor-intensive, unfeasible in some contexts, and leave a portion of the genome unqueried. Hence, we devised a novel, supervised, integrative learning framework to perform whole-genome methylation and hydroxymethylation predictions in CpG dinucleotides. Our framework can also perform imputation of missing or low quality data in existing sequencing datasets...
May 12, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28501209/a-sensitive-signal-off-electrogenerated-chemiluminescence-biosensing-method-for-the-discrimination-of-dna-hydroxymethylation-based-on-glycosylation-modification-and-signal-quenching-from-ferroceneboronic-acid
#15
Yuling Zhang, Yan Li, Yingying Wei, Huiping Sun, Huan Wang
In this study, a new and sensitive signal-off electrogenerated chemiluminescence (ECL) biosensing method for the quantification of 5-hydroxymethylcytosine in DNA (5-hmC-DNA) was developed. The method achieved simple and sensitive detection of 5-hmC-DNA based on the glycosylation of 5-hmC, combining both the amplification function of gold nanoparticles (AuNPs) and the high quenching efficiency of the tris(2, 2'-ripyridine) dichlororuthenium(II) (Ru(bpy)3(2+))-ferrocene (Fc) system. First, the electrode modified with a mixture of Nafion and AuNPs was utilized as the platform for electrostatically adsorbing Ru(bpy)3(2+)(an ECL-emitting species) and assembling 5-hmC-DNA...
August 1, 2017: Talanta
https://www.readbyqxmd.com/read/28499883/the-role-of-5-hydroxymethylcytosine-in-development-aging-and-age-related-diseases
#16
REVIEW
V López, A F Fernández, M F Fraga
DNA methylation at the fifth position of cytosines (5mC) represents a major epigenetic modification in mammals. The recent discovery of 5-hydroxymethylcytosine (5hmC), resulting from 5mC oxidation, is redefining our view of the epigenome, as multiple studies indicate that 5hmC is not simply an intermediate of DNA demethylation, but a genuine epigenetic mark that may play an important functional role in gene regulation. Currently, the availability of platforms that discriminates between the presence of 5mC and 5hmC at single-base resolution is starting to shed light on the functions of 5hmC...
May 10, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28497329/effect-of-cadmium-on-cytosine-hydroxymethylation-in-gastropod-hepatopancreas
#17
Dragos Nica, Cristina Popescu, George Draghici, Ionela Privistirescu, Maria Suciu, Reinhard Stöger
5-Hydroxymethylcytosine (5hmC) is an important, yet poorly understood epigenetic DNA modification, especially in invertebrates. Aberrant genome-wide 5hmC levels have been associated with cadmium (Cd) exposure in humans, but such information is lacking for invertebrate bioindicators. Here, we aimed to determine whether this epigenetic mark is present in DNA of the hepatopancreas of the land snail Cantareus aspersus and is responsive to Cd exposure. Adult snails were reared under laboratory conditions and exposed to graded amounts of dietary cadmium for 14 days...
June 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28492666/dna-friendly-cu-ii-tempo-catalyzed-5-hydroxymethylcytosine-specific-oxidation
#18
Taku Matsushita, Yuya Moriyama, Genta Nagae, Hiroyuki Aburatani, Akimitsu Okamoto
The mixture of copper(ii) perchlorate and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) mildly and specifically oxidized 5-hydroxymethylcytosine to yield 5-formylcytosine because of its allyl alcohol specificity. The genomic DNA oxidized at 5-hydroxymethylcytosine by the copper(ii)/TEMPO oxidation was efficiently analyzed using various practical methods: DNA cleavage by piperidine, specific functionalization by hydrazone formation, and genome-wide high-resolution microarray.
May 11, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28485726/gene-body-5-hydroxymethylation-is-associated-with-gene-expression-changes-in-the-prefrontal-cortex-of-depressed-individuals
#19
J A Gross, A Pacis, G G Chen, M Drupals, P-E Lutz, L B Barreiro, G Turecki
5-Hydroxymethylcytosine (5hmC) is a recently characterized epigenetic mark that is particularly abundant in brain tissue and that regulates gene transcription. We have recently begun to understand the important role of 5hmC in brain development, plasticity and disease, but there are currently little data on 5hmC alterations in psychiatric illnesses. Here we report what we believe to be the first genome-wide analysis of 5hmC in the depressed brain. Using AbaSI sequencing, we investigated 5hmC in the prefrontal cortex of depressed (N=19) and psychiatrically healthy controls (N=19)...
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28484589/idh1-or-2-mutations-do-not-predict-outcome-and-do-not-cause-loss-of-5-hydroxymethylcytosine-or-altered-histone-modifications-in-central-chondrosarcomas
#20
Arjen H G Cleven, Johnny Suijker, Georgios Agrogiannis, Inge H Briaire-de Bruijn, Norma Frizzell, Attje S Hoekstra, Pauline M Wijers-Koster, Anne-Marie Cleton-Jansen, Judith V M G Bovée
BACKGROUND: Mutations in isocitrate dehydrogenase (IDH)1 or -2 are found in ~50% of conventional central chondrosarcomas and in up to 87% of their assumed benign precursors enchondromas. The mutant enzyme acquires the activity to convert α-ketoglutarate into the oncometabolite d-2-hydroxyglutarate (d-2-HG), which competitively inhibits α-ketoglutarate dependent enzymes such as histone- and DNA demethylases. METHODS: We therefore evaluated the effect of IDH1 or -2 mutations on histone modifications (H3K4me3, H3K9me3 and H3K27me3), chromatin remodeler ATRX expression, DNA modifications (5-hmC and 5-mC), and TET1 subcellular localization in a genotyped cohort (IDH, succinate dehydrogenase (SDH) and fumarate hydratase (FH)) of enchondromas and central chondrosarcomas (n = 101) using immunohistochemistry...
2017: Clinical Sarcoma Research
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