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https://www.readbyqxmd.com/read/28661477/microrna-29a-induces-loss-of-5-hydroxymethylcytosine-and-promotes-metastasis-of-hepatocellular-carcinoma-through-a-tet-socs1-mmp9-signaling-axis
#1
Qing Chen, Dan Yin, Yong Zhang, Lei Yu, Xue-Dong Li, Zheng-Jun Zhou, Shao-Lai Zhou, Dong-Mei Gao, Jie Hu, Cheng Jin, Zheng Wang, Ying-Hong Shi, Ya Cao, Jia Fan, Zhi Dai, Jian Zhou
Ten eleven translocation (TET) enzymes convert 5-methylcytosine (5-mC) to 5-hydroxy-methylcytosine (5-hmC) and have crucial roles in biological and pathological processes by mediating DNA demethylation, however, the functional role of this epigenetic mark and the related enzymes in hepatocellular carcinoma (HCC) progression remains unknown. Here, we demonstrated that TET-family enzymes downregulation was one likely mechanism underlying 5-hmC loss in HCC. We found that miR-29a overexpression increased DNA methylation of suppressor of cytokine signaling 1 (SOCS1) promoter was associated with HCC metastasis in vitro and in vivo...
June 29, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28634398/mutations-in-human-aid-differentially-affect-its-ability-to-deaminate-cytidine-and-5-methylcytidine-in-ssdna-substrates-in-vitro
#2
Lucyna Budzko, Paulina Jackowiak, Karol Kamel, Joanna Sarzynska, Janusz M Bujnicki, Marek Figlerowicz
Activation-induced cytidine deaminase (AID) is known for its established role in antibody production. AID induces the diversification of antibodies by deaminating deoxycytidine (C) within immunoglobulin genes. The capacity of AID to deaminate 5-methyldeoxycytidine (5 mC) and/or 5-hydroxymethyldeoxycytidine (5 hmC), and consequently AID involvement in active DNA demethylation, is not fully resolved. For instance, structural determinants of AID activity on different substrates remain to be identified. To better understand the latter issue, we tested how mutations in human AID (hAID) influence its ability to deaminate C, 5 mC, and 5 hmC in vitro...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623268/ascorbate-induces-apoptosis-in-melanoma-cells-by-suppressing-clusterin-expression
#3
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
#4
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/28601635/silencing-hif-1%C3%AE-induces-tet2-expression-and-augments-ascorbic-acid-induced-5-hydroxymethylation-of-dna-in-human-metastatic-melanoma-cells
#5
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...
August 19, 2017: Biochemical and Biophysical Research Communications
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
#6
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/28484589/idh1-or-2-mutations-do-not-predict-outcome-and-do-not-cause-loss-of-5-hydroxymethylcytosine-or-altered-histone-modifications-in-central-chondrosarcomas
#7
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
https://www.readbyqxmd.com/read/28448110/heavy-metals-induce-decline-of-derivatives-of-5-methycytosine-in-both-dna-and-rna-of-stem-cells
#8
Jun Xiong, Xiaona Liu, Qing-Yun Cheng, Shan Xiao, Lai-Xin Xia, Bi-Feng Yuan, Yu-Qi Feng
Toxic heavy metals have been considered to be harmful environmental contaminations. The molecular mechanisms of heavy-metals-induced cytotoxicity and carcinogenicity are still not well elucidated. Previous reports showed exposures to toxic heavy metals can cause a change of DNA cytosine methylation (5-methylcytosine, 5-mC). However, it is still not clear whether heavy metals have effects on the recently identified new epigenetic marks in both DNA and RNA, i.e., 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC)...
May 3, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28422379/increased-5-hydroxymethylation-levels-in-the-hippocampus-of-rat-extinguished-from-cocaine-self-administration
#9
Anna Sadakierska-Chudy, Małgorzata Frankowska, Karolina Wydra, Joanna Jastrzębska, Joanna Miszkiel, Małgorzata Filip
Drug craving and relapse risk during abstinence from cocaine are thought to be caused by persistent changes in transcription and chromatin regulation. Although several brain regions are involved in these processes, the hippocampus seems to play an important role in context-evoked craving and drug-seeking behavior. Only a few studies have examined epigenetic alterations during a period of cocaine abstinence. To investigate the effects of cocaine abstinence on DNA methylation and gene expression, rats that self-administered the drug underwent cocaine abstinence in two time points with extinction training...
July 2017: Hippocampus
https://www.readbyqxmd.com/read/28350187/epigenetic-status-of-h19-igf2-imprinted-genes-and-loss-of-5-hydroxymethylcytosine-in-the-brain-of-cloned-goats
#10
Mingtian Deng, Caifang Ren, Zifei Liu, Guomin Zhang, Feng Wang, Yongjie Wan
In mammals, the imprinted genes play vital roles in development and are generally controlled by DNA methylation at imprinting control regions (ICRs). Recently, it was discovered that 5-hydroxymethylcytosine (5-hmC) is a stable epigenetic modification; however, its functions in cloned animal genomes have not yet been fully elucidated. In this study, we interrogated and quantified the 5-hmC levels in the brain of cloned goats and discovered upregulation of Uhrf1 (p < 0.001), Dnmt1 (p < 0.05), Dnmt3a (p < 0...
June 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28349832/differential-expression-of-ten-eleven-translocation-genes-in-endometrial-cancers
#11
Piotr Ciesielski, Paweł Jóźwiak, Katarzyna Wójcik-Krowiranda, Ewa Forma, Łukasz Cwonda, Sylwia Szczepaniec, Andrzej Bieńkiewicz, Magdalena Bryś, Anna Krześlak
Ten-eleven translocation proteins are α-ketoglutarate-dependent dioxygenases involved in the conversion of 5-methylcytosines (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine, and 5-carboxylcytosine that play a significant role in DNA demethylation. Deregulation of TET genes expression and changes in the level of 5-hmC are thought to be associated with the onset and progression of several types of cancer, but there are no such data related to endometrial cancer. The aim of the work was to investigate the messenger RNA expression levels of TET1, TET2, and TET3 in relation to clinicopathological characteristics of endometrial cancer as well as the correlation between expression of TET genes and the level of 5-hmC/5-mC...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28293326/line-1-is-preferentially-hypomethylated-within-adenomatous-polyps-in-the-presence-of-synchronous-colorectal-cancer
#12
Alice Chu Jiang, Lela Buckingham, William Barbanera, Amoah Yeboah Korang, Faraz Bishesari, Joshua Melson
BACKGROUND: Conventional tubular adenomas are frequently detected in patients undergoing average risk screening colonoscopy and are over-represented in patients who will develop colorectal cancer (CRC). Whether features of adenomas could serve as predictors of synchronous CRC is not known. Here, we investigate whether global methylation markers, including LINE-1, differ within adenomas in patients with and without synchronous CRC. METHODS: Colorectal tubular/tubulovillous adenomatous polyps in the absence (P group, n = 45) and in the presence of synchronous CRC (PC group, n = 32) were identified...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28272491/ten-eleven-translocation-2-tet2-is-involved-in-myogenic-differentiation-of-skeletal-myoblast-cells-in-vitro
#13
Xia Zhong, Qian-Qian Wang, Jian-Wei Li, Yu-Mei Zhang, Xiao-Rong An, Jian Hou
Muscle cell differentiation is a complex process that is principally governed by related myogenic regulatory factors (MRFs). DNA methylation is considered to play an important role on the expression of MRF genes and on muscle cell differentiation. However, the roles of enzymes specifically in myogenesis are not fully understood. Here, we demonstrate that Tet2, a ten-eleven translocation (Tet) methylcytosine dioxygenase, exerts a role during skeletal myoblast differentiation. By using an immunostaining method, we found that the levels of 5-hydroxymethylcytosine (5-hmC) were much higher in differentiated myotubes than in undifferentiated C2C12 myoblasts...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28242787/tet2-in-normal-and-malignant-hematopoiesis
#14
Robert L Bowman, Ross L Levine
The ten-eleven translocation (TET) family of enzymes were originally cloned from the translocation breakpoint of t(10;11) in infant acute myeloid leukemia (AML) with subsequent genomic analyses revealing somatic mutations and suppressed expression of TET family members across a range of malignancies, particularly enriched in hematological neoplasms. The TET family of enzymes is responsible for the hydroxylation of 5-methylcytosines (5-mC) to 5-hydroxymethylcytosine (5-hmC), followed by active and passive mechanisms leading to DNA demethylation...
February 27, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28225433/the-role-of-5-hydroxymethylcytosine-in-melanoma
#15
Feng-Juan Li, Li-Ming Li, Rui-Hua Zhang, Cui Xu, Pan Zhou, Jia Long, Gang Hu, Ming-Jun Jiang
Malignant melanoma is a highly aggressive neoplasia of melanocytic origin. In part because of the lack of effective treatment methods, the incidence and mortality rates of this disease continue to increase. Rapidly accumulating evidence suggests that dysregulation of epigenetic mechanisms, including DNA methylation/demethylation, chromatin modification, and remodeling, and diverse activities of noncoding RNAs, play a central role in the pathogenesis of melanoma. The epigenetic mark 5-hydroxymethylcytosine (5-hmC) has attracted interest since 2009, when it was shown that ten-eleven translocation proteins can enzymatically convert 5-methylcytosine into 5-hmC, a key intermediate of DNA demethylation...
June 2017: Melanoma Research
https://www.readbyqxmd.com/read/28192296/simple-and-cost-effective-fluorescent-labeling-of-5-hydroxymethylcytosine
#16
Tamar Shahal, Ori Green, Uri Hananel, Yael Michaeli, Doron Shabat, Yuval Ebenstein
The nucleobase 5-hydroxymethylcytosine (5-hmC), a modified form of cytosine, is an important epigenetic mark related to regulation of gene expression. 5-hmC levels are highly dynamic during early development and are modulated during the progression of neurodegenerative disease and cancer. We describe a spectroscopic method for the global quantification of 5-hmC in genomic DNA. This method relies on the enzymatic glucosylation of 5-hmC, followed by a glucose oxidation step that results in the formation of aldehyde moieties that are covalently linked to a fluorescent reporter by oxime ligation...
October 7, 2016: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/28100914/tet-mediated-hydroxymethylcytosine-at-the-ppar%C3%AE-locus-is-required-for-initiation-of-adipogenic-differentiation
#17
Y Yoo, J H Park, C Weigel, D B Liesenfeld, D Weichenhan, C Plass, D-G Seo, A M Lindroth, Y J Park
BACKGROUND/OBJECTIVES: Adipose tissue is one of the main organs regulating energy homeostasis via energy storage as well as endocrine function. The adipocyte cell number is largely determined by adipogenesis. While the molecular mechanism of adipogenesis has been extensively studied, its role in dynamic DNA methylation plasticity remains unclear. Recently, it has been shown that Tet methylcytosine dioxygenase (TET) is catalytically capable of oxidizing DNA 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) toward a complete removal of the methylated cytosine...
April 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28040665/spectroscopic-quantification-of-5-hydroxymethylcytosine-in-genomic-dna-using-boric-acid-functionalized-nano-microsphere-fluorescent-probes
#18
Hua-Yan Chen, Jing-Ru Wei, Jiong-Xiu Pan, Wei Zhang, Fu-Quan Dang, Zhi-Qi Zhang, Jing Zhang
5-hydroxymethylcytosine (5hmC) is the sixth base of DNA. It is involved in active DNA demethylation and can be a marker of diseases such as cancer. In this study, we developed a simple and sensitive 2-(4-boronophenyl)quinoline-4-carboxylic acid modified poly (glycidyl methacrylate (PBAQA-PGMA) fluorescent probe to detect the 5hmC content of genomic DNA based on T4 β-glucosyltransferase-catalyzed glucosylation of 5hmC. The fluorescence-enhanced intensity recorded from the DNA sample was proportional to its 5-hydroxymethylcytosine content and could be quantified by fluorescence spectrophotometry...
May 15, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28032662/5-hydroxymethylcytosine-is-a-nuclear-biomarker-to-assess-biological-potential-in-histologically-ambiguous-heavily-pigmented-melanocytic-neoplasms
#19
Jonathan J Lee, Ricardo E Vilain, Scott R Granter, Nina R Hu, Scott C Bresler, Shuyun Xu, Alexander H Frank, Martin C Mihm, Robyn P M Saw, Christopher D Fletcher, Richard A Scolyer, George F Murphy, Christine G Lian
BACKGROUND: 5-Hydroxymethylcytosine (5-hmC) is an epigenetic marker detectable through immunohistochemistry (IHC) that has been shown to distinguish benign nevi from melanoma with high sensitivity and specificity. The purpose of the study was to explore its diagnostic utility in a subset of histologically challenging, heavily pigmented cutaneous melanocytic neoplasms. METHODS: 5-hmC IHC was performed on 54 heavily pigmented melanocytic tumors. Semi-quantitative analysis of immunoreactivity was correlated with clinical, pathologic and follow-up data...
December 29, 2016: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/27997431/attenuation-of-genome-wide-5-methylcytosine-level-is-an-epigenetic-feature-of-cutaneous-malignant-melanomas
#20
Goran Micevic, Nicholas Theodosakis, Janis M Taube, Marcus W Bosenberg, Nemanja Rodić
Epigenetic modification of DNA, namely covalent changes of cytosine residues, plays a key role in the maintenance of inactive chromatin regions, both in health and in disease. In the vast majority of malignant melanomas, the most notable known epigenetic abnormality is the attenuation of 5-hydroxymethylcytosine (5-hmC) residues. However, it remains unknown whether a decrease in 5-hmC represents a primary defect of melanoma cancer epigenome or whether it is secondary to the loss of 5-methylcytosine (5-mC), a chemical substrate for 5-hmC...
December 16, 2016: Melanoma Research
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