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https://www.readbyqxmd.com/read/27903986/adult-t-cell-leukemia-aggressivenness-correlates-with-loss-of-both-5-hydroxymethylcytosine-and-tet2-expression
#1
Ambroise Marçais, Laetitia Waast, Julie Bruneau, Katia Hanssens, Vahid Asnafi, Philippe Gaulard, Felipe Suarez, Patrice Dubreuil, Antoine Gessain, Olivier Hermine, Claudine Pique
Mutations in TET2, encoding one of the TET members responsible for the conversion of DNA cytosine methylation to hydroxymethylation (5-hmc), have been recently described in Human T-lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma (ATLL). However, neither the amount of genomic 5-hmc in ATLL tumor cells nor TET2 expression has been studied yet. In this study, we analyzed these two parameters as well as the mutational status of TET2 in ATLL patients. By employing a direct in situ approach, we documented that tumor T cells infiltrating lymph nodes exhibit low level of 5-hmc compared to residual normal T cells...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889911/multiregional-analysis-of-global-5-methylcytosine-and-5-hydroxymethylcytosine-throughout-the-progression-of-alzheimer-s-disease
#2
Elizabeth M Ellison, Erin L Abner, Mark A Lovell
Epigenetic modifications to cytosine are known to alter transcriptional states and deregulate gene expression in cancer, embryonic development, and most recently in neurodegeneration. To test the hypothesis that global levels of cytosine modification are altered throughout the progression of Alzheimer's disease, 5-methylcytosine (5-mC) and 5-hydroxmethylcytosine (5-hmC) were quantified using gas chromatography/mass spectrometry (GC/MS) and stable labeled internal standards of cytosine, 5-mC, and 5-hmC. Cytosine modifications were quantified in DNA extracted from tissue specimens of four brain regions (cerebellum, inferior parietal lobe, superior and middle temporal gyrus, and hippocampus/parahippocampal gyrus) of cognitively normal control (NC) subjects and subjects with mild cognitive impairment (MCI), preclinical Alzheimer's disease (PCAD), late onset Alzheimer's disease (LOAD), frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies (DLB)...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27857218/tet1-dependent-epigenetic-modification-of-bdnf-expression-in-dorsal-horn-neurons-mediates-neuropathic-pain-in-rats
#3
Ming-Chun Hsieh, Cheng-Yuan Lai, Yu-Cheng Ho, Hsueh-Hsiao Wang, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
Ten-eleven translocation methylcytosine dioxygenase 1 (Tet1) mediates the conversion of 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC), hence promoting DNA demethylation. Although recent studies have linked the DNA demethylation of specific genes to pain hypersensitivity, the role of spinal Tet1-dependent DNA demethylation in nociception hypersensitivity development remains elusive. Here, we report correlated with behavioral allodynia, spinal nerve ligation (SNL) upregulated Tet1 expression in dorsal horn neurons that hydroxylate 5 mC to 5 hmC at CpG dinucleotides in the bdnf promoter to promote spinal BDNF expression at day 7 after operation...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27852070/epigenetic-silencing-of-tet2-and-tet3-induces-an-emt-like-process-in-melanoma
#4
Fuxing Gong, Yu Guo, Yiqian Niu, Jiawei Jin, Xiaojuan Zhang, Xiaoqian Shi, Limeng Zhang, Runting Li, Longxin Chen, Runlin Z Ma
Epithelial-Mesenchymal Transition (EMT) is a critical step in the progression of cancer. Malignant melanoma, a cancer developed from pigmented melanocytes, metastasizes through an EMT-like process. Ten-eleven translocation (TET) enzymes, catalyzing the conversion of 5-methylcytosine (5mC) to 5-hydroxylmethylcytosine (5-hmC), are down regulated in melanoma. However, their roles in the progression and the EMT-like process of melanoma are not fully understood. Here we report that DNA methylation induced silencing of TET2 and TET3 are responsible for the EMT-like process and the metastasis of melanoma...
November 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27848178/dysregulation-of-tet2-in-hematologic-malignancies
#5
REVIEW
Shigeru Chiba
The TET dioxygenases, TET1, TET2, and TET3, catalyze transfer of an oxygen atom to the methyl group of 5-methylcytocine (5-mC), converting it to 5-hydroxymethylcytocine (5-hmC). Among the genes encoding these enzymes, ten-eleven translocation 2 (TET2) is frequently mutated somatically in both myeloid and lymphoid malignancies. Because these TET2 mutations result in the impairment of the dioxygenase activity of TET2, it is thought that these mutations interfere with 5-mC to 5-hmC conversion. There is ample evidence indicating that TET2 mutations are a driver of tumorigenesis in blood cells and that TET2 mutations are often acquired at the hematopoietic stem/early progenitor cell stage...
November 15, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27825882/a-reusable-laser-wrapped-graphene-ag-array-based-sers-sensor-for-trace-detection-of-genomic-dna-methylation
#6
Lei Ouyang, Yaowu Hu, Lihua Zhu, Gary J Cheng, Joseph Irudayaraj
Methylation is an important epigenetic DNA modification that governs gene expression. The genomic level of methylated DNA and its derivatives may serve as important indicators for the initiation and progression of cancers among other diseases. In this effort we propose a new laser wrapped graphene-Ag array as a highly sensitive Surface-enhanced Raman spectroscopy (SERS) sensor for the detection of methylated DNA (5-methylcytosine, 5mC) and its oxidation derivatives namely 5-hydroxymethylcytosine (5-hmC) and 5-carboxylcytosine (5-caC)...
September 22, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27825418/research-advances-in-the-mutation-of-tet2-gene-in-myeloid-maligancies
#7
Rong Li, Ming-Jiang Xu, Feng-Chun Yang, Yuan Zhou
TET2 gene is a member of TET oncogene family. It has been reported as a tumor suppressor gene with important roles in myelopiesis. Recent studies have shown that TET2 protein takes part in demethylation by converting 5-methylcytosine (5-mc) into 5-hydroxymethylcytosine (5-hmc). Somatic TET2 inactivation leads to abnormal myelopiesis and myeloid malignancies. In this review,the structure and function of TET2 and the relationship between TET gene mutation and myeloid malignancies are summarized.
October 10, 2016: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/27803663/environmental-enrichment-modified-epigenetic-mechanisms-in-samp8-mouse-hippocampus-by-reducing-oxidative-stress-and-inflammaging-and-achieving-neuroprotection
#8
Christian Griñan-Ferré, Dolors Puigoriol-Illamola, Verónica Palomera-Ávalos, David Pérez-Cáceres, Júlia Companys-Alemany, Antonio Camins, Daniel Ortuño-Sahagún, M Teresa Rodrigo, Mercè Pallàs
With the increase in life expectancy, aging and age-related cognitive impairments are becoming one of the most important issues for human health. At the same time, it has been shown that epigenetic mechanisms are emerging as universally important factors in life expectancy. The Senescence Accelerated Mouse P8 (SAMP8) strain exhibits age-related deterioration evidenced in learning and memory abilities and is a useful model of neurodegenerative disease. In SAMP8, Environmental Enrichment (EE) increased DNA-methylation levels (5-mC) and reduced hydroxymethylation levels (5-hmC), as well as increased histone H3 and H4 acetylation levels...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27770360/analysis-of-dna-hydroxymethylation-using-colorimetric-assay
#9
Andrey Golubov, Igor Kovalchuk
Hydroxymethylcytosine (hmC or 5-hmC) is a nitrogen base occurring as a result of cytosine methylation followed by replacing a methyl group with a hydroxyl group through active oxidation. 5-hmC is considered to be one of the forms of epigenetic modification and is suggested as an intermediate step in a semi-active loss of DNA methylation mark. 5-hmC plays an important role in the epigenetic regulation of gene expression in animals, although its role in plants remains controversial. Here, we present a colorimetric method of quantification of 5-hmC using Brassica rapa DNA...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27713424/5-hydroxymethylcytosine-is-an-independent-predictor-of-survival-in-malignant-melanoma
#10
Gerald Saldanha, Kushal Joshi, Kathryn Lawes, Mark Bamford, Farhaan Moosa, Kah Wee Teo, J Howard Pringle
Outcomes for melanoma patients vary within cancer stage. Prognostic biomarkers are potential adjuncts to provide more precise prognostic information. Simple, low-cost biomarker assays, such as those based on immunohistochemistry, have strong translational potential. 5-hydroxymethylcytosine (5 hmC) shows prognostic potential in melanoma but prior studies were small. We, therefore, analysed 5 hmC in a retrospective cohort to provide external validation of its prognostic value. Two hundred primary melanomas were evaluated for 5 hmC expression using immunohistochemistry...
October 7, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27620533/discrimination-between-5-hydroxymethylcytosine-and-5-methylcytosine-in-dna-via-selective-electrogenerated-chemiluminescence-ecl-labeling
#11
Shangxian Ma, Huiping Sun, Yan Li, Honglan Qi, Jianbin Zheng
DNA methylation is used to dynamically reprogram cells in the course of early embryonic development in mammals. 5-Hydroxymethylcytosine in DNA (5-hmC-DNA) plays essential roles in the demethylation processes. 5-Methylcytosine in DNA (5-mC-DNA) is oxidized to 5-hmC-DNA by 10-11 translocation proteins, which are relatively high abundance in embryonic stem cells and neurons. A new method was developed herein to quantify 5-hmC-DNA based on selective electrogenerated chemiluminescence (ECL) labeling with the specific oxidation of 5-hmC to 5-fC by KRuO4...
October 18, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27494059/maternal-calorie-restriction-causing-uteroplacental-insufficiency-differentially-affects-mammalian-placental-glucose-and-leucine-transport-molecular-mechanisms
#12
Amit Ganguly, Marlin Touma, Shanthie Thamotharan, Darryl C De Vivo, Sherin U Devaskar
We examined the effect of mild (Mi; ∼25%) and moderate (Mo; ∼50%) maternal calorie restriction (MCR) vs ad libitum-fed controls on placental glucose and leucine transport impacting fetal growth potential. We observed in MiMCR a compensatory increase in transplacental (TP) glucose transport due to increased placental glucose transporter isoform (GLUT)-3 but no change in GLUT1 protein concentrations. This change was paralleled by increased glut3 mRNA and 5-hydroxymethylated cytosines with enhanced recruitment of histone 3 lysine demethylase to the glut3 gene locus...
October 2016: Endocrinology
https://www.readbyqxmd.com/read/27489048/dna-hydroxymethylation-controls-cardiomyocyte-gene-expression-in-development-and-hypertrophy
#13
Carolina M Greco, Paolo Kunderfranco, Marcello Rubino, Veronica Larcher, Pierluigi Carullo, Achille Anselmo, Kerstin Kurz, Thomas Carell, Andrea Angius, Michael V G Latronico, Roberto Papait, Gianluigi Condorelli
Methylation at 5-cytosine (5-mC) is a fundamental epigenetic DNA modification associated recently with cardiac disease. In contrast, the role of 5-hydroxymethylcytosine (5-hmC)-5-mC's oxidation product-in cardiac biology and disease is unknown. Here we assess the hydroxymethylome in embryonic, neonatal, adult and hypertrophic mouse cardiomyocytes, showing that dynamic modulation of hydroxymethylated DNA is associated with specific transcriptional networks during heart development and failure. DNA hydroxymethylation marks the body of highly expressed genes as well as distal regulatory regions with enhanced activity...
August 4, 2016: Nature Communications
https://www.readbyqxmd.com/read/27456754/5-hydroxymethylcytosine-expression-in-proliferative-nodules-arising-within-congenital-nevi-allows-differentiation-from-malignant-melanoma
#14
Olesya Pavlova, Sylvie Fraitag, Daniel Hohl
Differentiation of proliferative nodules in giant congenital nevi from melanoma arising within such nevi is an important diagnostic challenge. DNA methylation is a well-established epigenetic modification already observed in the earliest stages of carcinogenesis, which increases during melanoma progression. The ten-eleven translocation enzymes catalyze the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC), which has recently been reported as an epigenetic hallmark associated with tumor aggressiveness and poor prognosis in a wide variety of cancers...
July 22, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27383905/quantifying-mammalian-genomic-dna-hydroxymethylcytosine-content-using-solid-state-nanopores
#15
Osama K Zahid, Boxuan Simen Zhao, Chuan He, Adam R Hall
5-hydroxymethylcytosine (5 hmC), the oxidized form of 5-methylcytosine (5 mC), is a base modification with emerging importance in biology and disease. However, like most epigenetic elements, it is transparent to many conventional genetic techniques and is thus challenging to probe. Here, we report a rapid solid-state nanopore assay that is capable of resolving 5 hmC with high specificity and sensitivity and demonstrate its utility in assessing global modification abundance in genomic DNA.
2016: Scientific Reports
https://www.readbyqxmd.com/read/27356740/crispr-dcas9-mediated-tet1-targeting-for-selective-dna-demethylation-at-brca1-promoter
#16
Samrat Roy Choudhury, Yi Cui, Katarzyna Lubecka, Barbara Stefanska, Joseph Irudayaraj
DNA hypermethylation at the promoter of tumour-suppressor genes is tightly correlated with their transcriptional repression and recognized as the hallmark of majority of cancers. Epigenetic silencing of tumour suppressor genes impairs their cellular functions and activates a cascade of events driving cell transformation and cancer progression. Here, we examine site-specific and spatiotemporal alteration in DNA methylation at a target region in BRCA1 gene promoter, a model tumour suppressor gene. We have developed a programmable CRISPR-Cas9 based demethylase tool containing the deactivated Cas9 (dCas9) fused to the catalytic domain (CD) of Ten-Eleven Translocation (TET) dioxygenase1 (TET1CD)...
June 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27356236/high-throughput-sequencing-offers-new-insights-into-5-hydroxymethylcytosine
#17
Alina P S Pang, Christopher Sugai, Alika K Maunakea
Chemical modifications of DNA comprise epigenetic mechanisms that contribute to the maintenance of cellular activities and memory. Although the function of 5-methylcytosine (5-mC) has been extensively studied, little is known about the function(s) of relatively rarer and underappreciated cytosine modifications including 5-hydroxymethylcytosine (5-hmC). The discovery that ten-eleven translocation (Tet) proteins mediate conversion of 5-mC to 5-hmC, and other oxidation derivatives, sparked renewed interest to understand the biological role of 5-hmC...
June 1, 2016: Biomolecular Concepts
https://www.readbyqxmd.com/read/27313688/low-level-of-5-hydroxymethylcytosine-predicts-poor-prognosis-in-non-small-cell-lung-cancer
#18
Yunfei Liao, Jie Gu, Yongbing Wu, Xiang Long, D I Ge, Jianjun Xu, Jianyong Ding
The loss of 5-hydroxymethylcytosine (5-hmC) has previously been demonstrated to be implicated in the initiation and progression of various tumors. However, its role in non-small cell lung cancer (NSCLC) remains unknown. The present study aimed to determine the level of 5-hmC in NSCLC and their adjacent normal lung tissues by immunohistochemistry and dot-blot analysis; then the relationship between 5-hmC level and the clinicopathological features of NSCLC and the prognostic significance of 5-hmC level in NSCLC patients were analyzed...
June 2016: Oncology Letters
https://www.readbyqxmd.com/read/27294001/decreased-5-hydroxymethylcytosine-5-hmc-predicts-poor-prognosis-in-early-stage-laryngeal-squamous-cell-carcinoma
#19
Yanfang Zhang, Kexia Wu, Yuan Shao, Fang Sui, Qi Yang, Bingyin Shi, Peng Hou, Meiju Ji
Accumulating evidences suggest that large-scale loss of 5-hydroxymethylcytosine (5-hmC) is an epigenetic hallmark in different cancers. However, the levels of 5-hmC in laryngeal squamous cell carcinoma (LSCC) and its prognostic value in this cancer remain largely unknown. Using dot-blot and quantitative RT-PCR assays, we investigate 5-hmC levels and expression of TET-1, -2 and -3 in LSCCs and explore the association of 5-hmC levels with clinicopathological characteristics and clinical outcome of LSCC patients...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27289557/tet2-mediated-5-hydroxymethylcytosine-induces-genetic-instability-and-mutagenesis
#20
Emna Mahfoudhi, Ibtissam Talhaoui, Xenia Cabagnols, Véronique Della Valle, Lise Secardin, Philippe Rameau, Olivier A Bernard, Alexander A Ishchenko, Salem Abbes, William Vainchenker, Murat Saparbaev, Isabelle Plo
The family of Ten-Eleven Translocation (TET) proteins is implicated in the process of active DNA demethylation and thus in epigenetic regulation. TET 1, 2 and 3 proteins are oxygenases that can hydroxylate 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC) and further oxidize 5-hmC into 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). The base excision repair (BER) pathway removes the resulting 5-fC and 5-caC bases paired with a guanine and replaces them with regular cytosine. The question arises whether active modification of 5-mC residues and their subsequent elimination could affect the genomic DNA stability...
July 2016: DNA Repair
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