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5-hydroxymethylcytosine

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https://www.readbyqxmd.com/read/28107650/acetylation-enhances-tet2-function-in-protecting-against-abnormal-dna-methylation-during-oxidative-stress
#1
Yang W Zhang, Zhihong Wang, Wenbing Xie, Yi Cai, Limin Xia, Hariharan Easwaran, Jianjun Luo, Ray-Whay Chiu Yen, Yana Li, Stephen B Baylin
TET proteins, by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are hypothesized, but not directly shown, to protect promoter CpG islands (CGIs) against abnormal DNA methylation (DNAm) in cancer. We define such a protective role linked to DNA damage from oxidative stress (OS) known to induce this abnormality. TET2 removes aberrant DNAm during OS through interacting with DNA methyltransferases (DNMTs) in a "Yin-Yang" complex targeted to chromatin and enhanced by p300 mediated TET2 acetylation...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28100914/tet-mediated-hydroxymethylcytosine-at-the-ppar%C3%AE-locus-is-required-for-initiation-of-adipogenic-differentiation
#2
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) are catalytically capable of oxidizing DNA 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) towards a complete removal of the methylated cytosine...
January 19, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28100169/medium-throughput-bisulfite-sequencing-for-accurate-detection-of-5-methylcytosine-and-5-hydroxymethylcytosine
#3
Gary G Chen, Jeffrey A Gross, Pierre-Eric Lutz, Kathryn Vaillancourt, Gilles Maussion, Alexandre Bramoulle, Jean-François Théroux, Elena S Gardini, Ulrike Ehlert, Geneviève Bourret, Aurélie Masurel, Pierre Lepage, Naguib Mechawar, Gustavo Turecki, Carl Ernst
BACKGROUND: Epigenetic modifications of DNA, such as 5-methylcytosine and 5-hydroxymethycytosine, play important roles in development and disease. Here, we present a cost-effective and versatile methodology for the analysis of DNA methylation in targeted genomic regions, which comprises multiplexed, PCR-based preparation of bisulfite DNA libraries followed by customized MiSeq sequencing. RESULTS: Using bisulfite and oxidative bisulfite conversion of DNA, we have performed multiplexed targeted sequencing to analyse several kilobases of genomic DNA in up to 478 samples, and achieved high coverage data of 5-methylcytosine and 5-hydroxymethycytosine at single-base resolution...
January 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28089213/a-genome-wide-profiling-of-brain-dna-hydroxymethylation-in-alzheimer-s-disease
#4
Jinying Zhao, Yun Zhu, Jingyun Yang, Lin Li, Hao Wu, Philip L De Jager, Peng Jin, David A Bennett
INTRODUCTION: DNA methylation is a key epigenetic mechanism in brain aging and Alzheimer's disease (AD). The newly discovered 5-hydroxymethylcytosine mediates DNA demethylation, is highly abundant in the brain, and is dynamically regulated by life experiences. However, little is known about its genome-wide patterns and potential role in AD. METHODS: Using a genome-wide capture followed by high-throughput sequencing, we studied the genome-wide distribution of 5-hydroxymethylcytosine at specific genomic loci in human AD brain and identified differentially hydroxymethylated regions (DhMRs) associated with AD pathology...
January 6, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28052262/neil3-dependent-regulation-of-cardiac-fibroblast-proliferation-prevents-myocardial-rupture
#5
Maria B Olsen, Gunn A Hildrestrand, Katja Scheffler, Leif Erik Vinge, Katrine Alfsnes, Vuk Palibrk, Junbai Wang, Christine G Neurauter, Luisa Luna, Jostein Johansen, Jonas D S Øgaard, Ingrid K Ohm, Geir Slupphaug, Anna Kuśnierczyk, Arnt E Fiane, Sverre-Henning Brorson, Lili Zhang, Lars Gullestad, William E Louch, Per Ole Iversen, Ingunn Østlie, Arne Klungland, Geir Christensen, Ivar Sjaastad, Pål Sætrom, Arne Yndestad, Pål Aukrust, Magnar Bjørås, Alexandra V Finsen
Myocardial infarction (MI) triggers a reparative response involving fibroblast proliferation and differentiation driving extracellular matrix modulation necessary to form a stabilizing scar. Recently, it was shown that a genetic variant of the base excision repair enzyme NEIL3 was associated with increased risk of MI in humans. Here, we report elevated myocardial NEIL3 expression in heart failure patients and marked myocardial upregulation of Neil3 after MI in mice, especially in a fibroblast-enriched cell fraction...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28051309/chemical-modifications-to-rna-a-new-layer-of-gene-expression-regulation
#6
Jinghui Song, Chengqi Yi
The first chemical modification to RNA was discovered nearly 60 years ago; to date, more than 100 chemically distinct modifications have been identified in cellular RNA. With the recent development of novel chemical and/or biochemical methods, dynamic modifications to RNA have been identified in the transcriptome, including N(6)-methyladenosine (m(6)A), inosine (I), 5-methylcytosine (m(5)C), pseudouridine (Ψ), 5-hydroxymethylcytosine (hm(5)C), and N(1)-methyladenosine (m(1)A). Collectively, the multitude of RNA modifications are termed epitranscriptome, leading to the emerging field of epitranscriptomics...
January 12, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28043375/comparative-dynamics-of-5-methylcytosine-reprogramming-and-tet-family-expression-during-preimplantation-mammalian-development-in-mouse-and-sheep
#7
F Jafarpour, S M Hosseini, S Ostadhosseini, H Abbasi, A Dalman, M H Nasr-Esfahani
Despite previous assumption that paternal active DNA demethylation is an evolutionary conserved phenomenon in mammals, emerging studies in other species, particularly sheep, do not support this issue. Recently, ten eleven translocation (TET) enzymes have been suggested as intermediates in genome-wide DNA demethylation through the iterative conversion of five methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC)/5-formylcytosine/5-carboxylcytosine (5caC) derivatives. This study investigated whether TET enzymes and 5mC derivatives are also involved in dynamic reprogramming of early sheep embryos derived by fertilization...
February 2017: Theriogenology
https://www.readbyqxmd.com/read/28040665/spectroscopic-quantification-of-5-hydroxymethylcytosine-in-genomic-dna-using-boric-acid-functionalized-nano-microsphere-fluorescent-probes
#8
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...
December 16, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28039446/5-hydroxymethylcytosine-correlates-with-epigenetic-regulatory-mutations-but-may-not-have-prognostic-value-in-predicting-survival-in-normal-karyotype-acute-myeloid-leukemia
#9
Jae-Sook Ahn, Hyeoung-Joon Kim, Yeo-Kyeoung Kim, Seung-Shin Lee, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Hee Jeong Park, Seung Hyun Choi, Chul Won Jung, Jun-Ho Jang, Hee Je Kim, Joon Ho Moon, Sang Kyun Sohn, Jong-Ho Won, Sung-Hyun Kim, Szardenings Michael, Mark D Minden, Dennis Dong Hwan Kim
Stem cells display remarkably high levels of 5-hydroxymethylcytosine (5hmC). Both TET2 and IDH1/2 mutations can impair the production of 5hmC, thus decreasing 5hmC levels. TET2 or IDH1/2 mutations are commonly observed in acute myeloid leukemia (AML). However, the implications of 5hmC on survival in normal karyotype AML patients have not been fully evaluated. The 5hmC levels were analyzed in 375 patients using ELISA. The levels of 5hmC in DNA samples were converted to a log scale for the analysis and correlations with TET2 and/or IDH1/2 mutations were evaluated...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28038447/proteome-alterations-associated-with-transformation-of-multiple-myeloma-to-secondary-plasma-cell-leukemia
#10
Alexey Zatula, Aida Dikic, Celine Mulder, Animesh Sharma, Cathrine B Vågbø, Mirta M L Sousa, Anders Waage, Geir Slupphaug
Plasma cell leukemia is a rare and aggressive plasma cell neoplasm that may either originate de novo (primary PCL) or by leukemic transformation of multiple myeloma (MM) to secondary PCL (sPCL). The prognosis of sPCL is very poor, and currently no standard treatment is available due to lack of prospective clinical studies. In an attempt to elucidate factors contributing to transformation, we have performed super-SILAC quantitative proteome profiling of malignant plasma cells collected from the same patient at both the MM and sPCL stages of the disease...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032662/5-hydroxymethylcytosine-is-a-nuclear-biomarker-to-assess-biological-potential-in-histologically-ambiguous-heavily-pigmented-melanocytic-neoplasms
#11
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/28032215/a-driver-role-for-gaba-metabolism-in-controlling-stem-and-proliferative-cell-state-through-ghb-production-in-glioma
#12
Elias A El-Habr, Luiz G Dubois, Fanny Burel-Vandenbos, Alexandra Bogeas, Joanna Lipecka, Laurent Turchi, François-Xavier Lejeune, Paulo Lucas Cerqueira Coehlo, Tomohiro Yamaki, Bryan M Wittmann, Mohamed Fareh, Emna Mahfoudhi, Maxime Janin, Ashwin Narayanan, Ghislaine Morvan-Dubois, Charlotte Schmitt, Maité Verreault, Lisa Oliver, Ariane Sharif, Johan Pallud, Bertrand Devaux, Stéphanie Puget, Penelope Korkolopoulou, Pascale Varlet, Chris Ottolenghi, Isabelle Plo, Vivaldo Moura-Neto, Thierry Virolle, Hervé Chneiweiss, Marie-Pierre Junier
Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product GHB (4-hydroxybutyrate). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation...
December 28, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/28032024/urinary-measurement-of-epigenetic-dna-modifications-a-non-invasive-assessment-of-the-whole-body-epigenetic-status-in-healthy-subjects-and-colorectal-cancer-patients
#13
Rafal Rozalski, Daniel Gackowski, Agnieszka Siomek-Gorecka, Zbigniew Banaszkiewicz, Ryszard Olinski
Active mechanism of DNA demethylation can be responsible for the activation of previously silenced genes. Products of 5-methylcytosine oxidation are released into the bloodstream and eventually excreted with urine. Therefore, whole-body epigenetic status can be assessed non-invasively on the basis of the urinary excretion of a broad spectrum of epigenetic modifications: 5-hydroxymethylcytosine (5-hmCyt), 5-formylcytosine (5-fCyt), 5-carboxycytosine (5-caCyt), and 5-hydroxymethyluracil (5-hmUra). We have developed a specific and sensitive, isotope-dilution, automated, online, two-dimensional ultra-performance liquid chromatography system with tandem mass spectrometry (2D UPLC-MS/MS) to measure 5-hmCyt, 5-fCyt, 5-caCyt, and their deoxynucleosides in the same urine sample...
December 2016: ChemistryOpen
https://www.readbyqxmd.com/read/28030787/dna-demethylation-mediated-by-down-regulated-tets-in-the-testes-of%C3%A2-rare-minnow-gobiocypris-rarus-under-bisphenol-a-exposure
#14
Cong Yuan, Yingying Zhang, Yan Liu, Song Wang, Zaizhao Wang
Inevitable BPA exposure resulted in disturbance of DNA methylation status and our published study suspected that BPA has the potentiality to disturb DNA demethylation and GSH production in Gobiocypris rarus testes. To confirm this conjecture, several experiments were carried out in the present study. Adult male G. rarus was exposed to 1, 15 and 225 μg L(-1) (nominal concentration) BPA for two weeks. The levels of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), glutathione (GSH), and enzyme levels for DNA methylation and GSH synthesis in the testes were detected...
December 21, 2016: Chemosphere
https://www.readbyqxmd.com/read/28003489/restricted-tet2-expression-in-germinal-center-type-b-cells-promotes-stringent-epstein-barr-virus-latency
#15
Coral K Wille, Yangguang Li, Lixin Rui, Eric C Johannsen, Shannon C Kenney
: EBV latently infects normal B cells, and contributes to the development of certain human lymphomas. Newly infected B cells support a highly transforming form (type III) of viral latency; however, long-term EBV infection in immunocompetent hosts is limited to B cells with a more restricted form of latency (type I) where most viral gene expression is silenced by promoter DNA methylation. How EBV converts latency type is unclear, although it is known that type I latency is associated with germinal center (GC) B cell phenotype, and type III latency with an activated B-cell (ABC) phenotype...
December 21, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27997431/attenuation-of-genome-wide-5-methylcytosine-level-is-an-epigenetic-feature-of-cutaneous-malignant-melanomas
#16
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
https://www.readbyqxmd.com/read/27981856/distinct-cellular-and-molecular-environments-support-aging-related-dna-methylation-changes-in-the-substantia-nigra
#17
Maria Fasolino, Shuo Liu, Yinsheng Wang, Zhaolan Zhou
AIM: We aimed to couple brain region-specific changes in global DNA methylation over aging to underlying cellular and molecular environments. MATERIALS & METHODS: We measured two major forms of DNA methylation and analyzed Dnmt, Tet and metabolite levels in the striatum and substantia nigra (SN) over aging in healthy male mice. RESULTS: The ratio of 5-hydroxymethylcytosine to 5-methylcytosine increases over aging in the SN, and 5-hydroxymethylcytosine increases preferentially in dopaminergic neurons...
January 2017: Epigenomics
https://www.readbyqxmd.com/read/27951657/5-methylcytosine-5mc-and-5-hydroxymethylcytosine-5hmc-enhance-the-dna-binding-of-creb1-to-the-c-ebp-half-site-tetranucleotide-gcaa
#18
Khund Sayeed Syed, Ximiao He, Desiree Tillo, Jun Wang, Stewart R Durell, Charles Vinson
In human and mouse stem cells and brain, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) can occur outside of CG dinucleotides. Using protein binding microarrays (PBMs) containing 60-mer DNA probes, we evaluated the effect of 5mC and 5hmC on one DNA strand on the double-stranded DNA binding of the mouse B-ZIP transcription factors (TFs) CREB1, ATF1, and JUND. 5mC inhibited binding of CREB1 to the canonical CRE half-site |GTCA but enhanced binding to the C/EBP half-site |GCAA. 5hmC inhibited binding of CREB1 to all 8-mers except TGAT|GCAA, where binding is enhanced...
December 13, 2016: Biochemistry
https://www.readbyqxmd.com/read/27936926/the-application-of-genome-wide-5-hydroxymethylcytosine-studies-in-cancer-research
#19
John P Thomson, Richard R Meehan
Early detection and characterization of molecular events associated with tumorgenesis remain high priorities. Genome-wide epigenetic assays are promising diagnostic tools, as aberrant epigenetic events are frequent and often cancer specific. The deposition and analysis of multiple patient-derived cancer epigenomic profiles contributes to our appreciation of the underlying biology; aiding the detection of novel identifiers for cancer subtypes. Modifying enzymes and co-factors regulating these epigenetic marks are frequently mutated in cancers, and as epigenetic modifications themselves are reversible, this makes their study very attractive with respect to pharmaceutical intervention...
January 2017: Epigenomics
https://www.readbyqxmd.com/read/27930333/tet-proteins-influence-the-balance-between-neuroectodermal-and-mesodermal-fate-choice-by-inhibiting-wnt-signaling
#20
Xiang Li, Xiaojing Yue, William A Pastor, Lizhu Lin, Romain Georges, Lukas Chavez, Sylvia M Evans, Anjana Rao
TET-family dioxygenases catalyze conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and oxidized methylcytosines in DNA. Here, we show that mouse embryonic stem cells (mESCs), either lacking Tet3 alone or with triple deficiency of Tet1/2/3, displayed impaired adoption of neural cell fate and concomitantly skewed toward cardiac mesodermal fate. Conversely, ectopic expression of Tet3 enhanced neural differentiation and limited cardiac mesoderm specification. Genome-wide analyses showed that Tet3 mediates cell-fate decisions by inhibiting Wnt signaling, partly through promoter demethylation and transcriptional activation of the Wnt inhibitor secreted frizzled-related protein 4 (Sfrp4)...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
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