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5 hydroxymethylcytosine

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https://www.readbyqxmd.com/read/28211484/regulation-of-mrna-splicing-by-mecp2-via-epigenetic-modifications-in-the-brain
#1
Tian-Lin Cheng, Jingqi Chen, Huida Wan, Bin Tang, Weidong Tian, Lujian Liao, Zilong Qiu
Mutations of X-linked gene Methyl CpG binding protein 2 (MECP2) are the major causes of Rett syndrome (RTT), a severe neurodevelopmental disorder. Duplications of MECP2-containing genomic segments lead to severe autistic symptoms in human. MECP2-coding protein methyl-CpG-binding protein 2 (MeCP2) is involved in transcription regulation, microRNA processing and mRNA splicing. However, molecular mechanisms underlying the involvement of MeCP2 in mRNA splicing in neurons remain largely elusive. In this work we found that the majority of MeCP2-associated proteins are involved in mRNA splicing using mass spectrometry analysis with multiple samples from Mecp2-null rat brain, mouse primary neuron and human cell lines...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193047/accurate-direct-and-high-throughput-analyses-of-a-broad-spectrum-of-endogenously-generated-dna-base-modifications-with-isotope-dilution-two-dimensional-ultraperformance-liquid-chromatography-with-tandem-mass-spectrometry-possible-clinical-implication
#2
Daniel Gackowski, Marta Starczak, Ewelina Zarakowska, Martyna Modrzejewska, Anna Szpila, Zbigniew Banaszkiewicz, Ryszard Olinski
Our hereby presented methodology is suitable for reliable assessment of the most common unavoidable DNA modifications which arise as a product of fundamental metabolic processes. 8-Oxoguanine, one of the oxidatively modified DNA bases, is a typical biomarker of oxidative stress. A noncanonical base, uracil, may be also present in small quantities in DNA. A set of ten-eleven translocation (TET) proteins are involved in oxidation of 5-methylcytosine to 5-hydroxymethylcytosine which can be further oxidized to 5-formylcytosine and 5-carboxycytosine...
December 20, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/28192296/simple-and-cost-effective-fluorescent-labeling-of-5-hydroxymethylcytosine
#3
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/28192139/vitamin-c-down-regulate-apo-a-expression-via-tet2-dependent-dna-demethylation-in-hepg2-cells
#4
Kai Qu, Xiao-Feng Ma, Guo-Hua Li, Hai Zhang, Ya-Mi Liu, Kai Zhang, Jun-Fa Zeng, Jian-Jun Lei, Dang-Heng Wei, Zuo Wang
Lipoprotein(a)[Lp(a)] is a risk factor for coronary heart diseases. However, the metabolism of this protein remains poorly understood. Efficient and specific drugs that can decrease high plasma levels of Lp(a) have not been developed yet. Vitamin C is responsible for maintaining the catalytic activity of a group of iron and 2-oxoglutarate (2OG)-dependent dioxygenases and induces the generation of 5-hydroxymethylcytosine (5hmC) via Ten-eleven translocation (Tet) dioxygenases. In addition, It has been reported vitamin C deficiency induces atherosclerosis and increases Lp(a) and apo(a) plasma levels in Lp(a)+ mice...
February 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28141796/epigenomic-landscape-of-5-hydroxymethylcytosine-reveals-its-transcriptional-regulation-of-lncrnas-in-colorectal-cancer
#5
Hanyang Hu, Maoguo Shu, Lin He, Xueyuan Yu, Xiangyu Liu, Yalin Lu, Yinghong Chen, Xiaoping Miao, Xiaohua Chen
BACKGROUND: DNA methylation at the 5 position of cytosine (5mC) can be converted to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation family. The loss of global levels of 5hmC has been regarded as a hallmark in various cancers. 5-hydroxymethylcytosine is distributed at protein-coding gene bodies and promoters; however, the role and distribution of 5hmC at long non-coding RNAs (lncRNAs) is not clear. We investigated the distribution and regulatory roles of 5hmC for lncRNAs in colorectal cancer (CRC)...
January 31, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28130236/h-o-ta-estimation-of-dna-methylation-and-hydroxylation-levels-and-efficiencies-from-time-course-data
#6
Charalampos Kyriakopoulos, Pascal Giehr, Verena Wolf
MOTIVATION: Methylation and hydroxylation of cytosines to form 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) belong to the most important epigenetic modifications and their vital role in the regulation of gene expression has been widely recognized. Recent experimental techniques allow to infer methylation and hydroxylation levels at CpG dinucleotides but require a sophisticated statistical analysis to achieve accurate estimates. RESULTS: We present H(O)TA, a software tool based on a stochastic modeling approach, which simultaneously analyzes time course data from hairpin bisulfite sequencing and hairpin oxidative bisulfite sequencing...
January 27, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28128679/early-life-stress-links-5-hydroxymethylcytosine-to-anxiety-related-behaviors
#7
Ligia A Papale, Andy Madrid, Sisi Li, Reid S Alisch
Environmental stress contributes to the development of psychiatric disorders, including post-traumatic stress disorder and anxiety. While even acute stress alters gene expression, the molecular mechanisms underlying these changes remain largely unknown. 5-hydroxymethylcytosine (5hmC) is a novel environmentally sensitive DNA modification that is highly enriched in the brain and is associated with active transcription of neuronal genes. Here we examined behavioral and molecular alterations in adult mice that experienced an early-life stress prior to weaning (postnatal day 12 to 18) and found anxiety-like behaviors in adult female mice that were accompanied by correlated disruptions of hypothalamic 5hmC and gene expression in 118 genes, revealing potentially functional 5hmC (i...
January 27, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28125731/correlated-5-hydroxymethylcytosine-5hmc-and-gene-expression-profiles-underpin-gene-and-organ-specific-epigenetic-regulation-in-adult-mouse-brain-and-liver
#8
I-Hsuan Lin, Yi-Fan Chen, Ming-Ta Hsu
BACKGROUND: DNA methylation is an epigenetic mechanism essential for gene regulation and vital for mammalian development. 5-hydroxymethylcytosine (5hmC) is the first oxidative product of the TET-mediated 5-methylcytosine (5mC) demethylation pathway. Aside from being a key intermediate in cytosine demethylation, 5hmC may have potential regulatory functions with emerging importance in mammalian biology. METHODS: Here, we investigate the global 5hmC enrichment in five brain structures, including cerebellum, cerebral cortex, hippocampus, hypothalamus and thalamus, as well as liver tissues from female and male adult mice by using chemical capture-based technique coupled with next-generation sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/28115643/zno-nanoparticles-induced-reactive-oxygen-species-promotes-multimodal-cyto-and-epigenetic-toxicity
#9
Samrat Roy Choudhury, Josue Ordaz, Chiao-Ling Lo, Nur P Damayanti, Feng Zhou, Joseph Irudayaraj
In this study we evaluated and correlated the cytotoxic effects of zinc oxide nanoparticles (ZnO-NPs) to epigenetic modifications, using human embryonic kidney (HEK-293) cells as a model system. Imaging of singlet and total reactive oxygen species (ROS) in ZnO-NPs treated live cells was performed followed by the evaluation of its effects on cytoskeletal, mitochondrial, and nuclear integrity, and on the expression of ROS responsive genes. Next, we determined the global and locus specific changes in DNA-methylation at the three genomic repeat sequences namely global LINE-1, subtelomeric D4Z4 and pericentromeric NBL2, and at the promoter of selected ROS responsive genes (AOX1, HMOX1, NCF2, SOD3)...
January 22, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28115522/the-5-hydroxymethylcytosine-5hmc-reader-uhrf2-is-required-for-normal-levels-of-5hmc-in-mouse-adult-brain-and-spatial-learning-and-memory
#10
Ruoyu Chen, Qiao Zhang, Xiaoya Duan, Philippe York, Guo-Dong Chen, Pengcheng Yin, Haijun Zhu, Meichen Xu, Peilin Chen, Qihan Wu, Dali Li, Jacques Samarut, Guoliang Xu, Pumin Zhang, Xiaohua Cao, Jiwen Li, Jiemin Wong
UHRF2 has been implicated as a novel regulator for both DNA methylation (5mC) and hydroxymethylation (5hmC), but its physiological function and role in DNA methylation/hydroxymethylation are unknown. Here we show that in mice Uhrf2 is more abundantly expressed in the brain and a few other tissues. Uhrf2 knockout mice are viable, fertile and exhibit no gross defect. Although there is no significant change of DNA methylation, the Uhrf2 null mice exhibit a reduction of 5hmC in the brain including cortex and hippocampus...
January 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28115210/the-methylation-of-nuclear-and-mitochondrial-dna-in-ageing-phenotypes-and-longevity
#11
REVIEW
Maria Giulia Bacalini, Patrizia D'Aquila, Elena Marasco, Christine Nardini, Alberto Montesanto, Claudio Franceschi, Giuseppe Passarino, Paolo Garagnani, Dina Bellizzi
An increasing body of data is progressively indicating that the comprehension of the epigenetic landscape, actively integrated with the genetic elements, is crucial to delineate the molecular basis of the inter-individual complexity of ageing process. Indeed, it has emerged that DNA methylation changes occur during ageing, consisting mainly in a progressive process of genome demethylation, in a hypermethylation of gene-specific CpG dinucleotides, as well as in an inter-individual divergence of the epigenome due to stochastic events and environmental exposures throughout life, namely as epigenetic drift...
January 20, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28115151/tetrachloro-1-4-benzoquinone-induces-apoptosis-of-mouse-embryonic-stem-cells
#12
Cuiping Li, Fengbang Wang, Hailin Wang
Pentachlorophenol (PCP) is a widespread, persistent environmental contaminant, and it is enzymatically activated to form a reactive metabolite, tetrachloro-1,4-benzoquinone (TCBQ). To our knowledge, there is no information about TCBQ toxicity on embryonic stem cells. Here, we demonstrated that TCBQ induced significantly apoptosis of mouse embryonic stem cells in a concentration-dependent manner. We also showed that TCBQ elevated genomic 5-hydroxymethylcytosine (5hmC) by affecting ten-eleven translocation (Tet) dioxygenases in mouse embryonic stem cells...
January 2017: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/28107650/acetylation-enhances-tet2-function-in-protecting-against-abnormal-dna-methylation-during-oxidative-stress
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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