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5 hydroxymethylcytosine

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https://www.readbyqxmd.com/read/29432895/a-cross-omics-approach-to-investigate-temporal-gene-expression-regulation-by-5-hydroxymethylcytosine-via-tbh-derived-oxidative-stress-showed-involvement-of-different-regulatory-kinases
#1
Jacob J Briedé, Lize Deferme, Jarno E J Wolters, Sandra M H Claessen, Twan van den Beucken, J Richard Wagner, Simone G van Breda, Jos C S Kleinjans
Regulation of DNA methylation plays a crucial role in biological processes and carcinogenesis. The formation of 5-hydroxymethylcytosine (5hmC) by oxidation of 5-methylcytosine (5mC) has been proposed as an intermediate of active demethylation. However, whether and how active demethylation is regulated by oxidative stress-related processes is not well understood. Here we investigated whether free oxygen radicals are capable of directly forming 5hmC and how this enhanced whole genome gene expression. We applied LC-MS/MS technology for the analysis of 5mC, 5hmC, 5-formylcytosine (5fC) and 5-hydroxymethyluracyl (5hmU) in HepG2 cells exposed to hydroxyl- and methyl radicals, formed by tert-butyl hydroperoxide (TBH) at multiple time points...
February 9, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29428975/5-hydroxymethylcytosine-preferentially-targets-genes-upregulated-in-isocitrate-dehydrogenase-1-mutant-high-grade-glioma
#2
Wioletta K Glowacka, Harshika Jain, Makiko Okura, Abulizi Maimaitiming, Yasin Mamatjan, Romina Nejad, Hamza Farooq, Michael D Taylor, Kenneth Aldape, Paul Kongkham
Gliomas demonstrate epigenetic dysregulation exemplified by the Glioma CpG Island Methylator Phenotype (G-CIMP) seen in IDH1 mutant tumors. 5-Hydroxymethylcytosine (5hmC) is implicated in glioma pathogenesis; however, its role in IDH1 mutant gliomas is incompletely understood. To characterize 5hmC in IDH1 mutant gliomas further, we examine 5hmC in a cohort of IDH1 mutant and wild-type high-grade gliomas (HGG) using a quantitative locus-specific approach. Regions demonstrating high 5hmC abundance and differentially hydroxymethylated regions (DHMR) enrich for enhancers implicated in glioma pathogenesis...
February 10, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29428949/elevated-global-dna-methylation-is-not-exclusive-to-amyotrophic-lateral-sclerosis-and-is-also-observed-in-spinocerebellar-ataxia-types-1-and-2
#3
Hamid Hamzeiy, Doruk Savaş, Ceren Tunca, Nesli Ece Şen, Aslı Gündoğdu Eken, Irmak Şahbaz, Daniela Calini, Cinzia Tiloca, Nicola Ticozzi, Antonia Ratti, Vincenzo Silani, A Nazlı Başak
Adult-onset neurological disorders are caused and influenced by a multitude of different factors, including epigenetic modifications. Here, using an ELISA kit selected upon careful testing, we investigated global 5-methylcytosine (5-mC) levels in sporadic and familial amyotrophic lateral sclerosis (sALS and fALS), spinocerebellar ataxia types 1 and 2 (SCA1 and SCA2), Huntington's disease, Friedreich's ataxia, and myotonic dystrophy type 1. We report a significant elevation in global 5-mC levels of about 2-7% on average for sALS (p < 0...
February 9, 2018: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/29427306/impaired-fear-extinction-in-serotonin-transporter-knockout-rats-is-associated-with-increased-5-hydroxymethylcytosine-in-the-amygdala
#4
Ling Shan, Hang-Yuan Guo, Corina N A M van den Heuvel, Joop van Heerikhuize, Judith R Homberg
AIMS: One potential risk factor for posttraumatic stress disorder (PTSD) involves the low activity (short; s) allelic variant of the serotonin transporter-linked polymorphic region (5-HTTLPR), possibly due to reduced prefrontal control over the amygdala. Evidence shows that DNA methylation/demethylation is crucial for fear extinction in these brain areas and is associated with neuronal activation marker c-Fos expression. We hypothesized that impaired fear extinction in serotonin transporter knockout (5-HTT-/- ) rats is related to changes in DNA (de) methylation and c-Fos expression in the prefrontal cortex (PFC) and/or amygdala...
February 9, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29415265/oxidation-products-of-5-methyl-cytosine-are-decreased-in-senescent-cells-and-tissues-of-progeroid-mice
#5
Ewelina Zarakowska, Jolanta Czerwinska, Agnieszka Tupalska, Matt J Yousefzadeh, Siobhán Q Gregg, Claudette M St Croix, Laura J Niedernhofer, Marek Foksinski, Daniel Gackowski, Anna Szpila, Marta Starczak, Barbara Tudek, Ryszard Olinski
5-Hydroxymethylcytosine and 5-formylcytosine are stable DNA base modifications generated from 5-methylcytosine by the ten-eleven translocation protein family that function as epigenetic markers. 5-Hydroxymethyluracil may also be generated from thymine by ten-eleven translocation enzymes. Here, we asked if these epigenetic changes accumulate in senescent cells, since they are thought to be inversely correlated with proliferation. Testing this in ERCC1-XPF-deficient cells and mice also enabled discovery if these DNA base changes are repaired by nucleotide excision repair...
February 3, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29410709/genomic-5-mc-contents-in-peripheral-blood-leukocytes-were-independent-protective-factors-for-coronary-artery-disease-with-a-specific-profile-in-different-leukocyte-subtypes
#6
Qianyun Deng, Wei Huang, Chunyan Peng, Jiajia Gao, Zuhua Li, Xueping Qiu, Na Yang, Bifeng Yuan, Fang Zheng
Background: Alterations in DNA methylation are demonstrated in atherosclerosis pathogenesis. However, changing rules of global DNA methylation and hydroxymethylation in peripheral blood leukocytes (PBLs) and different blood cell subtypes of coronary artery disease (CAD) patients are still inconclusive, and much less is known about mechanisms underlying. Results: We recruited 265 CAD patients and 270 healthy controls with genomic DNA from PBLs, of which 50 patients and 50 controls were randomly chosen with DNA from isolated neutrophils, lymphocytes and monocytes, and RNA from PBLs...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29407727/dna-redox-modulations-and-global-dna-methylation-in-bipolar-disorder-effects-of-sex-smoking-and-illness-state
#7
Deniz Ceylan, Gustavo Scola, Zeliha Tunca, Cameron Isaacs-Trepanier, Güneş Can, Ana C Andreazza, L Trevor Young, Ayşegül Özerdem
DNA redox modulations and methylation have been associated with bipolar disorder (BD) pathophysiology. We aimed to investigate DNA redox modulation and global DNA methylation and demethylation levels in patients with BD during euthymia, mania or depression in comparison to non-psychiatric controls. The roles of sex and smoking as susceptibility factors for DNA redox modulations and global DNA methylation and demethylation were also explored. Levels of 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were assessed in DNA samples of 75 patients with DSM-IV BD type I (37 euthymic, 18 manic, 20 depressive) in comparison to 60 non-psychiatric controls...
December 27, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/29406813/reading-cytosine-modifications-within-chromatin
#8
Elise A Mahé, Thierry Madigou, Gilles Salbert
Zinc-finger and homeodomain transcription factors have been shown in vitro to bind to recognition motifs containing a methylated CpG. However, accessing these motifs in vivo might be seriously impeded by the inclusion of DNA in nucleosomes and by the condensed structure adopted by chromatin formed on methylated DNA. Here, we discuss how oxidation of 5-methylcytosine into 5-hydroxymethylcytosine could provide the initial destabilizing clue for such transcription factors to get access to nucleosomal DNA and read epigenetic information...
February 6, 2018: Transcription
https://www.readbyqxmd.com/read/29394393/decoding-the-dynamic-dna-methylation-and-hydroxymethylation-landscapes-in-endodermal-lineage-intermediates-during-pancreatic-differentiation-of-hesc
#9
Jia Li, Xinwei Wu, Yubin Zhou, Minjung Lee, Lei Guo, Wei Han, William Mo, Wen-Ming Cao, Deqiang Sun, Ruiyu Xie, Yun Huang
Dynamic changes in DNA methylation and demethylation reprogram transcriptional outputs to instruct lineage specification during development. Here, we applied an integrative epigenomic approach to unveil DNA (hydroxy)methylation dynamics representing major endodermal lineage intermediates during pancreatic differentiation of human embryonic stem cells (hESCs). We found that 5-hydroxymethylcytosine (5hmC) marks genomic regions to be demethylated in the descendent lineage, thus reshaping the DNA methylation landscapes during pancreatic lineage progression...
January 31, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29382202/sulfinate-based-selective-labelling-of-5-hydroxy-methylcytosine-application-to-biotin-pull-down-assay
#10
Wu Qiong, Suyog Madhav Amrutkar, Fangwei Shao
We developed an enzyme-free, chemical method to selectively label the epigenetic base, 5-hydroxymethylcytosine (5-hmC) with versatile sulfinate reagents in aqueous solvent under mild reaction conditions. This method allows efficient single step conjugation of biotin to 5-hmC site in DNA for enrichment and pull down assays.
January 31, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29369386/epigenetic-modifications-of-cytosine-biophysical-properties-regulation-and-function-in-mammalian-dna
#11
REVIEW
Jack S Hardwick, Andrew N Lane, Tom Brown
To decode the function and molecular recognition of several recently discovered cytosine derivatives in the human genome - 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine - a detailed understanding of their effects on the structural, chemical, and biophysical properties of DNA is essential. Here, we review recent literature in this area, with particular emphasis on features that have been proposed to enable the specific recognition of modified cytosine bases by DNA-binding proteins. These include electronic factors, modulation of base-pair stability, flexibility, and radical changes in duplex conformation...
January 25, 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29364877/tet2-promotes-pathogen-infection-induced-myelopoiesis-through-mrna-oxidation
#12
Qicong Shen, Qian Zhang, Yang Shi, Qingzhu Shi, Yanyan Jiang, Yan Gu, Zhiqing Li, Xia Li, Kai Zhao, Chunmei Wang, Nan Li, Xuetao Cao
Varieties of RNA modification form the epitranscriptome for post-transcriptional regulation. 5-Methylcytosine (5-mC) is a sparse RNA modification in messenger RNA (mRNA) under physiological conditions. The function of RNA 5-hydroxymethylcytosine (5-hmC) oxidized by ten-eleven translocation (Tet) proteins in Drosophila has been revealed more recently. However, the turnover and function of 5-mC in mammalian mRNA have been largely unknown. Tet2 suppresses myeloid malignancies mostly in an enzymatic activity-dependent manner, and is important in resolving inflammatory response in an enzymatic activity-independent way...
February 1, 2018: Nature
https://www.readbyqxmd.com/read/29357837/detecting-tf-mirna-gene-network-based-modules-for-5hmc-and-5mc-brain-samples-a-intra-and-inter-species-case-study-between-human-and-rhesus
#13
Ujjwal Maulik, Sagnik Sen, Saurav Mallik, Sanghamitra Bandyopadhyay
BACKGROUND: Study of epigenetics is currently a high-impact research topic. Multi stage methylation is also an area of high-dimensional prospect. In this article, we provide a new study (intra and inter-species study) on brain tissue between human and rhesus on two methylation cytosine variants based data-profiles (viz., 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) samples) through TF-miRNA-gene network based module detection. RESULTS: First of all, we determine differentially 5hmC methylated genes for human as well as rhesus for intra-species analysis, and differentially multi-stage methylated genes for inter-species analysis...
January 22, 2018: BMC Genetics
https://www.readbyqxmd.com/read/29353135/copper-induces-expression-and-methylation-changes-of-early-development-genes-in-crassostrea-gigas-embryos
#14
Rossana Sussarellu, Morgane Lebreton, Julien Rouxel, Farida Akcha, Guillaume Rivière
Copper contamination is widespread along coastal areas and exerts adverse effects on marine organisms such as mollusks. In the Pacific oyster, copper induces severe developmental abnormalities during early life stages; however, the underlying molecular mechanisms are largely unknown. This study aims to better understand whether the embryotoxic effects of copper in Crassostrea gigas could be mediated by alterations in gene expression, and the putative role of DNA methylation, which is known to contribute to gene regulation in early embryo development...
January 3, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29343074/understanding-the-influence-of-antipsychotic-drugs-on-global-methylation-events-and-its-relevance-in-treatment-response
#15
Babu Swathy, Koramannil R Saradalekshmi, Indu V Nair, Chandrasekharan Nair, Moinak Banerjee
AIM: The present study intends to evaluate whether antipsychotic drugs can modulate the host epigenome and if so whether drug-induced epigenetic modulation can explain the heterogeneity in drug response. METHODS: Present study was conducted in in vitro cells and significance of these in vitro observations was further evaluated in a clinical setting, between drug responsive and nonresponsive schizophrenia patients. A number of DNA modifications were assessed at global level using 5-methylcytosine, 5-hydroxymethylcytosine and 5-formylcytosine followed by evaluating the expression of epigenetic modifier genes and their crosstalk with miRNAs...
January 18, 2018: Epigenomics
https://www.readbyqxmd.com/read/29324752/tet-protein-function-during-drosophila-development
#16
Fei Wang, Svetlana Minakhina, Hiep Tran, Neha Changela, Joseph Kramer, Ruth Steward
The TET (Ten-eleven translocation) 1, 2 and 3 proteins have been shown to function as DNA hydroxymethylases in vertebrates and their requirements have been documented extensively. Recently, the Tet proteins have been shown to also hydroxylate 5-methylcytosine in RNA. 5-hydroxymethylcytosine (5hmrC) is enriched in messenger RNA but the function of this modification has yet to be elucidated. Because Cytosine methylation in DNA is barely detectable in Drosophila, it serves as an ideal model to study the biological function of 5hmrC...
2018: PloS One
https://www.readbyqxmd.com/read/29290954/wee1-epigenetically-modulates-5-hmc-levels-by-py37-h2b-dependent-regulation-of-idh2-gene-expression
#17
Nupam P Mahajan, Pavani Malla, Shambhavi Bhagwat, Vasundhara Sharma, Amod Sarnaik, Jongphil Kim, Shari Pilon-Thomas, Jeffery Weber, Kiran Mahajan
Epigenetic signaling networks dynamically regulate gene expression to maintain cellular homeostasis. Previously, we uncovered that WEE1 phosphorylates histone H2B at tyrosine 37 (pY37-H2B) to negatively regulate global histone transcriptional output. Although pY37-H2B is readily detected in cancer cells, its functional role in pathogenesis is not known. Herein, we show that WEE1 deposits the pY37-H2B marks within the tumor suppressor gene, isocitrate dehydrogenase 2 (IDH2), to repress transcription in multiple cancer cells, including glioblastoma multiforme (GBMs), melanoma and prostate cancer...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29286410/an-engineered-split-tet2-enzyme-for-chemical-inducible-dna-hydroxymethylation-and-epigenetic-remodeling
#18
Minjung Lee, Yubin Zhou, Yun Huang
DNA methylation is a stable and heritable epigenetic modification in the mammalian genome and is involved in regulating gene expression to control cellular functions. The reversal of DNA methylation, or DNA demethylation, is mediated by the ten-eleven translocation (TET) protein family of dioxygenases. Although it has been widely reported that aberrant DNA methylation and demethylation are associated with developmental defects and cancer, how these epigenetic changes directly contribute to the subsequent alteration in gene expression or disease progression remains unclear, largely owing to the lack of reliable tools to accurately add or remove DNA modifications in the genome at defined temporal and spatial resolution...
December 18, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29285192/ten-eleven-translocation-1-dysfunction-reduces-5-hydroxymethylcytosine-expression-levels-in-gastric-cancer-cells
#19
Kuo-Chiang Wang, Chi-Hsiang Kang, Chung-Yu Tsai, Nan-Hua Chou, Ya-Ting Tu, Guan-Cheng Li, Hing-Chung Lam, Shiuh-Inn Liu, Po-Min Chang, Yan-Hwai Lin, Kuo-Wang Tsai
A sixth base, 5-hydroxymethylcytosine (5hmC), is formed by the oxidation of 5-methylcytosine (5mC) via the catalysis of the ten-eleven translocation (TET) protein family in cells. Expression levels of 5hmC are frequently depleted during carcinogenesis. However, the detailed mechanisms underlying the depletion of 5hmC expression in gastric cancer cells remains unclear, and further research is required. The present study examined the expression levels of 5mC and 5hmC and the expression levels of TET1 and TET2 in gastric cancer tissues using immunohistochemistry...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29277934/fam20c-could-be-targeted-by-tet1-to-promote-odontoblastic-differentiation-potential-of-human-dental-pulp-cells
#20
Qimeng Li, Baicheng Yi, Zhihui Feng, Runsha Meng, Cheng Tian, Qiong Xu
OBJECTIVES: Ten-eleven translocation 1 (TET1) is a DNA methylcytosine (mC) dioxygenase discovered recently that can convert 5-mC into 5-hydroxymethylcytosine (5hmC). We previously reported that TET1 promotes odontoblastic differentiation of human dental pulp cells (hDPCs). The gene encoding the family with sequence similarity 20, member C (FAM20C) protein, is a potential TET1 target and showed demethylation during odontoblastic differentiation of hDPCs in our previous study. This study aimed to explore whether TET1-mediated hydroxymethylation could activate the FAM20C gene, thereby regulating hDPC differentiation...
December 25, 2017: Cell Proliferation
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