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Dna hydroxymethylation

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https://www.readbyqxmd.com/read/27924045/a-novel-method-for-the-simultaneous-identification-of-methylcytosine-and-hydroxymethylcytosine-at-a-single-base-resolution
#1
Yuki Kawasaki, Yukiko Kuroda, Isao Suetake, Shoji Tajima, Fumitoshi Ishino, Takashi Kohda
Since the discovery of oxidative demethylation of methylcytosine (mC) by Tet enzymes, an analytical method has been urgently needed that would enable the identification of mC and hydroxymethylcytosine (hmC) at the single base resolution level, because their roles in gene regulation are quite different from each other. However, the bisulfite sequencing method, the gold standard for DNA methylation analysis at present, does not distinguish them. Recently reported alternative methods, such as oxBS-seq and TAB-seq, are not even capable of determining mC and hmC simultaneously...
October 24, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27911668/association-of-5-hydroxymethylation-and-5-methylation-of-dna-cytosine-with-tissue-specific-gene-expression
#2
V K Chaithanya Ponnaluri, Kenneth C Ehrlich, Guoqiang Zhang, Michelle Lacey, Douglas Johnston, Sriharsa Pradhan, Melanie Ehrlich
Differentially methylated or hydroxymethylated regions (DMRs) in mammalian DNA are often associated with tissue-specific gene expression but the functional relationships are still being unraveled. To elucidate these relationships, we studied 16 human genes containing myogenic DMRs by analyzing profiles of their epigenetics and transcription and quantitatively assaying 5-hydroxymethylcytosine (5 hmC) and 5-methylcytosine (5 mC) at specific sites in these genes in skeletal muscle (SkM), myoblasts, heart, brain, and diverse other samples...
December 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27911399/tools-to-study-the-role-of-architectural-protein-hmgb1-in-the-processing-of-helix-distorting-site-specific-dna-interstrand-crosslinks
#3
Anirban Mukherjee, Karen M Vasquez
High mobility group box 1 (HMGB1) protein is a non-histone architectural protein that is involved in regulating many important functions in the genome, such as transcription, DNA replication, and DNA repair. HMGB1 binds to structurally distorted DNA with higher affinity than to canonical B-DNA. For example, we found that HMGB1 binds to DNA interstrand crosslinks (ICLs), which covalently link the two strands of the DNA, cause distortion of the helix, and if left unrepaired can cause cell death. Due to their cytotoxic potential, several ICL-inducing agents are currently used as chemotherapeutic agents in the clinic...
November 10, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27905578/2-r-fluorinated-mc-hmc-fc-and-cac-triphosphates-are-substrates-for-dna-polymerases-and-tet-enzymes
#4
A S Schröder, E Parsa, K Iwan, F R Traube, M Wallner, S Serdjukow, T Carell
A deeper investigation of the chemistry that occurs on the newly discovered epigenetic DNA bases 5-hydroxymethyl-(hmdC), 5-formyl-(fdC), and 5-carboxy-deoxycytidine (cadC) requires chemical tool compounds, which are able to dissect the different potential reaction pathways in cells. Here we report that the 2'-(R)-fluorinated derivatives F-hmdC, F-fdC, and F-cadC, which are resistant to removal by base excision repair, are good substrates for DNA polymerases and TET enzymes. This result shows that the fluorinated compounds are ideal tool substances to investigate potential C-C-bond cleaving reactions in the context of active demethylation...
December 1, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27903986/adult-t-cell-leukemia-aggressivenness-correlates-with-loss-of-both-5-hydroxymethylcytosine-and-tet2-expression
#5
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/27903915/max-is-an-epigenetic-sensor-of-5-carboxylcytosine-and-is-altered-in-multiple-myeloma
#6
Dongxue Wang, Hideharu Hashimoto, Xing Zhang, Benjamin G Barwick, Sagar Lonial, Lawrence H Boise, Paula M Vertino, Xiaodong Cheng
The oncogenic transcription factor MYC and its binding partner MAX regulate gene expression by binding to DNA at enhancer-box (E-box) elements 5'-CACGTG-3'. In mammalian genomes, the central E-box CpG has the potential to be methylated at the 5-position of cytosine (5mC), or to undergo further oxidation to the 5-hydroxymethyl (5hmC), 5-formyl (5fC), or 5-carboxyl (5caC) forms. We find that MAX exhibits the greatest affinity for a 5caC or unmodified C-containing E-box, and much reduced affinities for the corresponding 5mC, 5hmC or 5fC forms...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27886677/differences-in-global-dna-methylation-of-testicular-seminoma-are-not-associated-with-changes-in-histone-modifications-clinical-prognosis-braf-mutations-or-gene-expression
#7
Louise Holm Pedersen, John E Nielsen, Gedske Daugaard, Thomas V O Hansen, Ewa Rajpert-De Meyts, Kristian Almstrup
Testicular germ cell tumours of young adults are comprised of a heterogeneous group of non-seminomas and a homogeneous group of seminomas. While the majority of seminomas retain a hypo-methylated genome, a small fraction displays a highly methylated genome, resembling hyper-methylated non-seminomas. It is well established from e.g. melanoma, colorectal and thyroid cancer that a methylated phenotype can be correlated to prognosis and can be related to BRAF mutations. In the present study we investigated the global methylation level in 67 seminomas and classified them as hypo-methylated, intermediate, patchy and hyper-methylated, respectively...
November 2016: Cancer Genetics
https://www.readbyqxmd.com/read/27879253/the-yin-yang-dynamics-of-dna-methylation-is-the-key-regulator-for-smooth-muscle-cell-phenotype-switch-and-vascular-remodeling
#8
Jianhui Zhuang, Peipei Luan, Hailing Li, Kai Wang, Pei Zhang, Yawei Xu, Wenhui Peng
OBJECTIVE: DNA methylation plays an important role in chronic diseases such as atherosclerosis, yet the mechanisms are poorly understood. The objective of our study is to indicate the regulatory mechanisms of DNA methylation in vascular smooth muscle cells (VSMCs) and its roles in atherosclerosis. APPROACH AND RESULTS: In ApoE(-/-) mice fed a Western diet, DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, significantly attenuated atherosclerotic lesions (20...
November 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27878282/the-importance-of-mitochondrial-folate-enzymes-in-human-colorectal-cancer
#9
Masaaki Miyo, Masamitsu Konno, Hugh Colvin, Naohiro Nishida, Jun Koseki, Koichi Kawamoto, Kenta Tsunekuni, Junichi Nishimura, Taishi Hata, Ichiro Takemasa, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori, Hideshi Ishii
Folate plays a pivotal role in the one-carbon metabolism needed for methylation reactions, nucleotide synthesis, and DNA repair. Although folate metabolism was recently shown to be associated with carcinogenesis in some solid tumors, the importance of folate metabolism in colorectal cancer remains unclear. In the present investigation we found that expression of three mitochondrial folate metabolic enzymes, serine hydroxymethyl transferase (SHMT2), methylenetetrahydrofolate dehydrogenase (MTHFD2) and aldehyde dehydrogenase 1 family member L2 (ALDH1L2), were upregulated in human colorectal tumor tissues compared to normal tissues...
November 22, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27856615/epigenetic-regulation-of-intestinal-stem-cells-by-tet1-mediated-dna-hydroxymethylation
#10
Rinho Kim, Karyn L Sheaffer, Inchan Choi, Kyoung-Jae Won, Klaus H Kaestner
Methylated cytosines are associated with gene silencing. The ten-eleven translocation (TET) hydroxylases, which oxidize methylated cytosines to 5-hydroxymethylcytosine (5hmC), are essential for cytosine demethylation. Gene silencing and activation are critical for intestinal stem cell (ISC) maintenance and differentiation, but the potential role of TET hydroxylases in these processes has not yet been examined. Here, we generated genome-wide maps of the 5hmC mark in ISCs and their differentiated progeny. Genes with high levels of hydroxymethylation in ISCs are strongly associated with Wnt signaling and developmental processes...
November 17, 2016: Genes & Development
https://www.readbyqxmd.com/read/27849519/dna-methylation-directs-genomic-localization-of-mbd2-and-mbd3-in-embryonic-stem-cells
#11
Sarah J Hainer, Kurtis N McCannell, Jun Yu, Ly-Sha Ee, Lihua J Zhu, Oliver J Rando, Thomas G Fazzio
Cytosine methylation is an epigenetic and regulatory mark that functions in part through recruitment of chromatin remodeling complexes containing methyl-CpG binding domain (MBD) proteins. Two MBD proteins, Mbd2 and Mbd3, were previously shown to bind methylated or hydroxymethylated DNA, respectively; however, both of these findings have been disputed. Here, we investigated this controversy using experimental approaches and re-analysis of published data and find no evidence for methylation-independent functions of Mbd2 or Mbd3...
November 16, 2016: ELife
https://www.readbyqxmd.com/read/27830979/dietary-and-supplemental-maternal-methyl-group-donor-intake-and-cord-blood-dna-methylation
#12
Sara Pauwels, Manosij Ghosh, Radu Corneliu Duca, Bram Bekaert, Kathleen Freson, Inge Huybrechts, Sabine Langie, Gudrun Koppen, Roland Devlieger, Lode Godderis
Maternal nutrition is critically involved in the development and health of the fetus. We evaluated maternal methyl-group donor intake through diet (methionine, betaine, choline, folate) and supplementation (folic acid) before and during pregnancy in relation to global DNA methylation and hydroxymethylation and gene specific (IGF2 DMR, DNMT1, LEP, RXRA) cord blood methylation. A total of 115 mother-infant pairs were enrolled in the MAternal Nutrition and Offspring's Epigenome (MANOE) study. The intake of methyl-group donors was assessed using a food-frequency questionnaire...
November 10, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27829228/tet2-functions-as-a-resistance-factor-against-dna-methylation-acquisition-during-epstein-barr-virus-infection
#13
Hiroe Namba-Fukuyo, Sayaka Funata, Keisuke Matsusaka, Masaki Fukuyo, Bahityar Rahmutulla, Yasunobu Mano, Masashi Fukayama, Hiroyuki Aburatani, Atsushi Kaneda
Extensive DNA methylation is observed in gastric cancer with Epstein-Barr virus (EBV) infection, and EBV infection is the cause to induce this extensive hypermethylaton phenotype in gastric epithelial cells. However, some 5' regions of genes do not undergo de novo methylation, despite the induction of methylation in surrounding regions, suggesting the existence of a resistance factor against DNA methylation acquisition. We conducted an RNA-seq analysis of gastric epithelial cells with and without EBV infection and found that TET family genes, especially TET2, were repressed by EBV infection at both mRNA and protein levels...
November 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27814653/mitochondrial-genome-and-epigenome-two-sides-of-the-same-coin
#14
Patrizia D'Aquila, Alberto Montesanto, Francesco Guarasci, Giuseppe Passarino, Dina Bellizzi
The involvement of mitochondrial content, structure and function as well as of the mitochondrial genome (mtDNA) in cell biology, by participating in the main processes occurring in the cells, has been a topic of intense interest for many years. More specifically, the progressive accumulation of variations in mtDNA of post-mitotic tissues represents a major contributing factor to both physiological and pathological phenotypes. Recently, an epigenetic overlay on mtDNA genetics is emerging, as demonstrated by the implication of the mitochondrial genome in the regulation of the intracellular epigenetic landscape being itself object of epigenetic modifications...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27812888/5-hmf-attenuates-striatum-oxidative-damage-via-nrf2-are-signaling-pathway-following-transient-global-cerebral-ischemia
#15
Bai-Liu Ya, Hong-Fang Li, Hai-Ying Wang, Fei Wu, Qing Xin, Hong-Ju Cheng, Wen-Juan Li, Na Lin, Zai-Hua Ba, Ru-Juan Zhang, Qian Liu, Ya-Nan Li, Bo Bai, Feng Ge
Recent studies have shown 5-hydroxymethyl-2-furfural (5-HMF) has favorable biological effects, and its neuroprotection in a variety of neurological diseases has been noted. Our previous study showed that treatment of 5-HMF led to protection against permanent global cerebral ischemia. However, the underlying mechanisms in cerebral ischemic injury are not fully understood. This study was conducted to investigate the neuroprotective effect of 5-HMF and elucidate the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway mechanism in the striatum after transient global cerebral ischemia...
November 3, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27809363/peptide-stabilized-fluorescent-silver-nanoclusters-solid-phase-synthesis-and-screening
#16
Simon Gregersen, Tom Vosch, Knud J Jensen
Few-atom silver nanoclusters (AgNCs) can exhibit strong fluorescence; however, they require ligands to prevent aggregation into larger nanoparticles. Fluorescent AgNCs in biopolymer scaffolds have so far mainly been synthesized in solution, and peptides have only found limited use compared to DNA. Herein, we demonstrate how solid-phase methods can increase throughput dramatically in peptide ligand screening and in initial evaluation of fluorescence intensity and chemical stability of peptide-stabilized AgNCs (P-AgNCs)...
November 3, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27803663/environmental-enrichment-modified-epigenetic-mechanisms-in-samp8-mouse-hippocampus-by-reducing-oxidative-stress-and-inflammaging-and-achieving-neuroprotection
#17
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/27787562/the-role-of-dna-methylation-in-the-metabolic-memory-phenomenon-associated-with-the-continued-progression-of-diabetic-retinopathy
#18
Manish Mishra, Renu A Kowluru
Purpose: Clinical and experimental studies have shown that diabetic retinopathy progression does not halt after termination of hyperglycemia, suggesting a "metabolic memory" phenomenon. DNA is highly dynamic, and cytosine methylation changes can last for several years. In diabetes, DNA methylation regulates expression of many genes associated with retinal mitochondrial homeostasis. Our aim was to investigate the role of DNA methylation in the metabolic memory. Methods: Reversal of 4 days of 20 mM glucose by 4 to 8 days of 5 mM glucose, in the presence/absence of Dnmt inhibitor (5-aza-2'-deoxycytidine), was investigated on DNA methylation and its machinery in human retinal endothelial cells...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27776477/short-and-long-term-effects-of-56-fe-irradiation-on-cognition-and-hippocampal-dna-methylation-and-gene-expression
#19
Soren Impey, Timothy Jopson, Carl Pelz, Amanuel Tafessu, Fatema Fareh, Damian Zuloaga, Tessa Marzulla, Lara-Kirstie Riparip, Blair Stewart, Susanna Rosi, Mitchell S Turker, Jacob Raber
BACKGROUND: Astronauts are exposed to (56)Fe ions that may pose a significant health hazard during and following prolonged missions in deep space. We showed previously that object recognition requiring the hippocampus, a structure critical for cognitive function, is affected in 2-month-old mice irradiated with (56)Fe ions. Here we examined object recognition in 6-month-old mice irradiated with (56)Fe ions, a biological age more relevant to the typical ages of astronauts. Moreover, because the mechanisms mediating the detrimental effects of (56)Fe ions on hippocampal function are unclear, we examined changes in hippocampal networks involved in synaptic plasticity and memory, gene expression, and epigenetic changes in cytosine methylation (5mC) and hydroxymethylation (5hmC) that could accompany changes in gene expression...
October 24, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27770360/analysis-of-dna-hydroxymethylation-using-colorimetric-assay
#20
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
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