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https://www.readbyqxmd.com/read/27903915/max-is-an-epigenetic-sensor-of-5-carboxylcytosine-and-is-altered-in-multiple-myeloma
#1
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/27880907/tet3-mediated-dna-demethylation-contributes-to-the-direct-conversion-of-fibroblast-to-functional-neuron
#2
Juan Zhang, Shuangquan Chen, Dongming Zhang, Zixiao Shi, Hong Li, Tongbiao Zhao, Baoyang Hu, Qi Zhou, Jianwei Jiao
The direct conversion of somatic cells to neurons by bypassing the multipotent cell state may be a powerful approach for personalized medicine. In addition to neuronal transcription factors and multiple small molecules, we find that epigenetic modification also contributes to the direct conversion of fibroblasts to neurons. Here, we show that Tet3, a DNA dioxygenase, can rapidly and efficiently convert fibroblasts directly into functional neurons. The induced neurons (iNs) express pan and mature neuronal markers such as Tuj1, Synapsin, and neuronal nuclei (NeuN)...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27863519/tet-dependent-regulation-of-retrotransposable-elements-in-mouse-embryonic-stem-cells
#3
Lorenzo de la Rica, Özgen Deniz, Kevin C L Cheng, Christopher D Todd, Cristina Cruz, Jonathan Houseley, Miguel R Branco
BACKGROUND: Ten-eleven translocation (TET) enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable elements (TEs), which make up nearly half of the mouse and human genomes. Epigenetic mechanisms controlling TEs have the potential to affect their mobility and to drive the co-adoption of TEs for the benefit of the host. RESULTS: We performed a detailed investigation of the role of TET enzymes in the regulation of TEs in mouse embryonic stem cells (ESCs)...
November 18, 2016: Genome Biology
https://www.readbyqxmd.com/read/27856615/epigenetic-regulation-of-intestinal-stem-cells-by-tet1-mediated-dna-hydroxymethylation
#4
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/27851806/5-hydroxymethylcytosine-precedes-loss-of-cpg-methylation-in-enhancers-and-genes-undergoing-activation-in-cardiomyocyte-maturation
#5
David K Kranzhöfer, Ralf Gilsbach, Björn A Grüning, Rolf Backofen, Thomas G Nührenberg, Lutz Hein
BACKGROUND: Cardiomyocytes undergo major changes in DNA methylation during maturation and transition to a non-proliferative state after birth. 5'-hydroxylation of methylated cytosines (5hmC) is not only involved in DNA loss of CpG methylation but is also thought to be an epigenetic mark with unique distribution and functions. Here, we sought to get insight into the dynamics of 5'-hydroxymethylcytosine in newborn and adult cardiomyocytes. METHODS: Cardiomyocyte nuclei from newborn and adult C57BL/6 mice were purified by flow cytometric sorting...
2016: PloS One
https://www.readbyqxmd.com/read/27846738/association-of-tet1-expression-with-colorectal-cancer-progression
#6
Yiping Tian, Feixia Pan, Xiaohui Sun, Meifu Gan, Aifen Lin, Dandan Zhang, Yimin Zhu, Maode Lai
OBJECTIVE: The ten-eleven translocation (TET) proteins, as methylcytosine dioxygenases, catalyze 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). The altered expression of TET1 disrupts the balance between DNA methylation and demethylation. This alteration has been reported to be associated with carcinogenesis in various malignancies. The aim of the present study was to investigate changes in expression and the role of TET1 in colorectal cancer (CRC). MATERIAL AND METHODS: A total of 109 CRC patients who underwent radical surgical colon resection were enrolled...
November 16, 2016: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/27835592/epigenetic-upregulation-of-arl4c-due-to-dna-hypomethylation-in-the-3-untranslated-region-promotes-tumorigenesis-of-lung-squamous-cell-carcinoma
#7
Shinsuke Fujii, Keiko Shinjo, Shinji Matsumoto, Takeshi Harada, Satoshi Nojima, Sunao Sato, Yu Usami, Satoru Toyosawa, Eiichi Morii, Yutaka Kondo, Akira Kikuchi
ADP-ribosylation factor (ARF)-like 4c (ARL4C) expression, induced by a combination of Wnt/β-catenin and EGF/Ras signaling, has been demonstrated to form epithelial morphogenesis. ARL4C overexpression, due to Wnt/β-catenin and EGF/Ras signaling alterations, was involved in tumorigenesis. It was also reported that ARL4C expression correlates with DNA hypomethylation in the 3'-untranslated region (UTR) of ARL4C gene during lymphogenesis. The current study was conducted to investigate the expression and functions of ARL4C due to DNA hypomethylation in lung and tongue cancers...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27835581/regulatory-landscape-and-clinical-implication-of-mbd3-in-human-malignant-glioma
#8
Yi Cui, Jian Li, Ling Weng, Sara E Wirbisky, Jennifer L Freeman, Jingping Liu, Qing Liu, Xianrui Yuan, Joseph Irudayaraj
In this article we inspect the roles and functions of the methyl-CpG-binding domain protein 3 (MBD3) in human malignant glioma, to assess its potential as an epigenetic biomarker for prognosis. The regulatory effects of MBD3 on glioma transcriptome were first profiled by high-throughput microarray. Our results indicate that MBD3 is involved in both transcriptional activation and repression. Furthermore, MBD3 fine-controls a spectrum of proteins critical for cellular metabolism and proliferation, thereby contributing to an exquisite anti-glioma network...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27826843/structure-and-function-of-tet-enzymes
#9
Xiaotong Yin, Yanhui Xu
Mammalian DNA methylation mainly occurs at the carbon-C5 position of cytosine (5mC). TET enzymes were discovered to successively oxidize 5mC to 5-hydromethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). TET enzymes and oxidized 5mC derivatives play important roles in various biological and pathological processes, including regulation of DNA demethylation, gene transcription, embryonic development, and oncogenesis. In this chapter, we will discuss the discovery of TET-mediated 5mC oxidation and the structure, function, and regulation of TET enzymes...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27821816/tet-methylcytosine-dioxygenase-2-inhibits-atherosclerosis-via-upregulation-of-autophagy-in-apoe-mice
#10
Juan Peng, Qin Yang, A-Fang Li, Rong-Qing Li, Zuo Wang, Lu-Shan Liu, Zhong Ren, Xi-Long Zheng, Xiao-Qing Tang, Guo-Hua Li, Zhi-Han Tang, Zhi-Sheng Jiang, Dang-Heng Wei
Tet methylcytosine dioxygenase 2 (TET2) mediates the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). The loss of TET2 is associated with advanced atherosclerotic lesions. Our previous study showed that TET2 improves endothelial cell function by enhancing endothelial cell autophagy. Accordingly, this study determined the role of TET2 in atherosclerosis and potential mechanisms. In ApoE-/- mice fed high-fat diet, TET2 overexpression markedly decreased atherosclerotic lesions with uniformly increased level of 5hmC and decreased level of 5mC in genomic DNA...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27805801/tet1-mediated-oxidation-of-5-formylcytosine-5fc-to-5-carboxycytosine-5cac-in-rna
#11
Maria Basanta-Sanchez, Rui Wang, Zhenzhen Liu, Xiaohan Ye, Minyong Li, Xiaodong Shi, Paul Agris, Yubin Zhou, Yun Huang, Jia Sheng
It has been revealed recently that 5-methylcytosine (5mC) in mRNA, similar as in DNA, can also be oxidized to produce 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC), implying the potential regulatory roles of this post-transcriptional RNA modification. In this study, we demonstrate the in vitro oxidation of 5fC to 5-carboxycytidine (5caC) by the catalytic domain of mammalian ten-eleven translocation enzyme (TET1) in different RNA contexts. We observed that this oxidation process has very low sequence dependence and can take place in single stranded, double stranded or hairpin forms of RNA sequences, although the overall conversion yields are low...
November 2, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27776477/short-and-long-term-effects-of-56-fe-irradiation-on-cognition-and-hippocampal-dna-methylation-and-gene-expression
#12
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/27762133/replacement-of-2-deoxycytidine-by-2-deoxycytidine-analogues-in-the-e-coli-genome
#13
Angad P Mehta, Han Li, Sean A Reed, Lubica Supekova, Tsotne Javahishvili, Peter G Schultz
Several modified bases have been observed in the genomic DNA of bacteriophages, prokaryotes, and eukaryotes that play a role in restriction systems and/or epigenetic regulation. In our efforts to understand the consequences of replacing a large fraction of a canonical nucleoside with a modified nucleoside, we previously replaced around 75% of thymidine (T) with 5'-hydroxymethyl-2'-deoxyuridine (5hmU) in the Escherichia coli genome. In this study, we engineered the pyrimidine nucleotide biosynthetic pathway using T4 bacteriophage genes to achieve approximately 63% replacement of 2'-deoxycytidine (dC) with 5-hydroxymethyl-2'-deoxycytidine (5hmC) in the E...
November 2, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27738314/loss-of-uhrf2-expression-is-associated-with-human-neoplasia-promoter-hypermethylation-decreased-5-hydroxymethylcytosine-and-high-proliferative-activity
#14
Huarui Lu, Sweta Bhoopatiraju, Hongbo Wang, Nolan P Schmitz, Xiaohong Wang, Matthew J Freeman, Colleen L Forster, Michael R Verneris, Michael A Linden, Timothy C Hallstrom
Ubiquitin-like with PHD and ring finger domains 2 (UHRF2) binds to 5-hydroxymethylcytosine (5hmC), a DNA base involved in tissue development, but it is unknown how their distribution compares with each other in normal and malignant human tissues. We used IHC on human tumor specimens (160 from 19 tumor types) or normal tissue to determine the expression and distribution of UHRF2, Ki-67, and 5hmC. We also examined UHRF2 expression in cord blood progenitors and compared its expression to methylation status in 6 leukemia cell lines and 15 primary human leukemias...
October 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27737935/whole-genome-analysis-of-the-methylome-and-hydroxymethylome-in-normal-and-malignant-lung-and-liver
#15
Xin Li, Yun Liu, Tal Salz, Kasper D Hansen, Andrew Feinberg
DNA methylation at the 5-position of cytosine (5mC) is an epigenetic modification that regulates gene expression and cellular plasticity in development and disease. The ten-eleven translocation (TET) gene family oxidizes 5mC to 5-hydroxymethylcytosine (5hmC), providing an active mechanism for DNA demethylation, and it may also provide its own regulatory function. Here we applied oxidative bisulfite sequencing to generate whole-genome DNA methylation and hydroxymethylation maps at single-base resolution in human normal liver and lung as well as paired tumor tissues...
October 13, 2016: Genome Research
https://www.readbyqxmd.com/read/27733056/the-elusive-role-of-5-hydroxymethylcytosine
#16
Moshe Szyf
5'-hydroxymethylcytosine (5hmC) is a variant of the common covalent epigenetic modification of DNA 5'-methylcytosine (5mC). Although the presence of this modified base in mammalian DNA has been recognized for several decades, it has recently gained center stage as a suspected intermediate in enzymatic active demethylation of 5mC. The role of 5hmC remains elusive in spite of a large body of studies. It is proposed that 5hmC is a variant of the 5mC epigenetic signal and is involved in epigenetic regulation of gene function...
October 13, 2016: Epigenomics
https://www.readbyqxmd.com/read/27729528/retinol-and-ascorbate-drive-erasure-of-epigenetic-memory-and-enhance-reprogramming-to-na%C3%A3-ve-pluripotency-by-complementary-mechanisms
#17
Timothy Alexander Hore, Ferdinand von Meyenn, Mirunalini Ravichandran, Martin Bachman, Gabriella Ficz, David Oxley, Fátima Santos, Shankar Balasubramanian, Tomasz P Jurkowski, Wolf Reik
Epigenetic memory, in particular DNA methylation, is established during development in differentiating cells and must be erased to create naïve (induced) pluripotent stem cells. The ten-eleven translocation (TET) enzymes can catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further oxidized derivatives, thereby actively removing this memory. Nevertheless, the mechanism by which the TET enzymes are regulated, and the extent to which they can be manipulated, are poorly understood...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27720826/the-ciona-intestinalis-cleavage-clock-is-independent-of-dna-methylation
#18
Miho M Suzuki, Tomoko Mori, Noriyuki Satoh
The initiation of embryonic gene expression in ascidian embryos appears to be tightly regulated by the number of DNA replication cycles. DNA methylation is thought to contribute to the clock mechanism that counts the rounds of DNA replication. We used mass spectrometry and whole genome bisulfite sequencing to characterize DNA methylation changes that occur in early developmental stages of the ascidian, Ciona intestinalis. We found that global DNA methylation in early Ciona development was static, and a base-wise comparison between the genomes of consecutive developmental stages found no DNA demethylation that was related to zygotic gene activation...
October 5, 2016: Genomics
https://www.readbyqxmd.com/read/27682401/glucosylation-mediated-rolling-circle-amplification-combined-with-a-qpcr-assay-for-the-detection-of-5-hydroxymethylcytosine
#19
Di Liu, Chao Zhao, Hailin Wang
The detection of 5-hydroxymethylcytosine (5hmC), a newly recognized epigenetic mark, is essential to its functional study. Here, an efficient and simple two-step-amplification method to detect 5hmC mediated by glucosylation is reported, which combines rolling circle amplification (RCA) and a quantitative polymerase chain reaction (qPCR). In the first step RCA, the glucosylated 5hmC (5ghmC), but not 5hmC, 5-methylcytosine (5mC) or cytosine (C) bases, could directly and specifically inhibit the activity of phi29 DNA polymerase, resulting in less RCA product compared to that using C-/5mC-/5hmC-containing templates...
2016: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
https://www.readbyqxmd.com/read/27633378/chiral-antioxidant-based-gold-nanoclusters-reprogram-dna-epigenetic-patterns
#20
Yue Ma, Hualin Fu, Chunlei Zhang, Shangli Cheng, Jie Gao, Zhen Wang, Weilin Jin, João Conde, Daxiang Cui
Epigenetic modifications sit 'on top of' the genome and influence DNA transcription, which can force a significant impact on cellular behavior and phenotype and, consequently human development and disease. Conventional methods for evaluating epigenetic modifications have inherent limitations and, hence, new methods based on nanoscale devices are needed. Here, we found that antioxidant (glutathione) chiral gold nanoclusters induce a decrease of 5-hydroxymethylcytosine (5hmC), which is an important epigenetic marker that associates with gene transcription regulation...
2016: Scientific Reports
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