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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/27872906/sequence-specific-recognition-of-methylated-dna-by-an-engineered-transcription-activator-like-effector-protein
#2
Shogo Tsuji, Shiroh Futaki, Miki Imanishi
A 5mC-selective TALE-repeat was created by screening a TALE repeat library containing randomized amino acids at repeat variable diresidues and their neighboring residues. The new repeat showed high 5mC discrimination ability. An artificial TALE containing the new repeat activated an endogenous gene in a genomic methylation status-dependent manner.
November 22, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27859411/dna-demethylation-pathways-additional-players-and-regulators
#3
Matthias Bochtler, Agnieszka Kolano, Guo-Liang Xu
DNA demethylation can occur passively by "dilution" of methylation marks by DNA replication, or actively and independently of DNA replication. Direct conversion of 5-methylcytosine (5mC) to cytosine (C), as originally proposed, does not occur. Instead, active DNA methylation involves oxidation of the methylated base by ten-eleven translocations (TETs), or deamination of the methylated or a nearby base by activation induced deaminase (AID). The modified nucleotide, possibly together with surrounding nucleotides, is then replaced by the BER pathway...
November 16, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27852840/methyl-cytosine-based-immunoprecipitation-for-dna-methylation-analysis
#4
Paul M Lizardi, Qin Yan, Narendra Wajapeyee
In mammalian cells, DNA methylation at the 5-position of cytosine leads to recruitment of proteins that selectively recognize and bind 5-methylcytosine (5mC). Taking advantage of the structural identity of 5mC, various affinity purification-based protocols have been developed to enrich for either DNA that is modified by 5mC or proteins that recognize 5mC. In this protocol, an antibody against 5mC is used to immunoprecipitate the methylated DNA. The method can be scaled up to perform genome-wide DNA methylation analysis...
November 16, 2016: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/27852070/epigenetic-silencing-of-tet2-and-tet3-induces-an-emt-like-process-in-melanoma
#5
Fuxing Gong, Yu Guo, Yiqian Niu, Jiawei Jin, Xiaojuan Zhang, Xiaoqian Shi, Limeng Zhang, Runting Li, Longxin Chen, Runlin Z Ma
Epithelial-Mesenchymal Transition (EMT) is a critical step in the progression of cancer. Malignant melanoma, a cancer developed from pigmented melanocytes, metastasizes through an EMT-like process. Ten-eleven translocation (TET) enzymes, catalyzing the conversion of 5-methylcytosine (5mC) to 5-hydroxylmethylcytosine (5-hmC), are down regulated in melanoma. However, their roles in the progression and the EMT-like process of melanoma are not fully understood. Here we report that DNA methylation induced silencing of TET2 and TET3 are responsible for the EMT-like process and the metastasis of melanoma...
November 12, 2016: Oncotarget
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/27836605/optical-biosensing-strategies-for-dna-methylation-analysis
#7
REVIEW
Md Nazmul Islam, Sharda Yadav, Md Hakimul Haque, Ahmed Munaz, Farhadul Islam, Md Shahriar Al Hossain, Vinod Gopalan, Alfred K Lam, Nam-Trung Nguyen, Muhammad J A Shiddiky
DNA methylation is an epigenetic modification of DNA, where a methyl group is added at the fifth carbon of the cytosine base to form 5 methyl cytosine (5mC) without altering the DNA sequences. It plays important roles in regulating many cellular processes by modulating key genes expression. Alteration in DNA methylation patterns becomes particularly important in the aetiology of different diseases including cancers. Abnormal methylation pattern could contribute to the pathogenesis of cancer either by silencing key tumor suppressor genes or by activating oncogenes...
October 19, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27826843/structure-and-function-of-tet-enzymes
#8
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/27826837/genetic-studies-on-mammalian-dna-methyltransferases
#9
Jiameng Dan, Taiping Chen
Cytosine methylation at the C5-position, generating 5-methylcytosine (5mC), is a DNA modification found in many eukaryotic organisms, including fungi, plants, invertebrates, and vertebrates, albeit its levels vary greatly in different organisms. In mammals, cytosine methylation occurs predominantly in the context of CpG dinucleotides, with the majority (60-80 %) of CpG sites in their genomes being methylated. DNA methylation plays crucial roles in the regulation of chromatin structure and gene expression and is essential for mammalian development...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27825882/a-reusable-laser-wrapped-graphene-ag-array-based-sers-sensor-for-trace-detection-of-genomic-dna-methylation
#10
Lei Ouyang, Yaowu Hu, Lihua Zhu, Gary J Cheng, Joseph Irudayaraj
Methylation is an important epigenetic DNA modification that governs gene expression. The genomic level of methylated DNA and its derivatives may serve as important indicators for the initiation and progression of cancers among other diseases. In this effort we propose a new laser wrapped graphene-Ag array as a highly sensitive Surface-enhanced Raman spectroscopy (SERS) sensor for the detection of methylated DNA (5-methylcytosine, 5mC) and its oxidation derivatives namely 5-hydroxymethylcytosine (5-hmC) and 5-carboxylcytosine (5-caC)...
September 22, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27821816/tet-methylcytosine-dioxygenase-2-inhibits-atherosclerosis-via-upregulation-of-autophagy-in-apoe-mice
#11
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
#12
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/27797352/the-dna-demethylase-ros1-targets-genomic-regions-with-distinct-chromatin-modifications
#13
Kai Tang, Zhaobo Lang, Heng Zhang, Jian-Kang Zhu
The Arabidopsis ROS1/DEMETER family of 5-methylcytosine (5mC) DNA glycosylases are the first genetically characterized DNA demethylases in eukaryotes. However, the features of ROS1-targeted genomic loci are not well understood. In this study, we characterized ROS1 target loci in Arabidopsis Col-0 and C24 ecotypes. We found that ROS1 preferentially targets transposable elements (TEs) and intergenic regions. Compared with most TEs, ROS1-targeted TEs are closer to protein coding genes, suggesting that ROS1 may prevent DNA methylation spreading from TEs to nearby genes...
October 31, 2016: Nature Plants
https://www.readbyqxmd.com/read/27776477/short-and-long-term-effects-of-56-fe-irradiation-on-cognition-and-hippocampal-dna-methylation-and-gene-expression
#14
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/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/27724854/association-between-global-leukocyte-dna-methylation-and-cardiovascular-risk-in-postmenopausal-women
#18
Ramon Bossardi Ramos, Vitor Fabris, Sheila Bunecker Lecke, Maria Augusta Maturana, Poli Mara Spritzer
BACKGROUND: Genetic studies to date have not provided satisfactory evidence regarding risk polymorphisms for cardiovascular disease (CVD). Conversely, epigenetic mechanisms, including DNA methylation, seem to influence the risk of CVD and related conditions. Because postmenopausal women experience an increase in CVD, we set out to determine whether global DNA methylation was associated with cardiovascular risk in this population. METHODS: In this cross sectional study carried out in a university hospital, 90 postmenopausal women without prior CVD diagnosis (55...
October 10, 2016: BMC Medical Genetics
https://www.readbyqxmd.com/read/27712053/simultaneous-and-sensitive-detection-of-multi-site-5-methylcytosine-including-non-cpg-sites-at-single-5mc-resolution
#19
Shuang Rao, Yuqi Chen, Tingting Hong, Zhiyong He, Shan Guo, Han Lai, Ge Guo, Yuhao Du, Xiang Zhou
The methylation status of multiplexed methylcytosine sites can be simultaneously monitored by ligation-depended PCR assay. The ability of quantitative detection of multiplexed sites in one PCR reaction makes it a good choice for detecting methylation at both CpG and non-CpG sites for research and diagnosis of disease compared with others. The assay can determine as low as 20 aM methylated DNA and has been successfully applied to the genomic DNA sample derived from cancer cell lines.
October 7, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27685992/sequence-dependent-t-g-base-pair-opening-in-dna-double-helix-bound-by-cren7-a-chromatin-protein-conserved-among-crenarchaea
#20
Lei Tian, Zhenfeng Zhang, Hanqian Wang, Mohan Zhao, Yuhui Dong, Yong Gong
T:G base pair arising from spontaneous deamination of 5mC or polymerase errors is a great challenge for DNA repair of hyperthermophilic archaea, especially Crenarchaea. Most strains in this phylum lack the protein homologues responsible for the recognition of the mismatch in the DNA repair pathways. To investigate whether Cren7, a highly conserved chromatin protein in Crenarchaea, serves a role in the repair of T:G mispairs, the crystal structures of Cren7-GTAATTGC and Cren7-GTGATCGC complexes were solved at 2...
2016: PloS One
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