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https://www.readbyqxmd.com/read/28538185/regulation-of-active-dna-demethylation-through-rar-mediated-recruitment-of-a-tet-tdg-complex
#1
Haider M Hassan, Bart Kolendowski, Majdina Isovic, Kerstin Bose, Helen J Dranse, Arthur V Sampaio, T Michael Underhill, Joseph Torchia
Retinoic acid (RA) plays important roles in development, growth, and homeostasis through regulation of the nuclear receptors for RA (RARs). Herein, we identify Hypermethylated in Cancer 1 (Hic1) as an RA-inducible gene. HIC1 encodes a tumor suppressor, which is often silenced by promoter hypermethylation in cancer. Treatment of cells with an RAR agonist causes a rapid recruitment of an RAR/RXR complex consisting of TDG, the lysine acetyltransferase CBP, and TET 1/2 to the Hic1 promoter. Complex binding coincides with a transient accumulation of 5fC/5caC and concomitant upregulation of Hic1 expression, both of which are TDG dependent...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28360182/simultaneous-mapping-of-active-dna-demethylation-and-sister-chromatid-exchange-in-single-cells
#2
Xiaoji Wu, Azusa Inoue, Tsukasa Suzuki, Yi Zhang
To understand mammalian active DNA demethylation, various methods have been developed to map the genomic distribution of the demethylation intermediates 5-formylcysotine (5fC) and 5-carboxylcytosine (5caC). However, the majority of these methods requires a large number of cells to begin with. In this study, we describe low-input methylase-assisted bisulfite sequencing (liMAB-seq ) and single-cell MAB-seq (scMAB-seq), capable of profiling 5fC and 5caC at genome scale using ∼100 cells and single cells, respectively...
March 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28348165/combinatorial-dna-methylation-codes-at-repetitive-elements
#3
Christophe Papin, Abdulkhaleg Ibrahim, Stephanie Le Gras, Amandine Velt, Bernard Jost, Isabelle Stoll, Hervé Menoni, Christian Bronner, Stefan Dimitrov, Ali Hamiche
DNA methylation is an essential epigenetic modification, present in both unique DNA sequences and repetitive elements, but its exact function in repetitive elements remains obscure. Here, we describe the genome-wide comparative analysis of the 5mC, 5hmC, 5fC and 5caC profiles of repetitive elements in mouse embryonic fibroblasts and mouse embryonic stem cells. We provide evidence for distinct and highly specific DNA methylation/oxidation patterns of the repetitive elements in both cell types, which mainly affect CA repeats and evolutionary conserved mouse-specific transposable elements including IAP-LTRs, SINEs B1m/B2m and L1Md-LINEs...
March 27, 2017: Genome Research
https://www.readbyqxmd.com/read/28343982/single-cell-5-formylcytosine-landscapes-of-mammalian-early-embryos-and-escs-at-single-base-resolution
#4
Chenxu Zhu, Yun Gao, Hongshan Guo, Bo Xia, Jinghui Song, Xinglong Wu, Hu Zeng, Kehkooi Kee, Fuchou Tang, Chengqi Yi
Active DNA demethylation in mammals involves ten-eleven translocation (TET) family protein-mediated oxidation of 5-methylcytosine (5mC). However, base-resolution landscapes of 5-formylcytosine (5fC) (an oxidized derivative of 5mC) at the single-cell level remain unexplored. Here, we present "CLEVER-seq" (chemical-labeling-enabled C-to-T conversion sequencing), which is a single-cell, single-base resolution 5fC-sequencing technology, based on biocompatible, selective chemical labeling of 5fC and subsequent C-to-T conversion during amplification and sequencing...
May 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28316809/crystal-structure-and-hydrogen-bonding-patterns-in-5-fluoro-cytosinium-picrate
#5
Marimuthu Mohana, Packianathan Thomas Muthiah, Colin D McMillen
In the crystal structure of the title compound, 5-fluoro-cytosinium picrate, C4H5FN3O(+)·C6H2N3O7(-), one N heteroatom of the 5-fluoro-cytosine (5FC) ring is protonated. The 5FC ring forms a dihedral angle of 19.97 (11)° with the ring of the picrate (PA(-)) anion. In the crystal, the 5FC(+) cation inter-acts with the PA(-) anion through three-centre N-H⋯O hydrogen bonds, forming two conjoined rings having R2(1)(6) and R1(2)(6) motifs, and is extended by N-H⋯O hydrogen bonds and C-H⋯O inter-actions into a two-dimensional sheet structure lying parallel to (001)...
March 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28267381/dynamics-of-5-carboxylcytosine-during-hepatic-differentiation-potential-general-role-for-active-demethylation-by-dna-repair-in-lineage-specification
#6
Lara C Lewis, Peggy Cho Kiu Lo, Jeremy M Foster, Nan Dai, Ivan R Corrêa, Paulina M Durczak, Gary Duncan, Ashley Ramsawhook, Guruprasad Padur Aithal, Chris Denning, Nicholas R F Hannan, Alexey Ruzov
Patterns of DNA methylation (5-methylcytosine, 5mC) are rearranged during differentiation contributing to the regulation of cell type-specific gene expression. TET proteins oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be recognized and excised from DNA by thymine-DNA glycosylase (TDG) followed by the subsequent incorporation of unmodified cytosine into the abasic site via the base excision repair (BER) pathway. We previously demonstrated that 5caC accumulates during lineage specification of neural stem cells (NSCs) suggesting that such active demethylation pathway is operational in this system; however, it is still unknown if TDG/BER-dependent demethylation is used during other types of cellular differentiation...
April 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28261325/technical-advances-in-global-dna-methylation-analysis-in-human-cancers
#7
REVIEW
Basudev Chowdhury, Il-Hoon Cho, Joseph Irudayaraj
Prototypical abnormalities of genome-wide DNA methylation constitute the most widely investigated epigenetic mechanism in human cancers. Errors in the cellular machinery to faithfully replicate the global 5-methylcytosine (5mC) patterns, commonly observed during tumorigenesis, give rise to misregulated biological pathways beneficial to the rapidly propagating tumor mass but deleterious to the healthy tissues of the affected individual. A growing body of evidence suggests that the global DNA methylation levels could serve as utilitarian biomarkers in certain cancer types...
2017: Journal of Biological Engineering
https://www.readbyqxmd.com/read/28131025/an-ultra-performance-liquid-chromatography-tandem-mass-spectrometry-method-for-the-therapeutic-drug-monitoring-of-isavuconazole-and-seven-other-antifungal-compounds-in-plasma-samples
#8
Balthazar Toussaint, Fanny Lanternier, Christian Woloch, Denis Fournier, Manon Launay, Eliane Billaud, Eric Dannaoui, Olivier Lortholary, Vincent Jullien
A new analytical method was developed for the routine Therapeutic Drug Monitoring of 8 antifungals compounds in 50μL of plasma: isavuconazole (ISZ), voriconazole (VRZ), posaconazole (PSZ), fluconazole (FCZ), caspofungin (CSF), flucytosine (5FC), itraconazole (ITZ) and its metabolite OH-itraconazole (OH-ITZ). After adding 50μL of the internal standard, which consisted in a mixture of the deuterated isotopes of the quantified compounds, the sample treatment consisted in a simple protein precipitation with 400μL of acetonitrile...
March 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28034675/crispr-cas9-mediated-sequential-editing-of-genes-critical-for-ookinete-motility-in-plasmodium-yoelii
#9
Cui Zhang, Han Gao, Zhenke Yang, Yuanyuan Jiang, Zhenkui Li, Xu Wang, Bo Xiao, Xin-Zhuan Su, Huiting Cui, Jing Yuan
CRISPR/Cas9 has been successfully adapted for gene editing in malaria parasites including Plasmodium falciparum and Plasmodium yoelii. However, the reported methods were limited to editing one gene at a time. In practice, it is often desired to modify multiple genetic loci in a parasite genome. Here we describe a CRISPR/Cas9 mediated genome editing method that allows successive modification of more than one gene in the genome of P. yoelii using an improved single-vector system (pYCm) we developed previously...
December 26, 2016: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/27915307/diversity-and-antifungal-drug-susceptibility-of-cryptococcus-isolates-in-thailand
#10
Navaporn Worasilchai, Marut Tangwattanachuleeporn, Kornvalee Meesilpavikkai, Claudia Folba, Mourine Kangogo, Uwe Groß, Michael Weig, Oliver Bader, Ariya Chindamporn
Yeasts of the Cryptococcus species complex are the causative agent of cryptococcosis, especially in human immunodeficiency virus (HIV) positive individuals. Cerebral or disseminated cryptococcosis has a very high mortality rate worldwide, including in Thailand. Additionally, an increasing rate of antifungal drug resistant cryptococcal isolates has been reported in several neighboring countries, complicating therapeutic approaches. To understand the situation of this infection in Thailand, we retrospectively investigated the molecular epidemiology and antifungal drug resistance in a collection of 74 clinical, 52 environmental and two veterinary isolates using the URA5-RFLP for typing and the EUCAST guideline for susceptibility testing...
December 3, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/27903915/max-is-an-epigenetic-sensor-of-5-carboxylcytosine-and-is-altered-in-multiple-myeloma
#11
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...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27826843/structure-and-function-of-tet-enzymes
#12
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/27805801/tet1-mediated-oxidation-of-5-formylcytosine-5fc-to-5-carboxycytosine-5cac-in-rna
#13
Maria Basanta-Sanchez, Rui Wang, Zhenzhen Liu, Xiaohan Ye, Minyong Li, Xiaodong Shi, Paul F Agris, Yubin Zhou, Yun Huang, Jia Sheng
It was recently revealed that 5-methylcytosine (5mC) in mRNA, similar to its behavior in DNA, can 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...
January 3, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27742099/species-diversity-of-aspergillus-section-versicolores-in-clinical-samples-and-antifungal-susceptibility
#14
João Paulo Zen Siqueira, Deanna A Sutton, Dania García, Josepa Gené, Pamela Thomson, Nathan Wiederhold, Josep Guarro
Aspergillus section Versicolores includes species of clinical relevance and many others that have been poorly studied but are occasionally found in clinical samples. The aim of this study was to investigate, using a multilocus phylogenetic approach, the spectrum of species of the section Versicolores and to determine their in vitro antifungal susceptibility. The study was based on a set of 77 clinical isolates from different USA medical centres, which had been previously identified as belonging to this section...
November 2016: Fungal Biology
https://www.readbyqxmd.com/read/27587669/luxglm-a-probabilistic-covariate-model-for-quantification-of-dna-methylation-modifications-with-complex-experimental-designs
#15
Tarmo Äijö, Xiaojing Yue, Anjana Rao, Harri Lähdesmäki
MOTIVATION: 5-methylcytosine (5mC) is a widely studied epigenetic modification of DNA. The ten-eleven translocation (TET) dioxygenases oxidize 5mC into oxidized methylcytosines (oxi-mCs): 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). DNA methylation modifications have multiple functions. For example, 5mC is shown to be associated with diseases and oxi-mC species are reported to have a role in active DNA demethylation through 5mC oxidation and DNA repair, among others, but the detailed mechanisms are poorly understood...
September 1, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27587280/analysis-of-the-machinery-and-intermediates-of-the-5hmc-mediated-dna-demethylation-pathway-in-aging-on-samples-from-the-mark-age-study
#16
Elisabetta Valentini, Michele Zampieri, Marco Malavolta, Maria Giulia Bacalini, Roberta Calabrese, Tiziana Guastafierro, Anna Reale, Claudio Franceschi, Antti Hervonen, Bernhard Koller, Jürgen Bernhardt, P Eline Slagboom, Olivier Toussaint, Ewa Sikora, Efstathios S Gonos, Nicolle Breusing, Tilman Grune, Eugène Jansen, Martijn E T Dollé, María Moreno-Villanueva, Thilo Sindlinger, Alexander Bürkle, Fabio Ciccarone, Paola Caiafa
Gradual changes in the DNA methylation landscape occur throughout aging virtually in all human tissues. A widespread reduction of 5-methylcytosine (5mC), associated with highly reproducible site-specific hypermethylation, characterizes the genome in aging. Therefore, an equilibrium seems to exist between general and directional deregulating events concerning DNA methylation controllers, which may underpin the age-related epigenetic changes. In this context, 5mC-hydroxylases (TET enzymes) are new potential players...
August 29, 2016: Aging
https://www.readbyqxmd.com/read/27585398/detection-of-modified-forms-of-cytosine-using-sensitive-immunohistochemistry
#17
Abdulkadir Abakir, Lee Wheldon, Andrew D Johnson, Patrick Laurent, Alexey Ruzov
Methylation of cytosine bases (5-methylcytosine, 5mC) occurring in vertebrate genomes is usually associated with transcriptional silencing. 5-hydroxylmethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) are the recently discovered modified cytosine bases produced by enzymatic oxidation of 5mC, whose biological functions remain relatively obscure. A number of approaches ranging from biochemical to antibody based techniques have been employed to study the genomic distribution and global content of these modifications in various biological systems...
August 16, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27557497/the-emerging-insights-into-catalytic-or-non-catalytic-roles-of-tet-proteins-in-tumors-and-neural-development
#18
REVIEW
Hao Lian, Wen-Bin Li, Wei-Lin Jin
The Ten-eleven translocation (TET) proteins have been recently identified as critical regulators in epigenetic modification, especially in the methylation of cytosine in DNA. TET-mediated DNA oxidation plays prominent roles in a wide variety of physiological and pathological processes, especially in tumor and neural development. TET proteins execute stepwise enzymatic conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). In addition to the more proverbial enzymatic role of TET proteins, TET proteins also possess non-enzymatic activity, through interacting with some epigenetic modifiers...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27466503/isocitrate-dehydrogenase-2-dysfunction-contributes-to-5-hydroxymethylcytosine-depletion-in-gastric-cancer-cells
#19
Nan-Hua Chou, Chung-Yu Tsai, Ya-Ting Tu, Kuo-Chiang Wang, Chi-Hsiang Kang, Po-Min Chang, Guan-Cheng Li, Hing-Chung Lam, Shiuh-Inn Liu, Kuo-Wang Tsai
The isocitrate dehydrogenase (IDH) family of enzymes comprises of the key functional metabolic enzymes in the Krebs cycle that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG). α-KG acts as a cofactor in the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). However, the relationship between 5hmC and IDH in gastric cancer remains unclear. Our study revealed that the 5hmC level was substantially lower and 5mC level was slightly higher in gastric cancer tissues; however, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) levels did not change significantly in these tissues...
August 2016: Anticancer Research
https://www.readbyqxmd.com/read/27461566/combined-treatment-based-on-lysomustine-administration-with-mesenchymal-stem-cells-expressing-cytosine-deaminase-therapy-leads-to-pronounced-murine-lewis-lung-carcinoma-growth-inhibition
#20
Lyudmila S Krassikova, Saida S Karshieva, Ivan B Cheglakov, Alexander V Belyavsky
BACKGROUND: The combination of stem cell-based gene therapy with chemotherapy comprises an advantageous strategy that results in a reduction of system toxicity effects and an improvement in the general efficacy of treatment. In the present study, we estimated the efficacy of adipose tissue-derived mesenchymal stem cells (AT-MSCs) expressing cytosine deaminase (CDA) combined with lysomustine chemotherapy in mice bearing late stage Lewis lung carcinoma (LLC). METHODS: Adipose tissue-derived mesenchymal stem cells were transfected with non-insert plasmid construct transiently expressing fused cytosine deaminase-uracil phosphoribosyltransferase protein (CDA/UPRT) or the same construct fused with Herpes Simplex Virus Type1 tegument protein VP22 (CDA/UPRT/VP22)...
September 2016: Journal of Gene Medicine
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