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Dna hydroxymethylation

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https://www.readbyqxmd.com/read/29158345/stable-oxidative-cytosine-modifications-accumulate-in-cardiac-mesenchymal-cells-from-type2-diabetes-patients-rescue-by-alpha-ketoglutarate-and-tet-tdg-functional-reactivation
#1
Francesco Spallotta, Chiara Cencioni, Sandra Atlante, Davide Garella, Mattia Cocco, Mattia Mori, Raffaella Mastrocola, Carsten Künne, Stefan Günther, Simona Nanni, Valerio Azzimato, Sven Zukunft, Angela Kornberger, Duran Sueruen, Frank Schnutgen, Harald von Melchner, Antonella Di Stilo, Manuela Aragno, Maarten Braspenning, Wim Van Criekinge, Miles J De Blasio, Rebecca H Ritchie, Germana Zaccagnini, Fabio Martelli, Antonella Farsetti, Ingrid Fleming, Thomas Braun, Andres Beiras-Fernandez, Bruno Botta, Massimo Collino, Massimo Bertinaria, Andreas M Zeiher, Carlo Gaetano
Rationale: Human cardiac mesenchymal cells (CMSCs) are a therapeutically-relevant primary cell population. Diabetes compromises CMSC function as consequence of metabolic alterations and incorporation of stable epigenetic changes. Objective: To investigate the role of α-ketoglutarate (αKG) in the epi-metabolic control of DNA demethylation in CMSCs. Methods and Results: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing and gene specific GC methylation detection revealed an accumulation of 5mC, 5hmC and 5fC in the genomic DNA of human CMSCs isolated from diabetic (D) donors (D-CMSCs)...
November 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/29156615/clinical-significance-of-measuring-global-hydroxymethylation-of-white-blood-cell-dna-in-prostate-cancer-comparison-to-psa-in-a-pilot-exploratory-study
#2
Alin Grelus, Dragos V Nica, Imola Miklos, Valerica Belengeanu, Ioan Ioiart, Cristina Popescu
This is the first study investigating the clinical relevance of 5-hydroxymethylcytosine (5hmC) in genomic DNA from white blood cells (WBC) in the context of prostate cancer (PCa) and other prostate pathologies. Using an enzyme-linked immunosorbent assay, we identified significantly different distributions of patients with low and elevated 5hmC content in WBC DNA across controls and patients with prostate cancer (PCa), atypical small acinar proliferation (ASAP), and benign prostatic hyperplasia (BPH). The measured values were within the normal range for most PCa patients, while the latter category was predominant for ASAP...
November 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29138806/effect-of-bis-hydroxymethyl-alkanoate-curcuminoid-derivative-mth-3-on-cell-cycle-arrest-apoptotic-and-autophagic-pathway-in-triple-negative-breast-adenocarcinoma-mda-mb-231-cells-an-in-vitro-study
#3
Ling-Chu Chang, Min-Tsang Hsieh, Jai-Sing Yang, Chi-Cheng Lu, Fuu-Jen Tsai, Je-Wei Tsao, Yu-Jen Chiu, Sheng-Chu Kuo, Kuo-Hsiung Lee
Curcumin has been shown to exert potential antitumor activity in vitro and in vivo involved in multiple signaling pathways. However, the application of curcumin is still limited because of its poor hydrophilicity and low bio-availability. In the present study, we investigated the therapeutic effects of a novel and water soluble bis(hydroxymethyl) alkanoate curcuminoid derivative, MTH-3, on human breast adenocarcinoma MDA-MB-231 cells. This study investigated the effect of MTH-3 on cell viability, cell cycle and induction of autophagy and apoptosis in MDA-MB-231 cells...
November 14, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29130343/defining-baseline-epigenetic-landscapes-in-the-rat-liver
#4
John P Thomson, Raffaele Ottaviano, Roland Buesen, Jonathan G Moggs, Michael Schwarz, Richard R Meehan
Characterization of the hepatic epigenome following exposure to chemicals and therapeutic drugs provides novel insights into toxicological and pharmacological mechanisms, however appreciation of genome-wide inter- and intra-strain baseline epigenetic variation, particularly in under-characterized species such as the rat is limited. Material & methods: To enhance the utility of epigenomic endpoints safety assessment, we map both DNA modifications (5-methyl-cytosine and 5-hydroxymethyl-cytosine) and enhancer related chromatin marks (H3K4me1 and H3K27ac) across multiple male and female rat livers for two important outbred laboratory rat strains (Sprague-Dawley and Wistar)...
November 13, 2017: Epigenomics
https://www.readbyqxmd.com/read/29113959/age-related-epigenetic-changes-in-hippocampal-subregions-of-four-animal-models-of-alzheimer-s-disease
#5
Roy Lardenoije, Daniël L A van den Hove, Monique Havermans, Anne van Casteren, Kevin X Le, Roberta Palmour, Cynthia A Lemere, Bart P F Rutten
Both aging and Alzheimer's disease (AD) are associated with widespread epigenetic changes, with most evidence suggesting global hypomethylation in AD. It is, however, unclear how these age-related epigenetic changes are linked to molecular aberrations as expressed in animal models of AD. Here, we investigated age-related changes of epigenetic markers of DNA methylation and hydroxymethylation in a range of animal models of AD, and their correlations with amyloid plaque load. Three transgenic mouse models, including the J20, APP/PS1dE9 and 3xTg-AD models, as well as Caribbean vervets (a non-transgenic non-human primate model of AD) were investigated...
November 4, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29113828/downregulation-of-bdh2-modulates-iron-homeostasis-and-promotes-dna-demethylation-in-cd4-t-cells-of-systemic-lupus-erythematosus
#6
Ming Zhao, Meng-Ying Li, Xiao-Fei Gao, Su-Jie Jia, Ke-Qin Gao, Yin Zhou, Hui-Hui Zhang, Yi Huang, Jing Wang, Hai-Jing Wu, Qian-Jin Lu
DNA hypomethylation plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Here we investigated whether 3-hydroxy butyrate dehydrogenase 2 (BDH2), a modulator of intracellular iron homeostasis, was involved in regulating DNA hypomethylation and hyper-hydroxymethylation in lupus CD4(+) T cells. Our results showed that BDH2 expression was decreased, intracellular iron was increased, global DNA hydroxymethylation level was elevated, while methylation level was reduced in lupus CD4(+) T cells compared with healthy controls...
November 4, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29100458/dna-methylation-hydroxymethylation-in-melanoma
#7
REVIEW
Siqi Fu, Haijing Wu, Huiming Zhang, Christine G Lian, Qianjin Lu
Melanoma is a malignant tumor of melanocytes and is considered to be the most aggressive cancer among all skin diseases. The pathogenesis of melanoma has not been well documented, which may restrict the research and development of biomarkers and therapies. To date, several genetic and epigenetic factors have been identified as contributing to the development and progression of melanoma. Besides the findings on genetic susceptibilities, the recent progress in epigenetic studies has revealed that loss of the DNA hydroxymethylation mark, 5-hydroxymethylcytosine (5-hmC), along with high levels of DNA methylation at promoter regions of several tumor suppressor genes in melanoma, may serve as biomarkers for melanoma...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29092933/integrating-dna-methylation-and-hydroxymethylation-data-with-the-mint-pipeline
#8
Raymond G Cavalcante, Snehal Patil, Yongseok Park, Laura S Rozek, Maureen A Sartor
DNA methylation (5mC) plays important roles in mammalian development, oncogenesis, treatment response, and responses to the environment. DNA hydroxymethylation (5hmC) is also an informative epigenetic mark with distinct roles in regulation and cancer. Gold-standard, widely used technologies (bisulfite conversion, followed by deep sequencing) cannot distinguish between 5mC and 5hmC. Therefore, additional experiments are required to differentiate the two marks, and in silico methods are needed to analyze, integrate, and interpret these data...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/29091992/transcriptome-wide-analysis-suggests-that-temporal-changes-in-the-relative-contributions-of-hyperplasia-hypertrophy-and-apoptosis-underlie-liver-growth-in-pregnant-mice
#9
Leonie R Price, Karen A Lillycrop, Nicola A Irvine, Mark A Hanson, Graham C Burdge
Maternal liver undergoes structural and metabolic changes during pregnancy to meet the demands of the developing fetus. In rodents, this involves increased liver weight, but the mechanism remains unclear. To address this, we analysed the histology, gene expression and DNA methylation of livers of non-pregnant and pregnant C57/BL6 mice. Gestational liver growth in pregnant mice was accompanied by increased hepatocyte area and lower cell density (days 14,18). Expression of cell proliferation markers was increased on days 14 and 18...
October 30, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29069286/dna-hydroxymethylation-levels-are-altered-in-blood-cells-from-down-syndrome-persons-enrolled-in-the-mark-age-project
#10
Fabio Ciccarone, Elisabetta Valentini, Marco Malavolta, Michele Zampieri, Maria Giulia Bacalini, Roberta Calabrese, Tiziana Guastafierro, Anna Reale, Claudio Franceschi, Miriam Capri, Nicolle Breusing, Tilman Grune, María Moreno-Villanueva, Alexander Bürkle, Paola Caiafa
Down syndrome (DS) is caused by the presence of part or an entire extra copy of chromosome 21, a phenomenon that can cause a wide spectrum of clinically defined phenotypes of the disease. Most of the clinical signs of DS are typical of the ageing process including dysregulation of immune system. Beyond the causative genetic defect, DS persons display epigenetic alterations, particularly aberrant DNA methylation patterns that can contribute to the heterogeneity of the disease. In the present work we investigated the levels of 5-hydroxymethylcytosine (5hmC) and of the TET dioxygenase enzymes, which are involved in DNA demethylation processes and are often deregulated in pathological conditions as well as in ageing...
October 21, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29051587/dna-methylation-and-hydroxymethylation-analyses-of-the-active-line-1-subfamilies-in-mice
#11
Yui Murata, Miki Bundo, Junko Ueda, Mie Kubota-Sakashita, Kiyoto Kasai, Tadafumi Kato, Kazuya Iwamoto
Retrotransposon long interspersed nuclear element-1 (LINE-1) occupies a large proportion of the mammalian genome, comprising approximately 100,000 genomic copies in mice. Epigenetic status of the 5' untranslated region (5'-UTR) of LINE-1 is critical for its promoter activity. DNA methylation levels in the 5'-UTR of human active LINE-1 subfamily can be measured by well-established methods, such as a pyrosequencing-based assay. However, because of the considerable sequence and structural diversity in LINE-1 among species, methods for such assays should be adapted for the species of interest...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29045485/alterations-in-the-placental-methylome-with-maternal-obesity-and-evidence-for-metabolic-regulation
#12
Kohzoh Mitsuya, Ashley N Parker, Lu Liu, Jianhua Ruan, Margreet C M Vissers, Leslie Myatt
The inflammatory and metabolic derangements of obesity in pregnant women generate an adverse intrauterine environment, increase pregnancy complications and adverse fetal outcomes and program the fetus for obesity and metabolic syndrome in later life. We hypothesized that epigenetic modifications in placenta including altered DNA methylation/hydroxymethylation may mediate these effects. Term placental villous tissue was collected following cesarean section from lean (prepregnancy BMI<25) or obese (BMI>30) women...
2017: PloS One
https://www.readbyqxmd.com/read/29036598/global-dna-methylation-analysis-reveals-mir-214-3p-contributes-to-cisplatin-resistance-in-pediatric-intracranial-nongerminomatous-malignant-germ-cell-tumors
#13
Tsung-Han Hsieh, Yun-Ru Liu, Ting-Yu Chang, Muh-Lii Liang, Hsin-Hung Chen, Hsei-Wei Wang, Yun Yen, Tai-Tong Wong
Background: Pediatric central nervous system germ cell tumors (CNSGCTs) are rare and heterogeneous neoplasms, and they can be divided into germinomas and nongerminomatous GCTs (NGGCTs). NGGCTs are further subdivided into mature teratomas and nongerminomatous malignant GCTs (NGMGCTs). Clinical outcomes suggest that NGMGCTs have poor prognosis and survival, and that they require more extensive radiotherapy and adjuvant chemotherapy. However, the mechanisms underlying this difference are still unclear...
October 3, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28993426/effect-of-diabetes-status-and-hyperglycemia-on-global-dna-methylation-and-hydroxymethylation
#14
Jairo Arturo Pinzón-Cortés, Angelina Perna-Chaux, Nicolás Steven Rojas-Villamizar, Angélica Díaz-Basabe, Diana Carolina Polanía-Villanueva, María Fernanda Jácome, Carlos Olimpo Mendivil, Helena Groot, Valeriano López-Segura
Type 2 diabetes mellitus (T2DM) is characterized by oxidative stress that could lead to chronic micro- and macrovascular complications. We hypothesized that some of the target organ damage is mediated by oxidative alterations in epigenetic mechanisms involving DNA methylation (5mC) and DNA hydroxymethylation (5hmC). We analyzed global DNA methylation and hydroxymethylation in peripheral blood cells in well-controlled and poorly controlled patients with T2DM and compared them with healthy controls. We also analyzed microarrays of DNA methylation and gene expression of other important tissues in the context of diabetes from the GEO database repository and then compared these results with our experimental gene expression data...
November 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28945496/mouse-olfactory-bulb-methylome-and-hydroxymethylome-maps-reveal-noncanonical-active-turnover-of-dna-methylation
#15
Qin Ma, Huan Lu, Ziying Xu, Yuanyuan Zhou, Weimin Ci
Hydroxylation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by TET enzymes presents a particular regulatory mechanism in the mammalian brain. However, although methylation and hydroxymethylation of cytosines in non-CpG contexts have been reported, these mechanisms remain poorly understood. Here, we applied TAB-seq and oxBS-seq selectively to detect 5hmC and 5mC at base resolution in olfactory bulb derived from female mice. We found that active turnover of 5mC to 5hmC occurred in both CpG and non-CpG contexts...
September 25, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28944423/differential-dna-hydroxymethylation-in-human-uterine-leiomyoma-cells-depending-on-the-phase-of-menstrual-cycle-and-presence-of-med12-gene-mutations
#16
A S Kol'tsova, A A Pendina, O A Efimova, A N Kaminskaya, A V Tikhonov, N S Osinovskaya, I Yu Sultanov, N Yu Shved, M I Kakhiani, V S Baranov
Using immunofluorescence with specific antibodies, we analyzed DNA hydroxymethylation in uncultured cells from 25 human uterine leiomyomas considering the menstrual cycle phase during surgery and the presence of MED12 gene mutations. It was found that each tumor node had specific DNA hydroxymethylation level that did not depend on the presence of mutations in MED12 gene, but depended on the phase of menstrual cycle. The degree of DNA hydroxymethylation was significantly lower in cells of leiomyomas excised during the luteal phase compared to the follicular phase (p=0...
September 25, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28941008/non-canonical-bases-in-the-genome-the-regulatory-information-layer-in-dna
#17
Thomas Carell, Matthias Q Kurz, Markus Müller, Martin Rossa, Fabio Spada
The sequence of the four canonical bases dA, dC, dG and dT forming two defined Watson-Crick base pairs (dT:dA, dG:dC), held together by H-bonding, establish the sequence information in the DNA double strand. The faithful replication of the sequence information during cell division, the transcription of the DNA information into RNA and the final translation of the sequence information into proteins is the basis for life on earth. Multicellular organisms developed the concept of specialized cells that perform specific functions...
September 21, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28934725/prenatal-exposure-to-mercury-associations-with-global-dna-methylation-and-hydroxymethylation-in-cord-blood-and-in-childhood
#18
Andres Cardenas, Sheryl L Rifas-Shiman, Lode Godderis, Radu-Corneliu Duca, Ana Navas-Acien, Augusto A Litonjua, Dawn L DeMeo, Kasey J Brennan, Chitra J Amarasiriwardena, Marie-France Hivert, Matthew W Gillman, Emily Oken, Andrea A Baccarelli
BACKGROUND: Mercury is a global pollutant, and prenatal exposure is associated with adverse health effects. To date, no studies have evaluated the association between prenatal mercury exposure and DNA hydroxymethylation, an epigenetic modification important for tissue differentiation and embryonic development. OBJECTIVES: We sought to evaluate the association between prenatal mercury exposure and offspring global DNA methylation and hydroxymethylation at birth and test for persistence of the association in childhood...
August 29, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28927804/synthesis-of-damaged-dna-containing-the-oxidative-lesion-3-oxothymidine
#19
Mel F Bedi, Weiye Li, Taylor Gutwald, Amanda C Bryant-Friedrich
Oxidative events that take place during regular oxygen metabolism can lead to the formation of organic or inorganic radicals. The interaction of these radicals with macromolecules in the organism and with DNA in particular is suspected to lead to apoptosis, DNA lesions and cell damage. Independent generation of DNA lesions resulting from oxidative damage is used to promote the study of their effects on biological systems. An efficient synthesis of oligodeoxyribonucleotides (ODNs) containing the oxidative damage lesion 3'-oxothymidine has been accomplished via incorporation of C3'-hydroxymethyl thymidine as its corresponding 5'-phosphoramidite...
September 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28926578/tet-mediated-dna-hydroxymethylation-regulates-retinal-neurogenesis-by-modulating-cell-extrinsic-signaling-pathways
#20
Pawat Seritrakul, Jeffrey M Gross
DNA hydroxymethylation has recently been shown to play critical roles in regulating gene expression and terminal differentiation events in a variety of developmental contexts. However, little is known about its function during eye development. Methylcytosine dioxygenases of the Tet family convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), an epigenetic mark thought to serve as a precursor for DNA demethylation and as a stable mark in neurons. Here, we report a requirement for Tet activity during zebrafish retinal neurogenesis...
September 2017: PLoS Genetics
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