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Epigenetics: Official Journal of the DNA Methylation Society

Ornella Affinito, Giovanni Scala, Domenico Palumbo, Ermanno Florio, Antonella Monticelli, Gennaro Miele, Vittorio Enrico Avvedimento, Alessandro Usiello, Lorenzo Chiariotti, Sergio Cocozza
DNA methylation is often analyzed by reporting the average methylation degree of each cytosine. In this study, we used a single molecule methylation analysis in order to look at the methylation conformation of individual molecules. Using D-aspartate oxidase as a model gene, we performed an in-depth methylation analysis through the developmental stages of three different mouse tissues (brain, lung, and gut), where this gene undergoes opposite methylation destiny. This approach allowed us to track both methylation and demethylation processes at high resolution...
October 17, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Gordon Greville, Amanda McCann, Pauline M Rudd, Radka Saldova
Glycosylation is one of the most fundamental posttranslational modifications in cellular biology and has been shown to be epigenetically regulated. Understanding this process is important as the clinical use of epigenetic therapies such as DNA methyltransferase inhibitors are undergoing clinical trials for the treatment of ovarian and breast cancer. Previous work has demonstrated that altered glycosylation patterns are associated with aggressive disease in women presenting with breast and ovarian cancer. Moreover, the tumor microenvironment of hypoxia results in globally altered DNA methylation and is associated with aggressive cancer phenotypes and chemo-resistance, a feature integral to many cancers...
September 30, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Sebastian Meller, Lisa Zipfel, Heidrun Gevensleben, Jörn Dietrich, Jörg Ellinger, Michael Majores, Johannes Stein, Verena Sailer, Maria Jung, Glen Kristiansen, Dimo Dietrich
Molecular biomarkers may facilitate the distinction between aggressive and clinically insignificant prostate cancer (PCa), thereby potentially aiding individualized treatment. We analyzed cysteine dioxygenase 1 (CDO1) promoter methylation and mRNA expression in order to evaluate its potential as prognostic biomarker. CDO1 methylation and mRNA expression were determined in cell lines and formalin-fixed paraffin-embedded prostatectomy specimens from a first cohort of 300 PCa patients using methylation-specific qPCR and qRT-PCR...
September 30, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Andres Cardenas, Catherine Allard, Myriam Doyon, E Andres Houseman, Kelly M Bakulski, Patrice Perron, Luigi Bouchard, Marie-France Hivert
Cord blood is widely used as surrogate tissue in epigenome-wide association studies of prenatal conditions. Cell type composition variation across samples can be an important confounder of epigenome-wide association studies in blood that constitute a mixture of cells. We evaluated a newly developed cord blood reference panel to impute cell type composition from DNA methylation levels, including nucleated red blood cells (nRBCs). We estimated cell type composition from 154 unique cord blood samples with available DNA methylation data as well as direct measurements of nucleated cell types...
September 26, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Martin Schlensog, Lara Magnus, Timon Heide, Julian Eschenbruch, Florian Steib, Maximilian Tator, Vera Kloten, Michael Rose, Erik Noetzel, Nadine T Gaisa, Ruth Knüchel, Edgar Dahl
Secreted frizzled related protein 3 (SFRP3) contains a cysteine-rich domain (CRD) that shares homology with Frizzled CRD and regulates WNT signaling. Independent studies showed epigenetic silencing of SFRP3 in melanoma and hepatocellular carcinoma. Moreover, a tumor suppressive function of SFRP3 was shown in androgen-independent prostate and gastric cancer cells. The current study is the first to investigate SFRP3 expression and its potential clinical impact on non-small cell lung carcinoma (NSCLC). WNT signaling components present on NSCLC subtypes were preliminary elucidated by expression data of The Cancer Genome Atlas (TCGA)...
September 13, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Valentina Medici, Dorothy A Kieffer, Noreene M Shibata, Harpreet Chima, Kyoungmi Kim, Angela Canovas, Juan F Medrano, Alma D Islas-Trejo, Kusum K Kharbanda, Kristin Olson, Ruijun J Su, Mohammad S Islam, Raisa Syed, Carl L Keen, Amy Y Miller, John C Rutledge, Charles H Halsted, Janine M LaSalle
Wilson disease (WD), a genetic disorder affecting copper transport, is characterized by hepatic and neurological manifestations with variable and often unpredictable presentation. Global DNA methylation in liver was previously modified by dietary choline in tx-j mice, a spontaneous mutant model of WD. We therefore hypothesized that the WD phenotype and hepatic gene expression of tx-j offspring could be modified by maternal methyl supplementation during pregnancy. In an initial experiment, female tx-j mice or wild type mice were fed control or choline-supplemented diets two weeks prior to mating through embryonic day 17...
September 9, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Oriella Andresini, Agnese Ciotti, Marianna N Rossi, Cecilia Battistelli, Mariarosaria Carbone, Rossella Maione
The cdk inhibitor p57(kip2), encoded by the Cdkn1c gene, plays a critical role in mammalian development and in the differentiation of several tissues. Cdkn1c protein levels are carefully regulated via imprinting and other epigenetic mechanisms affecting both the promoter and distant regulatory elements, which restrict its expression to particular developmental phases or specific cell types. Inappropriate activation of these regulatory mechanisms leads to Cdkn1c silencing, causing growth disorders and cancer...
September 9, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Bénédicte L Tremblay, Frédéric Guénard, Benoît Lamarche, Louis Pérusse, Marie-Claude Vohl
Epigenetic factors such as DNA methylation are DNA alterations affecting gene expression that can convey environmental information through generations. Only a few studies have demonstrated epigenetic inheritance in humans. Our objective is to quantify genetic and common environmental determinants of familial resemblances in DNA methylation levels, using a family based sample. DNA methylation was measured in 48 French Canadians from 16 families as part of the GENERATION Study. We used the Illumina HumanMethylation450 BeadChip array to measure DNA methylation levels in blood leukocytes on 485,577 CpG sites...
September 9, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Anneleen Decock, Maté Ongenaert, Bram De Wilde, Bénédicte Brichard, Rosa Noguera, Frank Speleman, Jo Vandesompele
Stage 4S neuroblastoma (NB) is a special type of NB found in infants with metastases at diagnosis and is associated with an excellent outcome due to its remarkable capacity to undergo spontaneous regression. As genomics have not been able to explain this intriguing clinical presentation, we here aimed at profiling the DNA methylome of stage 4S NB to better understand this phenomenon. To this purpose, differential methylation analyses between International Neuroblastoma Staging System (INSS) stage 4S, stage 4 and stage 1/2 were performed, using methyl-CpG-binding domain (MBD) sequencing data of 14 stage 4S, 14 stage 4, and 13 stage 1/2 primary NB tumors (all MYCN non-amplified in order not to confound results)...
September 6, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Benjamin Goeppert, Christina Ernst, Constance Baer, Stephanie Roessler, Marcus Renner, Arianeb Mehrabi, Mohammadreza Hafezi, Anita Pathil, Arne Warth, Albrecht Stenzinger, Wilko Weichert, Marion Bähr, Rainer Will, Peter Schirmacher, Christoph Plass, Dieter Weichenhan
Cholangiocarcinoma (CC) is a rare malignancy of the extrahepatic or intrahepatic biliary tract with an outstanding poor prognosis. Non-surgical therapeutic regimens result in minimally improved survival of CC patients. Global genomic analyses identified a few recurrently mutated genes, some of them in genes involved in epigenetic patterning. In a previous study, we demonstrated global DNA methylation changes in CC, indicating major contribution of epigenetic alterations to cholangiocarcinogenesis. Here, we aimed at the identification and characterization of CC-related, differentially methylated regions (DMRs) in potential microRNA promoters and of genes targeted by identified microRNAs...
September 3, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Hazem E Hassan, Jean-Arnaud Keita, Lawrence Narayan, Sean M Brady, Richard Frederick, Samuel Carlson, Karen C Glass, Senthil Natesan, Thomm Buttolph, Tamer E Fandy
Curcumin and its analogs exhibited antileukemic activity either as single agent or in combination therapy. Dimethoxycurcumin (DMC) is a more metabolically stable curcumin analog that was shown to induce the expression of promoter-methylated genes without reversing DNA methylation. Accordingly, co-treatment with DMC and DNA methyltransferase (DNMT) inhibitors could hypothetically enhance the re-expression of promoter-methylated tumor suppressor genes. In this study, we investigated the cytotoxic effects and epigenetic changes associated with the combination of DMC and the DNMT inhibitor decitabine (DAC) in primary leukemia samples and cell lines...
September 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Jarrett D Morrow, Michael H Cho, Craig P Hersh, Victor Pinto-Plata, Bartolome Celli, Nathaniel Marchetti, Gerard Criner, Raphael Bueno, George Washko, Kimberly Glass, Augustine M K Choi, John Quackenbush, Edwin K Silverman, Dawn L DeMeo
Chronic obstructive pulmonary disease (COPD) is a smoking-related disease characterized by genetic and phenotypic heterogeneity. Although association studies have identified multiple genomic regions with replicated associations to COPD, genetic variation only partially explains the susceptibility to lung disease, and suggests the relevance of epigenetic investigations. We performed genome-wide DNA methylation profiling in homogenized lung tissue samples from 46 control subjects with normal lung function and 114 subjects with COPD, all former smokers...
August 26, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Omar Ali, Diana Cerjak, Jack W Kent, Roland James, John Blangero, Melanie A Carless, Yi Zhang
Epigenetic mechanisms, including DNA methylation, mediate the interaction between gene and environment and may play an important role in the obesity epidemic. We assessed the relationship between DNA methylation and obesity in peripheral blood mononuclear cells (PBMCs) at 485,000 CpG sites across the genome in family members (8-90 y of age) using a discovery cohort (192 individuals) and a validation cohort (1,052 individuals) of Northern European ancestry. After Bonferroni-correction (Pα=0.05 = 1.31 × 10(-7)) for genome-wide significance, we identified 3 loci, cg18181703 (SOCS3), cg04502490 (ZNF771), and cg02988947 (LIMD2), where methylation status was associated with body mass index percentile (BMI%), a clinical index for obesity in children, adolescents, and adults...
August 26, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Xinyu Zhang, Amy C Justice, Ying Hu, Zuoheng Wang, Hongyu Zhao, Guilin Wang, Eric O Johnson, Brinda Emu, Richard E Sutton, John H Krystal, Ke Xu
Epigenetic control of human immunodeficiency virus-1 (HIV-1) genes is critical for viral integration and latency. However, epigenetic changes in the HIV-1-infected host genome have not been well characterized. Here, we report the first large-scale epigenome-wide association study of DNA methylation for HIV-1 infection. We recruited HIV-infected (n = 261) and uninfected (n = 117) patients from the Veteran Aging Cohort Study (VACS) and all samples were profiled for 485,521 CpG sites in DNA extracted from the blood...
August 12, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Simone Jueliger, John Lyons, Sara Cannito, Illar Pata, Pille Pata, Marianna Shkolnaya, Oriana Lo Re, Marion Peyrou, Francesc Villarroya, Valerio Pazienza, Francesca Rappa, Francesco Cappello, Mohammad Azab, Pietro Taverna, Manlio Vinciguerra
Hepatocellular carcinoma (HCC) is a deadly malignancy characterized at the epigenetic level by global DNA hypomethylation and focal hypermethylation on the promoter of tumor suppressor genes. In most cases it develops on a background of liver steatohepatitis, fibrosis, and cirrhosis. Guadecitabine (SGI-110) is a second-generation hypomethylating agent, which inhibits DNA methyltransferases. Guadecitabine is formulated as a dinucleotide of decitabine and deoxyguanosine that is resistant to cytidine deaminase (CDA) degradation and results in prolonged in vivo exposure to decitabine following small volume subcutaneous administration of guadecitabine...
August 11, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Kevin A Hope, Mark S LeDoux, Lawrence T Reiter
In mammals, expression of UBE3A is epigenetically regulated in neurons and expression is restricted to the maternal copy of UBE3A. A recent report claimed that Drosophila melanogaster UBE3A homolog (Dube3a) is preferentially expressed from the maternal allele in fly brain, inferring an imprinting mechanism. However, complex epigenetic regulatory features of the mammalian imprinting center are not present in Drosophila, and allele specific expression of Dube3a has not been documented. We used behavioral and electrophysiological analysis of the Dube3a loss-of-function allele (Dube3a(15b)) to investigate Dube3a imprinting in fly neurons...
August 11, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Oskar Karlsson, Rodosthenis S Rodosthenous, Calvin Jara, Kasey J Brennan, Robert O Wright, Andrea A Baccarelli, Rosalind J Wright
Breastmilk has many documented beneficial effects on the developing human infant, but the components of breastmilk that influence these developmental pathways have not been fully elucidated. Increasing evidence suggests that non-coding RNAs encapsulated in extracellular vesicles (EVs) represent an important mechanism of communication between the mother and child. Long non-coding RNAs (lncRNAs) are of particular interest given their key role in gene expression and development. However, it is not known whether breastmilk EVs contain lncRNAs...
August 5, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Kristina Gervin, Christian Magnus Page, Hans Christian D Aass, Michelle A Jansen, Heidi Elisabeth Fjeldstad, Bettina Kulle Andreassen, Liesbeth Duijts, Joyce B van Meurs, Menno C van Zelm, Vincent W Jaddoe, Hedvig Nordeng, Gunn Peggy Knudsen, Per Magnus, Wenche Nystad, Anne Cathrine Staff, Janine F Felix, Robert Lyle
Epigenome-wide association studies of prenatal exposure to different environmental factors are becoming increasingly common. These studies are usually performed in umbilical cord blood. Since blood comprises multiple cell types with specific DNA methylation patterns, confounding caused by cellular heterogeneity is a major concern. This can be adjusted for using reference data consisting of DNA methylation signatures in cell types isolated from blood. However, the most commonly used reference data set is based on blood samples from adult males and is not representative of the cell type composition in neonatal cord blood...
September 2016: Epigenetics: Official Journal of the DNA Methylation Society
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August 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Alison G Paquette, E Andres Houseman, Benjamin B Green, Corina Lesseur, David A Armstrong, Barry Lester, Carmen J Marsit
The placenta regulates the in utero environment and functionally impacts fetal development. Candidate gene studies identified variation in placental DNA methylation is associated with newborn neurologic and behavioral outcomes including movement quality, lethargic behavior, attention, and arousal. We sought to identify novel regions of variable DNA methylation associated with newborn attention, lethargy, quality of movement, and arousal by performing an epigenome-wide association study in 335 infants from a US birth cohort...
August 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
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