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Epigenetics: Official Journal of the DNA Methylation Society

Christian Flotho
Juvenile myelomonocytic leukemia (JMML) stands out among malignant neoplasms of childhood in several ways. First, JMML is a model condition to elucidate the relevance of deregulated Ras signal transduction in human cancer. Second, the identification of Ras pathway mutations in JMML has informed the field of germline cancer predisposition and advanced the understanding of molecular mechanisms underlying the progression from predisposition to neoplasia. Third and not least, genomic DNA methylation was discovered to play a salient role in the classification and prognostication of the disease...
February 18, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Chantel L Martin, Dereje Jima, Gemma C Sharp, Lauren E McCullough, Sarah S Park, Kymberly M Gowdy, David Skaar, Michael Cowley, Rachel L Maguire, Bernard Fuemmeler, David Collier, Caroline L Relton, Susan K Murphy, Cathrine Hoyo
Pre-pregnancy obesity is an established risk factor for adverse sex-specific cardiometabolic health in offspring. Epigenetic alterations, such as in DNA methylation (DNAm), are a hypothesized link; however, sex-specific epigenomic targets remain unclear. Leveraging data from the Newborn Epigenetics Study (NEST) cohort, linear regression models were used to identify CpG sites in cord blood leukocytes associated with pre-pregnancy obesity in 187 mother-female and 173 mother-male offsprings. DNAm in cord blood was measured using the Illumina HumanMethylation450k BeadChip...
February 18, 2019: Epigenetics: Official Journal of the DNA Methylation Society
David John Hunter, Lynsey James, Bethan Hussey, Alex J Wadley, Martin R Lindley, Sarabjit S Mastana
Lifestyle interventions, including exercise and dietary supplementation, can modify DNA methylation and exert health benefits; however, the underlying mechanisms are poorly understood. Here we investigated the impact of acute aerobic exercise and the supplementation of omega-3 polyunsaturated fatty acids (n-3 PUFA) and extra virgin olive oil (EVOO) on global and gene-specific (PPARGC1A, IL6 and TNF) DNA methylation, and DNMT mRNA expression in leukocytes of disease-free individuals. Eight trained male cyclists completed an exercise test before and after a four-week supplementation of n-3 PUFA and EVOO in a double-blind, randomised, repeated measures design...
February 14, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Ashok Sharma, Mustafa Albahrani, Wa Zhang, Christina N Kufel, Smitha R James, Kunle Odunsi, David Klinkebiel, Adam R Karpf
The POTE gene family consists of 14 homologous genes localized to autosomal pericentromeres, and a sub-set of POTEs are cancer-testis antigen (CTA) genes. POTEs are over-expressed in epithelial ovarian cancer (EOC), including the high-grade serous subtype (HGSC), and expression of individual POTEs correlates with chemoresistance and reduced survival in HGSC. The mechanisms driving POTE overexpression in EOC and other cancers is unknown. Here, we investigated the role of epigenetics in regulating POTE expression, with a focus on DNA hypomethylation...
February 14, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Jiaxuan Liu, Wei Zhao, Farah Ammous, Stephen T Turner, Thomas H Mosley, Xiang Zhou, Jennifer A Smith
Changes in DNA methylation may be a potential mechanism that mediates the effects of smoking on physiological function and subsequent disease risk. Given the dynamic nature of the epigenome, longitudinal studies are indispensable for investigating smoking-induced methylation changes over time. Using blood samples collected approximately five years apart in 380 African Americans (mean age 60.7 years) from the Genetic Epidemiology Network of Arteriopathy (GENOA) study, we measured DNA methylation levels using Illumina HumanMethylation BeadChips...
February 14, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Kirk L West, Stephanie D Byrum, Samuel G Mackintosh, Rick D Edmondson, Sean D Taverna, Alan J Tackett
Arsenic exposure is a global health problem. Millions of people encounter arsenic through contaminated drinking water, consumption, and inhalation. The arsenic response locus in budding yeast is responsible for the detoxification of arsenic and its removal from the cell. This locus constitutes a conserved pathway ranging from prokaryotes to higher eukaryotes. The goal of this study was to identify how transcription from the arsenic response locus is regulated in an arsenic dependent manner. An affinity enrichment strategy called CRISPR-Chromatin Affinity Purification with Mass Spectrometry (CRISPR-ChAP-MS) was used, which provides for the proteomic characterization of a targeted locus...
February 10, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Eric Smith, Yoko Tomita, Helen M Palethorpe, Stuart Howell, Maryam Nakhjavani, Amanda R Townsend, Timothy J Price, Joanne P Young, Jennifer E Hardingham
Aquaporin-1 (AQP1) is a homo-tetrameric transmembrane protein that facilitates rapid movement of water and ions across cell membranes. The clinical significance of AQP1 expression in colorectal carcinoma (CRC) is controversial. The aim of this study was to investigate the prognostic significance of AQP1 transcript expression and the association between expression and promoter methylation in normal colonic mucosa, CRC tissues and cell lines. Analysis of publicly available datasets from The Cancer Genome Atlas revealed that AQP1 expression was significantly decreased in CRC compared to normal mucosa (12...
February 9, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Wubin Ding, Geng Chen, Tieliu Shi
DNA methylation status is closely associated with diverse diseases, and is generally more stable than gene expression, thus abnormal DNA methylation could be important biomarkers for tumor diagnosis, treatment and prognosis. However, the signatures regarding DNA methylation changes for pan-cancer diagnosis and prognosis are less explored. Here we systematically analyzed the genome-wide DNA methylation patterns in diverse TCGA cancers with machine learning. We identified seven CpG sites that could effectively discriminate tumor samples from adjacent normal tissue samples for 12 main cancers of TCGA (1216 samples, AUC > 0...
January 29, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Benjamin V Becker, Leonhard Kaatsch, Richard Obermair, Gerrit Schrock, Matthias Port, Reinhard Ullmann
DNA hydroxymethylation has gained attention as an intermediate in the process of DNA demethylation. More recently, 5-hydroxymethylcytosine has been recognized as an independent epigenetic mark that can persist over time and that exerts influence on gene regulation and other biological processes. Deregulation of this DNA modification has been linked to tumorigenesis and a variety of other diseases. The impact of irradiation on DNA hydroxymethylation is poorly understood. In this study we exposed lung fibroblasts (IMR90) to 0...
January 29, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Sarah W Curtis, Dawayland O Cobb, Varun Kilaru, Metrecia L Terrell, Elizabeth M Kennedy, M Elizabeth Marder, Dana Boyd Barr, Carmen J Marsit, Michele Marcus, Karen N Conneely, Alicia K Smith
In 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added to farm animal feed. Highly exposed individuals and their children have experienced endocrine-related health problems, though the underlying mechanism behind these remains unknown. We investigated whether PBB exposure is associated with variation in DNA methylation in peripheral blood samples from 658 participants of the Michigan PBB registry using the MethylationEPIC BeadChip, as well as investigated what the potential function of the affected regions are and whether these epigenetic marks are known to associate with endocrine system pathways...
January 24, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Ruyang Zhang, Linjing Lai, Jieyu He, Chao Chen, Dongfang You, Weiwei Duan, Xuesi Dong, Ying Zhu, Lijuan Lin, Sipeng Shen, Yichen Guo, Li Su, Andrea Shafer, Sebastian Moran, Thomas Fleischer, Maria Moksnes Bjaanæs, Anna Karlsson, Maria Planck, Johan Staaf, Åslaug Helland, Manel Esteller, Yongyue Wei, Feng Chen, David C Christiani
Hypoxia occurs frequently in human cancers and promotes stabilization and activation of hypoxia inducible factor (HIF). HIF-1α is specific for the hypoxia response, and its degradation mediated by three enzymes EGLN1, EGLN2 and EGLN3. Although EGLNs expression has been found to be related to prognosis of many cancers, few studies examined DNA methylation in EGLNs and its relationship to prognosis of early-stage non-small cell lung cancer (NSCLC). We analyzed EGLNs DNA methylation data from tumor tissue samples of 1,230 early-stage NSCLC patients from five international cohorts, as well as gene expression data from The Cancer Genome Atlas (TCGA)...
January 21, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Huili Wang, Erika E Paulson, Libing Ma, Pablo J Ross, Richard M Schultz
Enhancer of zeste homolog 2 (EZH2), a component of the PRC2 complex, trimethylates H3K27, a transcriptionally repressive histone mark. EZH2 is encoded by a dormant maternal mRNA and inhibiting the maturation-associated increase in EZH2 activity using either a combined siRNA/morpholino approach or a small molecule inhibitor (GSK343) inhibits development of diploidized parthenotes to the blastocyst stage but not inseminated eggs, with longer GSK343 treatments leading to progressively greater inhibition of development...
January 19, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Zhen Zeng, Jiayao Wu, Andriy Kovalchuk, Tommaso Raffaello, Zilan Wen, Mengxia Liu, Fred O Asiegbu
Heterobasidion parviporum is the most devastating fungal pathogen of conifer forests in Northern Europe. The fungus has dual life strategies, necrotrophy on living trees and saprotrophy on dead woods. DNA cytosine methylation is an important epigenetic modification in eukaryotic organisms. Our presumption is that the lifestyle transition and asexual development in H. parviporum could be driven by epigenetic effects. Involvements of DNA methylation in the regulation of aforementioned processes have never been studied thus far...
January 11, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Cecilia C Beyrne, Rodrigo M González, Norberto D Iusem
One common experimental hurdle that arises when explore patterns of cytosine methylation is the generation of data derived from a single specific tissue, often arduous to isolate from a heterogeneous biospecimen. Here we show a new strategy for exploring environment- or mutation-caused changes in cell type- or tissue-specific methylation landscapes, which requires neither transgenic reporter cell lines nor physical separation. This approach takes advantage of a known distinct methylation signature existing in only one of the tissues within an organ under a particular condition...
January 11, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Ainash Childebayeva, Tamara R Jones, Jaclyn M Goodrich, Fabiola Leon-Velarde, Maria Rivera-Chira, Melisa Kiyamu, Tom D Brutsaert, Dana C Dolinoy, Abigail W Bigham
Recent discoveries indicate a genetic basis for high-altitude adaptation among human groups who have resided at high altitude for millennia, including Andeans, Tibetans, and Ethiopians. Yet, genetics alone does not explain the extent of variation in altitude-adaptive phenotypes. Current and past environments may also play a role, and one way to determine the effect of the environment is through the epigenome. To characterize if Andean adaptive responses to high altitude have an epigenetic component, we analyzed DNA methylation of the promoter region of EPAS1 and LINE-1 repetitive element among 572 Quechua individuals from high- (4,388 m) and low-altitude (0 m) in Peru...
December 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Tamsyn M Uren Webster, Deiene Rodriguez-Barreto, Samuel A M Martin, Cock van Oosterhout, Pablo Orozco-terWengel, Joanne Cable, Alastair Hamilton, Carlos Garcia de Leaniz, Sofia Consuegra
Stress experienced during early life may have lasting effects on the immune system, with impacts on health and disease dependent on the nature and duration of the stressor. The epigenome is especially sensitive to environmental stimuli during early life and represents a potential mechanism through which stress may cause long-lasting health effects. However, the extent to which the epigenome responds differently to chronic vs acute stressors is unclear, especially for non-mammalian species. We examined the effects of acute stress (cold-shock during embryogenesis) and chronic stress (absence of tank enrichment during larval-stage) on global gene expression (using RNA-seq) and DNA methylation (using RRBS) in the gills of Atlantic salmon (Salmo salar) four months after hatching...
December 11, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Yue Wu, Karen E Peterson, Brisa N Sánchez, Dana C Dolinoy, Adriana Mercado-Garcia, Martha M Téllez-Rojo, Jaclyn M Goodrich
Puberty is a developmentally plastic phase. Variations in pubertal tempo have implications for the risk of later adult diseases. Influences on pubertal tempo have been widely discussed, but the underlying biological mechanisms remain unclear. Epigenetic modifications are known to regulate development processes; they could play an important role in affecting pubertal outcomes. We conducted a population-based analysis to investigate the association of peripubertal blood DNA methylation at LINE-1 and growth-related candidate genes with pubertal onset and progression in healthy adolescents...
December 9, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Susan K Murphy, Nilda Itchon-Ramos, Zachary Visco, Zhiqing Huang, Carole Grenier, Rose Schrott, Kelly Acharya, Marie-Helene Boudreau, Thomas M Price, Douglas J Raburn, David L Corcoran, Joseph E Lucas, John T Mitchell, F Joseph McClernon, Marty Cauley, Brandon J Hall, Edward D Levin, Scott H Kollins
Little is known about the reproductive effects of paternal cannabis exposure. We evaluated associations between cannabis or tetrahydrocannabinol (THC) exposure and altered DNA methylation in sperm from humans and rats, respectively. DNA methylation, measured by reduced representation bisulfite sequencing, differed in the sperm of human users from non-users by at least 10% at 3,979 CpG sites. Pathway analyses indicated Hippo Signaling and Pathways in Cancer as enriched with altered genes (Bonferroni p<0.02)...
December 6, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Santiago Herrera, Wilfred C de Vega, David Ashbrook, Suzanne D Vernon, Patrick O McGowan
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease of unknown etiology. Multiple studies point to disruptions in immune functioning in ME/CFS patients as well as specific genetic polymorphisms and alterations of the DNA methylome in lymphocytes. However, potential interactions between DNA methylation and genetic background in relation to ME/CFS have not been examined. In this study we explored this association by characterizing the epigenetic (~480 thousand CpG loci) and genetic (~4...
December 5, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Teena Kjb Gamage, William Schierding, Daniel Hurley, Peter Tsai, Jackie L Ludgate, Chandrakanth Bhoothpur, Lawrence W Chamley, Robert J Weeks, Erin C Macaulay, Joanna L James
The placenta is a vital fetal exchange organ connecting mother and baby. Specialised placental epithelial cells, called trophoblasts, are essential for adequate placental function. Trophoblasts transform the maternal vasculature to allow efficient blood flow to the placenta and facilitate adequate nutrient uptake. Placental development is in part regulated by epigenetic mechanisms. However, our understanding of how DNA methylation contributes to human trophoblast differentiation is limited. To better understand how genome-wide methylation differences affect trophoblast differentiation, reduced representation bisulfite sequencing (RRBS) was conducted on four matched sets of trophoblasts (a candidate human trophoblast stem cell population), cytotrophoblasts (an intermediate progenitor population) and extravillous trophoblasts (EVT, a terminally differentiated population) each isolated from the same first trimester placenta...
November 26, 2018: Epigenetics: Official Journal of the DNA Methylation Society
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