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Epigenetics: Official Journal of the DNA Methylation Society

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https://www.readbyqxmd.com/read/28080202/chemical-probes-targeting-epigenetic-proteins-applications-beyond-oncology
#1
Suzanne Ackloo, Peter J Brown, Susanne Müller
Epigenetic chemical probes are potent, cell-active, small molecule inhibitors and antagonists of specific domains in a protein; they have been indispensable for studying bromodomains and protein methyltransferases. The Structural Genomics Consortium (SGC), comprising scientists from academic and pharmaceutical laboratories, has generated most of the current epigenetic chemical probes. Moreover, the SGC has shared about four thousand aliquots of these probes, which have been used primarily for phenotypic profiling or to validate targets in cell lines or primary patient samples cultured in vitro...
January 12, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28075199/an-epigenome-wide-association-analysis-of-cardiac-autonomic-responses-among-a-population-of-welders
#2
Jinming Zhang, Zhonghua Liu, Peter E Umukoro, Jennifer M Cavallari, Shona C Fang, Marc G Weisskopf, Xihong Lin, Murray A Mittleman, David C Christiani
DNA methylation is one of the potential epigenetic mechanisms associated with various adverse cardiovascular effects; however, its association with cardiac autonomic dysfunction, in particular, is unknown. In the current study, we aimed to identify epigenetic variants associated with alterations in cardiac autonomic responses. Cardiac autonomic responses were measured with two novel markers: acceleration capacity (AC) and deceleration capacity (DC). We examined DNA methylation levels at more than 472,506 CpG probes through the Illumina Infinium HumanMethylation450 BeadChip assay...
January 11, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28071961/cellular-analysis-of-the-action-of-epigenetics-drugs-and-probes
#3
Mirjam Hau, Fides Zenk, A Ganesan, Nicola Iovino, Manfred Jung
Small molecule drugs and probes are important tools in drug discovery, pharmacology, and cell biology. This is of course also true for epigenetic inhibitors. Important examples for the use of established epigenetic inhibitors are the study of the mechanistic role of a certain target in a cellular setting or the modulation of a certain phenotype in an approach that aims towards therapeutic application. Alternatively, cellular testing may aim at the validation of a new epigenetic inhibitor in drug discovery approaches...
January 10, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28059605/fetal-dna-hypermethylation-in-tight-junction-pathway-is-associated-with-neural-tube-defects-a-genome-wide-dna-methylation-analysis
#4
Linlin Wang, Shanshan Lin, Ji Zhang, Tian Tian, Lei Jin, Aiguo Ren
Neural tube defects (NTDs) are a spectrum of severe congenital malformations of fusion failure of the neural tube during early embryogenesis. Evidence on aberrant DNA methylation in NTD development remains scarce, especially when exposure to environmental pollutant is taken into consideration. DNA methylation profiling was quantified using the Infinium HumanMethylation450 array in neural tissues from 10 NTD cases and 8 non-malformed controls (stage 1). Subsequent validation was performed using a Sequenom MassARRAY system in neural tissues from 20 NTD cases and 20 non-malformed controls (stage 2)...
January 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28059604/valentin-haecker-1864-1927-as-a-pioneer-of-phenogenetics-building-the-bridge-between-genotype-and-phenotype
#5
Uwe Hoßfeld, Elizabeth Watts, Georgy S Levit
Valentin Haecker is one of the forerunners of experimental biology, genetics, and developmental physiology. Haecker introduced the term Phänogenetik (phenogenetics) in 1918 in Entwicklungsgeschichtliche Eigenschaftsanalyse (Evolutionary Analysis of Characters), in which he described the earliest stages in the development of the phenotype. (1) His major objective in this publication was to integrate the two most important concepts of Mendelian genetics-phenotype and genotype-within a well-articulated theory...
January 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28059593/clinical-relevance-of-epigenetics-in-the-onset-and-management-of-type-2-diabetes-mellitus
#6
Linda Sommese, Alberto Zullo, Francesco Paolo Mancini, Rossella Fabbricini, Andrea Soricelli, Claudio Napoli
Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling β-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects...
January 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28059592/mutual-regulation-of-micrornas-and-dna-methylation-in-human-cancers
#7
Sumei Wang, Wanyin Wu, Francois X Claret
microRNAs (miRNAs) and DNA methylation are the two epigenetic modifications that have emerged in recent years as the most critical players in the regulation of gene expression. Compelling evidence has indicated the roles of miRNAs and DNA methylation in modulating cellular transformation and tumorigenesis. miRNAs act as negative regulators of gene expression and are involved in the regulation of both physiological conditions and during diseases, such as cancer, inflammatory diseases, and psychiatric disorders, among others...
January 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28059591/epigenetic-modification-in-chromatin-machinery-and-its-deregulation-in-pediatric-brain-tumors-insight-into-epigenetic-therapies
#8
Eleonore Maury, Rintaro Hashizume
Malignancies are characterized by the reprogramming of epigenetic patterns. This reprogramming includes gains or losses in DNA methylation and disruption of normal patterns of covalent histone modifications, which are associated with changes in chromatin remodeling processes. This review will focus on the mechanisms underlying this reprogramming and, specifically, on the role of histone modification in chromatin machinery and the modifications in epigenetic processes occurring in brain cancer, with a specific focus on epigenetic therapies for pediatric brain tumors...
January 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28059589/an-hp1-isoform-specific-feedback-mechanism-regulates-suv39h1-activity-under-stress-conditions
#9
Helena Raurell-Vila, Laia Bosch-Presegue, Jessica Gonzalez, Noriko Kane-Goldsmith, Carmen Casal, Jeremy P Brown, Anna Marazuela-Duque, Prim B Singh, Lourdes Serrano, Alejandro Vaquero
The presence of H3K9me3 and heterochromatin protein 1 (HP1) are hallmarks of heterochromatin conserved in eukaryotes. The spreading and maintenance of H3K9me3 is effected by the functional interplay between the H3K9me3-specific histone methyltransferase Suv39h1 and HP1. This interplay is complex in mammals because the three HP1 isoforms, HP1α, β, and γ, are thought to play a redundant role in Suv39h1-dependent deposition of H3K9me3 in pericentric heterochromatin (PCH). Here, we demonstrate that despite this redundancy, HP1α and, to a lesser extent, HP1γ have a closer functional link to Suv39h1, compared to HP1β...
January 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28059585/initiation-of-aberrant-dna-methylation-patterns-and-heterogeneity-in-precancerous-lesions-of-human-hepatocellular-cancer
#10
Ryan A Hlady, Dan Zhou, William Puszyk, Lewis R Roberts, Chen Liu, Keith D Robertson
While intratumor heterogeneity contributes to disease progression, metastasis, and resistance to chemotherapy, it also provides a route to understanding the evolution and drivers of disease. Defects in epigenetic landscapes are intimately linked to pathogenesis of a variety of human diseases, with epigenetic deregulation promoting tumorigenesis. Understanding epigenetic heterogeneity is crucial in hepatocellular carcinoma (HCC), where epigenetic alterations are frequent, early, and pathogenic events. We determined genome-wide DNA methylation and copy number variation leveraging the Infinium 450 K in a series of regenerative nodules from within single patient livers...
January 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28055307/a-comparison-of-existing-global-dna-methylation-assays-to-low-coverage-whole-genome-bisulfite-sequencing-for-epidemiological-studies
#11
Florence K Crary-Dooley, Mitchell E Tam, Keith W Dunaway, Irva Hertz-Picciotto, Rebecca J Schmidt, Janine M LaSalle
DNA methylation is an epigenetic mark at the interface of genetic and environmental factors relevant to human disease. Quantitative assessments of global DNA methylation levels have therefore become important tools in epidemiology research, particularly for understanding effects of environmental exposures in complex diseases. Among the available methods of quantitative DNA methylation measurements, bisulfite sequencing is considered the gold standard, but whole-genome bisulfite sequencing (WGBS) has previously been considered too costly for epidemiology studies with high sample numbers...
January 5, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28055298/vitamin-d-limits-inflammation-linked-microrna-expression-in-adipocytes-in-vitro-and-in-vivo-a-new-mechanism-for-the-regulation-of-inflammation-by-vitamin-d
#12
Esma Karkeni, Lauriane Bonnet, Julie Marcotorchino, Franck Tourniaire, Julien Astier, Jianping Ye, Jean-François Landrier
Inflammation of adipose tissue is believed to be a contributing factor to many chronic diseases associated with obesity. Vitamin D (VD) is now known to limit this metabolic inflammation by decreasing inflammatory marker expression and leukocyte infiltration in adipose tissue. In this study, we investigated the impact of VD on microRNA (miR) expression in inflammatory conditions in human and mouse adipocytes, using high-throughput methodology (miRNA PCR arrays). Firstly, we identified three miRs (miR-146a, miR-150, and miR-155) positively regulated by TNFα in human adipocytes...
January 5, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28001461/tobacco-smoking-and-smoking-related-dna-methylation-are-associated-with-the-development-of-frailty-among-older-adults
#13
Xu Gao, Yan Zhang, Kai-Uwe Saum, Ben Schöttker, Lutz Philipp Breitling, Hermann Brenner
Tobacco smoking is a preventable environmental factor that contributes to a wide spectrum of age-related health outcomes; however, its association with the development of frailty is not yet well established. We examined the associations of self-reported smoking indicators, serum cotinine levels and smoking-related DNA methylation biomarkers with a quantitative frailty index (FI) in two independent subsets of older adults (age 50-75) recruited in Saarland, Germany in 2000 - 2002 (discovery set: n = 978, validation set: n = 531)...
December 21, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27982729/differential-dna-methylation-and-pm2-5-species-in-a-450k-epigenome-wide-association-study
#14
Lingzhen Dai, Amar Mehta, Irina Mordukhovich, Allan C Just, Jincheng Shen, Lifang Hou, Petros Koutrakis, David Sparrow, Pantel S Vokonas, Andrea A Baccarelli, Joel D Schwartz
Although there is growing evidence that exposure to ambient particulate matter is associated with global DNA methylation and gene-specific methylation, little is known regarding epigenome-wide changes in DNA methylation in relation to particles and, especially, particle components. Using the Illumina Infinium HumanMethylation450 BeadChip, we examined the relationship between one-year moving averages of PM2.5 species (Al, Ca, Cu, Fe, K, Na, Ni, S, Si, V, and Zn) and DNA methylation at 484,613 CpG probes in a longitudinal cohort that included 646 subjects...
December 16, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27982725/differential-analysis-of-genome-wide-methylation-and-gene-expression-in-mesenchymal-stem-cells-of-patients-with-fractures-and-osteoarthritis
#15
Alvaro Del Real, Flor M Pérez-Campo, Agustín F Fernández, Carolina Sañudo, Carmen G Ibarbia, María I Pérez-Núñez, Wim Van Criekinge, Maarten Braspenning, María A Alonso, Mario F Fraga, Jose A Riancho
Insufficient activity of the bone-forming osteoblasts leads to low bone mass and predisposes to fragility fractures. The functional capacity of mesenchymal stem cells (hMSCs), the precursors of osteoblasts, may be compromised in elderly individuals, in relation with the epigenetic changes associated with aging. However, the role of hMSCs in the pathogenesis of osteoporosis is still unclear. Therefore, we aimed to characterize the genome-wide methylation and gene expression signatures and the differentiation capacity of hMSCs from patients with hip fractures...
December 16, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27935420/the-epigenetic-regulation-of-dicer-and-microrna-biogenesis-by-panobinostat
#16
Nicholas C Hoffend, William J Magner, Thomas B Tomasi
microRNAs (miRs) are small noncoding RNAs that regulate/fine tune many cellular protein networks by targeting mRNAs for either degradation or translational inhibition. Dicer, a type III endoribonuclease, is a critical component in miR biogenesis and is required for mature mRNA production. Abnormal Dicer expression occurs in numerous cancer types and correlates with poor patient prognosis. Recent reports have demonstrated that epigenetic agents, including histone deacetylase inhibitors (HDACi), may regulate Dicer and miR expression...
December 9, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27935410/establishment-of-a-high-throughput-detection-system-for-dna-demethylating-agents
#17
Eriko Okochi-Takada, Naoko Hattori, Akihiro Ito, Tohru Niwa, Mika Wakabayashi, Kana Kimura, Minoru Yoshida, Toshikazu Ushijima
Epigenetic alterations underlie various human disorders, including cancer, and this has resulted in the development of drugs targeting epigenetic alterations. Although DNA demethylating agents are one of the major epigenetic drugs, only two compounds-5-azacytidine (5-aza-CR, azacitidine) and 5-aza-2'-deoxycytidine (5-aza-dC, decitabine)-have obtained clinical approval. Here, we aimed to establish a detection system for DNA demethylating agents suitable for a high-throughput screening (HTS) in mammalian cells...
December 9, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27918237/gpx3-promoter-methylation-predicts-platinum-sensitivity-in-colorectal-cancer
#18
Lorraine Pelosof, Sashidhar Yerram, Todd Armstrong, Nina Chu, Ludmila Danilova, Breann Yanagisawa, Manuel Hidalgo, Nilofer Azad, James G Herman
Epigenetic control of gene expression is a major determinant of tumor phenotype and has been found to influence sensitivity to individual chemotherapeutic agents. Glutathione peroxidase 3 (GPX3, plasma glutathione peroxidase) is a key component of cellular antioxidant regulation and its gene has been reported to be methylated in specific tumor types. GPX3 role in oxidative damage has been associated with sensitivity to platinums in other tumors but its importance in colorectal cancer (CRC) has not been determined...
December 5, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27918235/comprehensive-mapping-of-5-hydroxymethylcytosine-epigenetic-dynamics-in-axon-regeneration
#19
Yong-Hwee Eddie Loh, Andrew Koemeter-Cox, Mattéa Finelli, Li Shen, Roland H Friedel, Hongyan Zou
In contrast to central nervous system neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated in DRG neurons, along with increased 5-hydroxymethylcytosine (5 hmC). We generated genome-wide 5 hmC maps in adult DRG, which revealed that peripheral and central axotomy (leading to no regenerative effect) triggered differential 5 hmC changes that are associated with distinct signaling pathways...
December 5, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27911668/association-of-5-hydroxymethylation-and-5-methylation-of-dna-cytosine-with-tissue-specific-gene-expression
#20
V K Chaithanya Ponnaluri, Kenneth C Ehrlich, Guoqiang Zhang, Michelle Lacey, Douglas Johnston, Sriharsa Pradhan, Melanie Ehrlich
Differentially methylated or hydroxymethylated regions (DMRs) in mammalian DNA are often associated with tissue-specific gene expression but the functional relationships are still being unraveled. To elucidate these relationships, we studied 16 human genes containing myogenic DMRs by analyzing profiles of their epigenetics and transcription and quantitatively assaying 5-hydroxymethylcytosine (5 hmC) and 5-methylcytosine (5 mC) at specific sites in these genes in skeletal muscle (SkM), myoblasts, heart, brain, and diverse other samples...
December 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
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