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Epigenetic methylation signature

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https://www.readbyqxmd.com/read/28938489/prognostic-classifier-based-on-genome-wide-dna-methylation-profiling-in-well-differentiated-thyroid-tumors
#1
Mariana Bisarro Dos Reis, Mateus Camargo Barros-Filho, Fábio Albuquerque Marchi, Caroline Moraes Beltrami, Hellen Kuasne, Clóvis Antônio Lopes Pinto, Srikant Ambatipudi, Zdenko Herceg, Luiz Paulo Kowalski, Silvia Regina Rogatto
Context: Even though the majority of well-differentiated thyroid cancer (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidences have suggested that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis. Objective: To identify a prognostic epigenetic signature in thyroid cancer. Design: Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 non-neoplastic thyroid tissues (NT), 17 benign thyroid lesions (BTL) and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 Hürthle cell, 1 poorly differentiated and 3 anaplastic)...
August 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28935858/modular-fluorescence-complementation-sensors-for-live-cell-detection-of-epigenetic-signals-at-endogenous-genomic-sites
#2
Cristiana Lungu, Sabine Pinter, Julian Broche, Philipp Rathert, Albert Jeltsch
Investigation of the fundamental role of epigenetic processes requires methods for the locus-specific detection of epigenetic modifications in living cells. Here, we address this urgent demand by developing four modular fluorescence complementation-based epigenetic biosensors for live-cell microscopy applications. These tools combine engineered DNA-binding proteins with domains recognizing defined epigenetic marks, both fused to non-fluorescent fragments of a fluorescent protein. The presence of the epigenetic mark at the target DNA sequence leads to the reconstitution of a functional fluorophore...
September 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28933623/the-defining-dna-methylation-signature-of-kabuki-syndrome-enables-functional-assessment-of-genetic-variants-of-unknown-clinical-significance
#3
Erfan Aref-Eshghi, Laila C Schenkel, Hanxin Lin, Cindy Skinner, Peter Ainsworth, Guillaume Paré, David Rodenhiser, Charles Schwartz, Bekim Sadikovic
Kabuki syndrome (KS) is caused by mutations in KMT2D, which is a histone methyltransferase involved in methylation of H3K4, a histone marker associated with DNA methylation. Analysis of >450,000 CpGs in 24 KS patients with pathogenic mutations in KMT2D and 216 controls, identified several genomic regions, along with 1,504 CpG sites with significant DNA methylation changes including a number of Hox genes and the MYO1F gene. Using the most differentiating and significant probes and regions we developed a "methylation variant pathogenicity (MVP) score," which enables 100% sensitive and specific identification of individuals with KS, which was confirmed using multiple public and internal patient DNA methylation databases...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28927277/benchmark-dose-modeling-estimates-of-the-concentrations-of-inorganic-arsenic-that-induce-changes-to-the-neonatal-transcriptome-proteome-and-epigenome-in-a-pregnancy-cohort
#4
Julia Rager, Scott S Auerbach, Grace A Chappell, Elizabeth Martin, Chad Thompson, Rebecca C Fry
Prenatal inorganic arsenic (iAs) exposure influences the expression of critical genes and proteins associated with adverse outcomes in newborns, in part through epigenetic mediators. The doses at which these genomic and epigenomic changes occur have yet to be evaluated in the context of dose-response modeling. The goal of the present study was to estimate iAs doses that correspond to changes in transcriptomic, proteomic, epigenomic, and integrated multi-omic signatures in human cord blood through benchmark dose (BMD) modeling...
September 19, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28926430/targeting-histone-methylation-in-cancer
#5
Michael T McCabe, Helai P Mohammad, Olena Barbash, Ryan G Kruger
Most, if not all, human cancers exhibit altered epigenetic signatures that promote aberrant gene expression that contributes to cellular transformation. Historically, attempts to pharmacologically intervene in this process have focused on DNA methylation and histone acetylation. More recently, genome-wide studies have identified histone and chromatin regulators as one of the most frequently dysregulated functional classes in a wide range of cancer types. These findings have provided numerous potential therapeutic targets including many that affect histone methylation...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28925878/genistein-induces-alterations-of-epigenetic-modulatory-signatures-in-human-cervical-cancer-cells
#6
Madhumitha Kedhari Sundaram, Mohammad Zeeshan Ansari, Abdullah Al Mutery, Maryam Ashraf, Reem Nasab, Sheethal Rai, Naushad Rais, Arif Hussain
Introduction Epidemiological studies indicate that diet rich in fruits and vegetables are associated with decreased cancer risk thereby indicating that dietary polyphenols can be potential chemo-preventive agents. The reversible nature of epigenetic modifications makes them a favorable target for cancer prevention. Polyphenols have been shown to reverse aberrant epigenetic patterns by targeting the regulatory enzymes, DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). In vitro and in silico studies of DNMTs and HDACs were planned to examine genistein's role as a natural epigenetic modifier in human cervical cancer cells, HeLa...
September 18, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28915705/promising-landscape-for-regulating-macrophage-polarization-epigenetic-viewpoint
#7
REVIEW
Dexi Zhou, Kui Yang, Lu Chen, Wen Zhang, Zhenyu Xu, Jian Zuo, Hui Jiang, Jiajie Luan
Macrophages are critical myeloid cells with the hallmark of phenotypic heterogeneity and functional plasticity. Macrophages phenotypes are commonly described as classically-activated M1 and alternatively-activated M2 macrophages which play an essential role in the tissues homeostasis and diseases pathogenesis. Alternations of macrophage polarization and function states require precise regulation of target-gene expression. Emerging data demonstrate that epigenetic mechanisms and transcriptional factors are becoming increasingly appreciated in the orchestration of macrophage polarization in response to local environmental signals...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915634/dna-methylation-signature-of-long-noncoding-rna-genes-during-human-pre-implantation-embryonic-development
#8
Jingyu Li, Wei Han, Xiaoli Shen, Shubiao Han, Hong Ye, Guoning Huang
DNA methylation have crucial roles in regulating the expression of developmental genes during mammalian pre-implantation embryonic development (PED). However, the DNA methylation dynamic pattern of long noncoding RNA (lncRNA) genes, one type of epigenetic regulators, in human PED have not yet been demonstrated. Here, we performed a comprehensive analysis of lncRNA genes in human PED based on public reduced representation bisulphite sequencing (RRBS) data. We observed that both lncRNA and protein-coding genes complete the major demethylation wave at the 2-cell stage, whereas the promoters of lncRNA genes show higher methylation level than protein-coding genes during PED...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912427/dna-methylation-profiling-reveals-common-signatures-of-tumorigenesis-and-defines-epigenetic-prognostic-subtypes-of-canine-diffuse-large-b-cell-lymphoma
#9
Serena Ferraresso, Arianna Aricò, Tiziana Sanavia, Silvia Da Ros, Massimo Milan, Luciano Cascione, Stefano Comazzi, Valeria Martini, Mery Giantin, Barbara Di Camillo, Sandro Mazzariol, Diana Giannuzzi, Laura Marconato, Luca Aresu
Epigenetic deregulation is a hallmark of cancer characterized by frequent acquisition of new DNA methylation in CpG islands. To gain insight into the methylation changes of canine DLBCL, we investigated the DNA methylome in primary DLBCLs in comparison with control lymph nodes by genome-wide CpG microarray. We identified 1,194 target loci showing different methylation levels in tumors compared with controls. The hypermethylated CpG loci included promoter, 5'-UTRs, upstream and exonic regions. Interestingly, targets of polycomb repressive complex in stem cells were mostly affected suggesting that DLBCL shares a stem cell-like epigenetic pattern...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28898397/genome-wide-dna-methylation-analysis-of-senescence-in-repetitively-infected-memory-ctls-dna-methylation-analysis-of-repetitively-infected-memory-ctls
#10
Jumpei Shosaku
The immune system including antigen-specific CD8 T cells, which are cytotoxic T lymphocytes (CTLs), can acquire the potential of more effective elimination of the pathogen for reinfection. Since memory CTLs could exert protective immunity after the next response, we aimed to elucidate the substantial change of repetitively infected memory CTLs. Currently, DNA methylation status in repetitively infected memory CTLs is still unknown. Therefore, we performed next generation sequencing (NGS) to evaluate methylation status and transcriptional regulation of naive, primary and secondary memory CD8 T cells on the basis of transcription start sites (TSS)...
September 12, 2017: Immunology
https://www.readbyqxmd.com/read/28891455/epigenetic-biomarkers-for-risk-assessment-of-particulate-matter-associated-lung-cancer
#11
Arpit Bhargava, Neha Bunkar, Aniket Aglawe, Kailash Chand Pandey, Rajnarayan Tiwari, Koel Chaudhury, Irina Yu Goryacheva, Pradyumna Kumar Mishra
BACKGROUND: Particulate matter directly emitted into the air by sources such as combustion processes and windblown dust, or formed in the atmosphere by transformation of emitted gases are the major contributors to air pollution that triggers a diverse array of human pathologies including lung cancer. The mortality in lung cancer is usually high as the disease is not symptomatic at its early treatable stage. Moreover, available methods for screening are costly and mainly rely on imaging techniques which lack sufficient sensitivity and specificity...
September 10, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28889375/a-versatile-assay-for-detection-of-aberrant-dna-methylation-in-bladder-cancer
#12
Stella Tommasi, Ahmad Besaratinia
Urothelial carcinoma of the bladder is one of the most common malignancies in the industrialized world, mainly caused by smoking and occupational exposure to chemicals. The favorable prognosis of early stage bladder cancer underscores the importance of early detection for the treatment of this disease. The high recurrence rate of this malignancy also highlights the need for close post-diagnosis monitoring of bladder cancer patients. As for other malignancies, aberrant DNA methylation has been shown to play a crucial role in the initiation and progression of bladder cancer, and thus holds great promise as a diagnostic and prognostic biological marker...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28887637/epigenetic-regulation-in-cell-senescence
#13
REVIEW
Li-Qin Cheng, Zhu-Qin Zhang, Hou-Zao Chen, De-Pei Liu
Cell senescence, which is an irreversible state of cell proliferative arrest, has emerged as a potentially important contributor to tissue dysfunction and organismal ageing. Cell senescence is triggered by a variety of senescence stressors, which affect gene expression and multiple signalling pathways that give rise to various senescence phenotypes. Epigenetic mechanisms, as critical regulators of chromosomal architecture and gene expression, have added an extra dimension to the molecular mechanisms of cell senescence...
September 8, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28886103/epigenetic-regulation-of-human-sox3-gene-expression-during-early-phases-of-neural-differentiation-of-nt2-d1-cells
#14
Vladanka Topalovic, Aleksandar Krstic, Marija Schwirtlich, Diletta Dolfini, Roberto Mantovani, Milena Stevanovic, Marija Mojsin
Sox3/SOX3 is one of the earliest neural markers in vertebrates. Together with the Sox1/SOX1 and Sox2/SOX2 genes it is implicated in the regulation of stem cell identity. In the present study, we performed the first analysis of epigenetic mechanisms (DNA methylation and histone marks) involved in the regulation of the human SOX3 gene expression during RA-induced neural differentiation of NT2/D1 cells. We show that the promoter of the human SOX3 gene is extremely hypomethylated both in undifferentiated NT2/D1 cells and during the early phases of RA-induced neural differentiation...
2017: PloS One
https://www.readbyqxmd.com/read/28882489/folate-and-microrna-bidirectional-interactions
#15
REVIEW
Emma L Beckett, Martin Veysey, Mark Lucock
Low folate status is linked to increased risk of a number of conditions, including developmental disorders, some cancers, neurodegenerative and cardiovascular diseases. Some of the mechanisms of these associations are known, but much remains to be elucidated. Aberrant microRNA (miRNA) profiles are also signatures of these conditions, and as such, the association between folate status and miRNA are now being investigated. Potential associations are bidirectional, with miRNA linked to regulation of folate-mediated pathways, and folate linked to modulation of miRNA expression...
September 4, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28881822/an-epigenetic-signature-of-adhesion-molecules-predicts-poor-prognosis-of-ovarian-cancer-patients
#16
Ping-Ying Chang, Yu-Ping Liao, Hui-Chen Wang, Yu-Chih Chen, Rui-Lan Huang, Yu-Chi Wang, Chiou-Chung Yuan, Hung-Cheng Lai
DNA methylation is a promising biomarker for cancer. The epigenetic effects of cell adhesion molecules may affect the therapeutic outcome and the present study examined their effects on survival in ovarian cancer. We integrated methylomics and genomics datasets in The Cancer Genome Atlas (n = 391) and identified 106 highly methylated adhesion-related genes in ovarian cancer tissues. Univariate analysis revealed the methylation status of eight genes related to progression-free survival. In multivariate Cox regression analysis, four highly methylated genes (CD97, CTNNA1, DLC1, HAPLN2) and three genes (LAMA4, LPP, MFAP4) with low methylation were significantly associated with poor progression-free survival...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881789/pulmonary-endothelial-cell-dna-methylation-signature-in-pulmonary-arterial-hypertension
#17
Aurélie Hautefort, Julie Chesné, Jens Preussner, Soni S Pullamsetti, Jorg Tost, Mario Looso, Fabrice Antigny, Barbara Girerd, Marianne Riou, Saadia Eddahibi, Jean-François Deleuze, Werner Seeger, Elie Fadel, Gerald Simonneau, David Montani, Marc Humbert, Frédéric Perros
Pulmonary arterial hypertension (PAH) is a severe and incurable pulmonary vascular disease. One of the primary origins of PAH is pulmonary endothelial dysfunction leading to vasoconstriction, aberrant angiogenesis and smooth muscle cell proliferation, endothelial-to-mesenchymal transition, thrombosis and inflammation. Our objective was to study the epigenetic variations in pulmonary endothelial cells (PEC) through a specific pattern of DNA methylation. DNA was extracted from cultured PEC from idiopathic PAH (n = 11), heritable PAH (n = 10) and controls (n = 18)...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878180/bariatric-surgery-and-precision-nutrition
#18
REVIEW
Carolina F Nicoletti, Cristiana Cortes-Oliveira, Marcela A S Pinhel, Carla B Nonino
This review provides a literature overview of new findings relating nutritional genomics and bariatric surgery. It also describes the importance of nutritional genomics concepts in personalized bariatric management. It includes a discussion of the potential role bariatric surgery plays in altering the three pillars of nutritional genomics: nutrigenetics, nutrigenomics, and epigenetics. We present studies that show the effect of each patient's genetic and epigenetic variables on the response to surgical weight loss treatment...
September 6, 2017: Nutrients
https://www.readbyqxmd.com/read/28860502/bi-directional-and-shared-epigenomic-signatures-following-proton-and-56-fe-irradiation
#19
Soren Impey, Timothy Jopson, Carl Pelz, Amanuel Tafessu, Fatema Fareh, Damian Zuloaga, Tessa Marzulla, Lara-Kirstie Riparip, Blair Stewart, Susanna Rosi, Mitchell S Turker, Jacob Raber
The brain's response to radiation exposure is an important concern for patients undergoing cancer therapy and astronauts on long missions in deep space. We assessed whether this response is specific and prolonged and is linked to epigenetic mechanisms. We focused on the response of the hippocampus at early (2-weeks) and late (20-week) time points following whole body proton irradiation. We examined two forms of DNA methylation, cytosine methylation (5mC) and hydroxymethylation (5hmC). Impairments in object recognition, spatial memory retention, and network stability following proton irradiation were observed at the two-week time point and correlated with altered gene expression and 5hmC profiles that mapped to specific gene ontology pathways...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28860464/characterization-of-a-core-region-in-the-a2ucoe-that-confers-effective-anti-silencing-activity
#20
Fang Zhang, Giorgia Santilli, Adrian J Thrasher
We have previously shown that reliability of the A2UCOE in driving transgene expression can be attributed to its resistance to DNA methylation, and its ability to confer this property to linked regulatory sequences. In order to gain a better understanding of how resistance to DNA methylation from the A2UCOE is conferred, and whether the anti-silencing effect from the A2UCOE is confined within a core region, we evaluated the anti-silencing effect of different sub-domains. We found that maximal epigenetic regulatory activity was contained within a 455 bp element derived from the CBX3 region when tested in the context of a lentiviral vector in murine embryonic stem (ES) cells and human inducible pluripotent stem (iPS) cells...
August 31, 2017: Scientific Reports
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