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Epigenetic methylation signature

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https://www.readbyqxmd.com/read/28644958/translating-cancer-epigenomics-into-the-clinic-focus-on-lung-cancer
#1
REVIEW
Josep Mari-Alexandre, Angel Diaz-Lagares, Maria Villalba, Oscar Juan, Ana B Crujeiras, Alfonso Calvo, Juan Sandoval
Epigenetic deregulation is increasingly being recognized as a hallmark of cancer. Recent studies have identified many new epigenetic biomarkers, some of which are being introduced into clinical practice for diagnosis, molecular classification, prognosis or prediction of response to therapies. O-6-methylguanine-DNA methyltransferase gene is the most clinically advanced epigenetic biomarker as it predicts the response to temozolomide and carmustine in gliomas. Therefore, epigenomics may represent a novel and promising tool for precision medicine, and in particular, the detection of epigenomic biomarkers in liquid biopsies will be of great interest for monitoring diseases in patients...
June 2, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28637314/dna-methylation-signatures-and-coagulation-factors-in-the-peripheral-blood-leucocytes-of-epithelial-ovarian-cancer
#2
Lian Li, Hong Zheng, Yubei Huang, Caiyun Huang, Shuang Zhang, Jing Tian, Pei Li, Anil K Sood, Wei Zhang, Kexin Chen
Solid tumors are increasingly recognized as a systemic disease that is manifested by changes in DNA, RNA, proteins, and metabolites in the blood. Whereas many studies have reported gene mutation events in the circulation, few studies have focused on epigenetic DNA methylation markers. To identify DNA methylation biomarkers in peripheral blood for ovarian cancer, we performed a two-stage epigenome-wide association study. In the discovery stage, we measured genome wide DNA methylation for 485,000 CpG sites in peripheral blood in 24 epithelial ovarian cancer cases and 24 age-matched healthy controls...
June 16, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28630300/g9a-drives-hypoxia-mediated-gene-repression-for-breast-cancer-cell-survival-and-tumorigenesis
#3
Francesco Casciello, Fares Al-Ejeh, Greg Kelly, Donal J Brennan, Shin Foong Ngiow, Arabella Young, Thomas Stoll, Karolina Windloch, Michelle M Hill, Mark J Smyth, Frank Gannon, Jason S Lee
G9a is an epigenetic regulator that methylates H3K9, generally causing repression of gene expression, and participates in diverse cellular functions. G9a is genetically deregulated in a variety of tumor types and can silence tumor suppressor genes and, therefore, is important for carcinogenesis. Although hypoxia is recognized to be an adverse factor in tumor growth and metastasis, the role of G9a in regulating gene expression in hypoxia has not been described extensively. Here, we show that G9a protein stability is increased in hypoxia via reduced proline hydroxylation and, hence, inefficient degradation by the proteasome...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28615266/antitumor-effects-of-epidrug-ifnalpha%C3%A2-combination-driven-by-modulated-gene-signatures-in-both-colorectal-cancer-and-dendritic-cells
#4
Alessandra Fragale, Giulia Romagnoli, Valerio Licursi, Maria Buoncervello, Giorgia Del Vecchio, Caterina Giuliani, Stefania Parlato, Celeste Leone, Marta De Angelis, Irene Canini, Elena Toschi, Filippo Belardelli, Rodolfo Negri, Imerio Capone, Carlo Presutti, Lucia Gabriele
Colorectal cancer (CRC) results from progressive accumulation of genetic and epigenetic alterations. IFN signaling defects play an important role in the carcinogenesis process, in which the inability of IFN transcription regulatory factors (IRFs) to access regulatory sequences in IFN-stimulated genes (ISGs) in tumors and in immune cells may be pivotal. We reported that low-dose combination of two FDA-approved epidrugs, azacytidine (A) and romidepsin (R), with IFNa2 (ARI) hampers the aggressiveness of both CRC metastatic and stem cells in vivo and triggers immunogenic cell death signals that stimulate dendritic cell (DC) function...
June 14, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28604677/pramel7-mediates-ground-state-pluripotency-through-proteasomal-epigenetic-combined-pathways
#5
Urs Graf, Elisa A Casanova, Sarah Wyck, Damian Dalcher, Marco Gatti, Eva Vollenweider, Michal J Okoniewski, Fabienne A Weber, Sameera S Patel, Marc W Schmid, Jiwen Li, Jafar Sharif, Guido A Wanner, Haruhiko Koseki, Jiemin Wong, Pawel Pelczar, Lorenza Penengo, Raffaella Santoro, Paolo Cinelli
Naive pluripotency is established in preimplantation epiblast. Embryonic stem cells (ESCs) represent the immortalization of naive pluripotency. 2i culture has optimized this state, leading to a gene signature and DNA hypomethylation closely comparable to preimplantation epiblast, the developmental ground state. Here we show that Pramel7 (PRAME-like 7), a protein highly expressed in the inner cell mass (ICM) but expressed at low levels in ESCs, targets for proteasomal degradation UHRF1, a key factor for DNA methylation maintenance...
June 12, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28599291/dna-methylation-signature-of-long-noncoding-rna-genes-during-human-pre-implantation-embryonic-development
#6
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...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28575352/dna-methylation-signatures-in-cord-blood-of-icsi-children
#7
Nady El Hajj, Larissa Haertle, Marcus Dittrich, Sarah Denk, Harald Lehnen, Thomas Hahn, Martin Schorsch, Thomas Haaf
STUDY QUESTION: Does ICSI induce specific DNA methylation changes in the resulting offspring? SUMMARY ANSWER: Although several thousand analyzed CpG sites (throughout the genome) displayed significant between-group methylation differences, both ICSI and spontaneously conceived children varied within the normal range of methylation variation. WHAT IS KNOWN ALREADY: Children conceived by ART have increased risks for medical problems at birth and to the extent of present knowledge also in later life (i...
May 31, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28572541/pulmonary-endothelial-cell-dna-methylation-signature-in-pulmonary-arterial-hypertension
#8
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)...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28558752/epigenomic-and-functional-analyses-reveal-roles-of-epialleles-in-the-loss-of-photoperiod-sensitivity-during-domestication-of-allotetraploid-cottons
#9
Qingxin Song, Tianzhen Zhang, David M Stelly, Z Jeffrey Chen
BACKGROUND: Polyploidy is a pervasive evolutionary feature of all flowering plants and some animals, leading to genetic and epigenetic changes that affect gene expression and morphology. DNA methylation changes can produce meiotically stable epialleles, which are transmissible through selection and breeding. However, the relationship between DNA methylation and polyploid plant domestication remains elusive. RESULTS: We report comprehensive epigenomic and functional analyses, including ~12 million differentially methylated cytosines in domesticated allotetraploid cottons and their tetraploid and diploid relatives...
May 31, 2017: Genome Biology
https://www.readbyqxmd.com/read/28549776/methylome-and-transcriptome-profiling-in-myasthenia-gravis-monozygotic-twins
#10
Shimrat Mamrut, Nili Avidan, Frédérique Truffault, Elsebeth Staun-Ram, Tarek Sharshar, Bruno Eymard, Mélinée Frenkian, Jiri Pitha, Marc de Baets, Laurent Servais, Sonia Berrih-Aknin, Ariel Miller
OBJECTIVE: To identify novel genetic and epigenetic factors associated with Myasthenia gravis (MG) using an identical twins experimental study design. METHODS: The transcriptome and methylome of peripheral monocytes were compared between monozygotic (MZ) twins discordant and concordant for MG, as well as with MG singletons and healthy controls, all females. Sets of differentially expressed genes and differentially methylated CpGs were validated using RT-PCR for expression and target bisulfite sequencing for methylation on additional samples...
May 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28545587/type-2-diabetes-and-obesity-induce-similar-transcriptional-reprogramming-in-human-myocytes
#11
Leif Väremo, Tora Ida Henriksen, Camilla Scheele, Christa Broholm, Maria Pedersen, Mathias Uhlén, Bente Klarlund Pedersen, Jens Nielsen
BACKGROUND: Skeletal muscle is one of the primary tissues involved in the development of type 2 diabetes (T2D). The close association between obesity and T2D makes it difficult to isolate specific effects attributed to the disease alone. Therefore, here we set out to identify and characterize intrinsic properties of myocytes, associated independently with T2D or obesity. METHODS: We generated and analyzed RNA-seq data from primary differentiated myotubes from 24 human subjects, using a factorial design (healthy/T2D and non-obese/obese), to determine the influence of each specific factor on genome-wide transcription...
May 25, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28542303/differential-dna-methylation-of-msi2-and-its-correlation-with-diabetic-traits
#12
Jae-Pil Jeon, In-Uk Koh, Nak-Hyun Choi, Bong-Jo Kim, Bok-Ghee Han, Suman Lee
Differential DNA methylation with hyperglycemia is significantly associated with Type 2 Diabetes (T2D). Longtime extended exposure to high blood glucose levels can affect the epigenetic signatures in all organs. However, the relevance of the differential DNA methylation changes with hyperglycemia in blood with pancreatic islets remains unclear. We investigated differential DNA methylation in relation to glucose homeostasis based on the Oral Glucose Tolerance Test (OGTT) in a population-based cohort. We found a total of 382 differential methylation sites from blood DNA in hyperglycemia and type 2 diabetes subgroups using a longitudinal and cross-sectional approach...
2017: PloS One
https://www.readbyqxmd.com/read/28539478/a-novel-epigenetic-aml1-eto-thap10-mir-383-mini-circuitry-contributes-to-t-8-21-leukaemogenesis
#13
Yonghui Li, Qiaoyang Ning, Jinlong Shi, Yang Chen, Mengmeng Jiang, Li Gao, Wenrong Huang, Yu Jing, Sai Huang, Anqi Liu, Zhirui Hu, Daihong Liu, Lili Wang, Clara Nervi, Yun Dai, Michael Q Zhang, Li Yu
DNA methylation patterns are frequently deregulated in t(8;21) acute myeloid leukaemia (AML), but little is known of the mechanisms by which specific gene sets become aberrantly methylated. Here, we found that the promoter DNA methylation signature of t(8;21)(+) AML blasts differs from that of t(8;21)(-) AMLs. This study demonstrated that a novel hypermethylated zinc finger-containing protein, THAP10, is a target gene and can be epigenetically suppressed by AML1-ETO at the transcriptional level in t(8;21) AML...
May 24, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28528960/prenatal-stress-and-epigenetics
#14
REVIEW
L Cao-Lei, S R De Rooij, S King, S G Matthews, G A S Metz, T J Roseboom, M Szyf
In utero exposure to environmental stress in both animals and humans could result in long-term epigenome alterations and which further lead to consequences for adaptation and development in the offspring. Epigenetics, especially DNA methylation, is considered one of the most widely studied and well-characterized mechanisms involved in the long-lasting effects of in utero stress exposure. In this review, we outlined evidence from animal and human prenatal research supporting the view that prenatal stress could lead to lasting, broad and functionally organized signatures in DNA methylation which, in turn, could mediate exposure-phenotype associations...
May 18, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28516305/arsenic-toxicity-and-epimutagenecity-the-new-lineage
#15
REVIEW
Somnath Paul, Pritha Bhattacharjee, Ashok K Giri, Pritha Bhattacharjee
Global methylation pattern regulates the normal functioning of a cell. Research have shown arsenic alter these methylation landscapes within the genome leading to aberrant gene expression and inducts various pathophysiological outcomes. Long interspersed nuclear elements (LINE-1) normally remains inert due to heavy methylation of it's promoters, time and various environmental insults, they lose these methylation signatures and begin retro-transposition that has been associated with genomic instability and cancerous outcomes...
May 17, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28512252/epigenetic-regulation-of-zbtb18-promotes-glioblastoma-progression
#16
Vita Fedele, Fangping Dai, Anie Masilamani, Dieter Henrik Heiland, Eva Kling, Ana Gätjens-Sanchez, Roberto Ferrarese, Leonardo Platania, Soroush Doostkam, Hyunsoo Kim, Sven Nelander, Astrid Weyerbrock, Marco Prinz, Andrea Califano, Antonio Iavarone, Markus Bredel, Maria Stella Carro
Glioblastoma (GBM) is comprised of distinct subtypes characterized by their molecular profile. Mesenchymal identity in GBM has been associated with a comparatively unfavorable prognosis, primarily due to inherent resistance of these tumors to current therapies. The identification of molecular determinants of mesenchymal transformation could potentially allow for the discovery of new therapeutic targets. Zinc Finger and BTB Domain Containing 18 (ZBTB18/ZNF238/RP58) is a zinc finger transcriptional repressor with a crucial role in brain development and neuronal differentiation...
May 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28475860/charge-and-kabuki-syndromes-gene-specific-dna-methylation-signatures-identify-epigenetic-mechanisms-linking-these-clinically-overlapping-conditions
#17
Darci T Butcher, Cheryl Cytrynbaum, Andrei L Turinsky, Michelle T Siu, Michal Inbar-Feigenberg, Roberto Mendoza-Londono, David Chitayat, Susan Walker, Jerry Machado, Oana Caluseriu, Lucie Dupuis, Daria Grafodatskaya, William Reardon, Brigitte Gilbert-Dussardier, Alain Verloes, Frederic Bilan, Jeff M Milunsky, Raveen Basran, Blake Papsin, Tracy L Stockley, Stephen W Scherer, Sanaa Choufani, Michael Brudno, Rosanna Weksberg
Epigenetic dysregulation has emerged as a recurring mechanism in the etiology of neurodevelopmental disorders. Two such disorders, CHARGE and Kabuki syndromes, result from loss of function mutations in chromodomain helicase DNA-binding protein 7 (CHD7(LOF)) and lysine (K) methyltransferase 2D (KMT2D(LOF)), respectively. Although these two syndromes are clinically distinct, there is significant phenotypic overlap. We therefore expected that epigenetically driven developmental pathways regulated by CHD7 and KMT2D would overlap and that DNA methylation (DNAm) alterations downstream of the mutations in these genes would identify common target genes, elucidating a mechanistic link between these two conditions, as well as specific target genes for each disorder...
May 4, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28470479/epigenetic-variability-in-systemic-lupus-erythematosus-what-we-learned-from-genome-wide-dna-methylation-studies
#18
REVIEW
Maria Teruel, Amr H Sawalha
PURPOSE OF REVIEW: DNA methylation has emerged as an important contributing factor in the pathogenesis of systemic lupus erythematosus (SLE). Here, we describe the DNA methylation patterns identified in SLE and how these epigenetic changes can influence disease susceptibility, clinical heterogeneity, and disease flares. RECENT FINDINGS: Several genome-wide DNA methylation studies have been recently completed in SLE. Important observations include robust demethylation of interferon-regulated genes, which is consistent across all cell types studied to date, and is independent of disease activity...
June 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28459195/impact-of-viral-and-host-dna-methylations-on-hpv16-related-cervical-cancer-pathogenesis
#19
Shrinka Sen, Paramita Mandal, Amrapali Bhattacharya, Sudip Kundu, Rahul Roy Chowdhury, Nidhu Ranjan Mondal, Tanmay Chatterjee, Biman Chakravarty, Sudipta Roy, Sharmila Sengupta
Epigenetic alterations within human papillomavirus (HPV) and host cellular genomes are known to occur during cervical carcinogenesis. Our objective was to analyse the influence of (1) methylation within two immunostimulatory CpG motifs within HPV16 E6 and E7 genes around the viral late promoter and their correlation, if any, with expression deregulation of host receptor (TLR9) and DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) and (2) global DNA methylation levels within CpGs of the repetitive Alu sequences, on cervical cancer (CaCx) pathogenesis...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28455986/promising-landscape-for-regulating-macrophage-polarization-epigenetic-viewpoint
#20
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...
April 11, 2017: Oncotarget
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