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Epigenetics profilling

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https://www.readbyqxmd.com/read/29792762/genetic-profiling-in-acute-myeloid-leukemia-a-path-to-predicting-treatment-outcome
#1
Giuseppe Visani, Federica Loscocco, Alessandro Isidori, Pier Paolo Piccaluga
Despite substantial progresses in acute myeloid leukemia (AML) diagnosis and treatment, at least half of patient will eventually die for the disease. In the last decades, the use of genetic and genomic approaches allowed the identification of patients with higher risk of recurrence after and/or resistance to CHT. However, though many novel drugs have been proposed and tested, only little clinical improvements have been made concerning the treatment of the so called 'high risk' patients. Areas covered: In this article, the authors, based on their own experience and the most updated literature, review the basic knowledge of AML prognostication and treatment prediction developed throughout genetic and genomic profiling, and focus on the use of gene expression profiling as a promising predictive tool...
May 24, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29791073/elevated-histone-h3-acetylation-is-associated-with-genes-involving-in-t-lymphocyte-activation-and-gada-production-in-patients-with-type-1-diabetes
#2
Yanfei Wang, Can Hou, Jonathan Wisler, Kanhaiya Singh, Chao Wu, Zhiguo Xie, Qianjin Lu, Zhiguang Zhou
AIM: Genetic and epigenetic mechanisms have been implicated in the pathogenesis of type 1 diabetes (T1D), and histone acetylation is an epigenetic modification pattern that activates gene transcription. However, the genome-wide histone H3 acetylation in newly onset T1D patients has been less described. Accordingly, we aimed to unveil the genome-wide promoter acetylation profile in CD4+ T lymphocytes from T1D patients, especially for those with glutamate decarboxylase antibody (GADA) positive...
May 23, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29790956/5-hydroxymethylcytosine-alterations-in-the-human-postmortem-brains-of-autism-spectrum-disorder
#3
Ying Cheng, Ziyi Li, Sasicha Manupipatpong, Li Lin, Xuekun Li, Tianlei Xu, Yong-Hui Jiang, Qiang Shu, Hao Wu, Peng Jin
Autism spectrum disorders (ASD) include a group of syndromes characterized by impaired language, social, and communication skills, in addition to restrictive behaviors or stereotypes. However, with a prevalence of 1.5% in developed countries and high comorbidity rates, no clear underlying mechanism that unifies the heterogeneous phenotypes of ASD exists. 5-hydroxymethylcytosine (5hmC) is highly enriched in the brain and recognized as an essential epigenetic mark in developmental and brain disorders. To explore the role of 5hmC in ASD, we used the genomic DNA isolated from the postmortem cerebellum of both ASD patients and age-matched controls to profile genome-wide distribution of 5hmC...
May 22, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29790754/epiprofile-2-0-a-computational-platform-for-processing-epi-proteomics-mass-spectrometry-data
#4
Zuo-Fei Yuan, Simone Sidoli, Dylan M Marchione, Johayra Simithy, Kevin A Janssen, Mary R Szurgot, Benjamin A Garcia
Epigenetics has become a fundamental scientific discipline with various implications for biology and medicine. Epigenetic marks, mostly DNA methylation and histone post-translational modifications (PTMs), play important roles in chromatin structure and function. Accurate quantification of these marks is an ongoing challenge due to the variety of modifications and their wide dynamic range of abundance. Here, we present EpiProfile 2.0, an extended version of our 2015 software (v1.0) for accurate quantification of histone peptides based on liquid chromatography - tandem mass spectrometry (LC-MS/MS) analysis...
May 23, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29787577/analysis-of-micrornas-in-familial-mediterranean-fever
#5
Gil Amarilyo, Nir Pillar, Ilan Ben-Zvi, Daphna Weissglas-Volkov, Jonatan Zalcman, Liora Harel, Avi Livneh, Noam Shomron
OBJECTIVES: Although Familial Mediterranean fever (FMF) is categorized as autosomal recessive, frequent exceptions to this model exist and therefore we aimed to search epigenetic modifications in this disease. METHODS: Ten M694V homozygous FMF patients (the most severe phenotype) were recruited for this study. Patients with inflammatory flare were excluded. Total RNA was extracted from peripheral blood, and microRNA expression profiled using NanoString nCounter technology...
2018: PloS One
https://www.readbyqxmd.com/read/29787262/discovery-of-novel-pazopanib-based-hdac-and-vegfr-dual-inhibitors-targeting-cancer-epigenetics-and-angiogenesis-simultaneously
#6
Jie Zang, Xuewu Liang, Yongxue Huang, Yuping Jia, Xiaoyang Li, Wenfang Xu, C James Chou, Yingjie Zhang
Herein a novel series of pazopanib hybrids as polypharmacological antitumor agents were developed based on the crosstalk between histone deacetylases (HDACs) and vascular endothelial growth factor (VEGF) pathway. Among them, one ortho-aminoanilide 6d and one hydroxamic acid 13f exhibited considerable total HDACs and VEGFR-2 inhibitory activities. The HDAC inhibitory activities endowed 6d and 13f with potent antiproliferative activities, which was not observed in the approved VEGFR inhibitor pazopanib. Compounds 6d and 13f possessed comparable HDAC isoform selectivity profiles to the clinical class I HDAC inhibitor MS-275 and the approved pan-HDAC inhibitor SAHA, respectively...
May 22, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29786565/modelling-non-alcoholic-fatty-liver-disease-in-human-hepatocyte-like-cells
#7
Marcus J Lyall, Jessy Cartier, John P Thomson, Kate Cameron, Jose Meseguer-Ripolles, Eoghan O'Duibhir, Dagmara Szkolnicka, Baltasar Lucendo Villarin, Yu Wang, Giovanny Rodriguez Blanco, Warwick B Dunn, Richard R Meehan, David C Hay, Amanda J Drake
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in developed countries. An in vitro NAFLD model would permit mechanistic studies and enable high-throughput therapeutic screening. While hepatic cancer-derived cell lines are a convenient, renewable resource, their genomic, epigenomic and functional alterations mean their utility in NAFLD modelling is unclear. Additionally, the epigenetic mark 5-hydroxymethylcytosine (5hmC), a cell lineage identifier, is rapidly lost during cell culture, alongside expression of the Ten-eleven-translocation ( TET ) methylcytosine dioxygenase enzymes, restricting meaningful epigenetic analysis...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29785028/the-reference-epigenome-and-regulatory-chromatin-landscape-of-chronic-lymphocytic-leukemia
#8
Renée Beekman, Vicente Chapaprieta, Núria Russiñol, Roser Vilarrasa-Blasi, Núria Verdaguer-Dot, Joost H A Martens, Martí Duran-Ferrer, Marta Kulis, François Serra, Biola M Javierre, Steven W Wingett, Guillem Clot, Ana C Queirós, Giancarlo Castellano, Julie Blanc, Marta Gut, Angelika Merkel, Simon Heath, Anna Vlasova, Sebastian Ullrich, Emilio Palumbo, Anna Enjuanes, David Martín-García, Sílvia Beà, Magda Pinyol, Marta Aymerich, Romina Royo, Montserrat Puiggros, David Torrents, Avik Datta, Ernesto Lowy, Myrto Kostadima, Maša Roller, Laura Clarke, Paul Flicek, Xabier Agirre, Felipe Prosper, Tycho Baumann, Julio Delgado, Armando López-Guillermo, Peter Fraser, Marie-Laure Yaspo, Roderic Guigó, Reiner Siebert, Marc A Martí-Renom, Xose S Puente, Carlos López-Otín, Ivo Gut, Hendrik G Stunnenberg, Elias Campo, Jose I Martin-Subero
Chronic lymphocytic leukemia (CLL) is a frequent hematological neoplasm in which underlying epigenetic alterations are only partially understood. Here, we analyze the reference epigenome of seven primary CLLs and the regulatory chromatin landscape of 107 primary cases in the context of normal B cell differentiation. We identify that the CLL chromatin landscape is largely influenced by distinct dynamics during normal B cell maturation. Beyond this, we define extensive catalogues of regulatory elements de novo reprogrammed in CLL as a whole and in its major clinico-biological subtypes classified by IGHV somatic hypermutation levels...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29784784/uncovering-universal-rules-governing-the-selectivity-of-the-archetypal-dna-glycosylase-tdg
#9
Thomas Dodd, Chunli Yan, Bradley R Kossmann, Kurt Martin, Ivaylo Ivanov
Thymine DNA glycosylase (TDG) is a pivotal enzyme with dual roles in both genome maintenance and epigenetic regulation. TDG is involved in cytosine demethylation at CpG sites in DNA. Here we have used molecular modeling to delineate the lesion search and DNA base interrogation mechanisms of TDG. First, we examined the capacity of TDG to interrogate not only DNA substrates with 5-carboxyl cytosine modifications but also G:T mismatches and nonmismatched (A:T) base pairs using classical and accelerated molecular dynamics...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29782530/histone-methylation-changes-are-required-for-life-cycle-progression-in-the-human-parasite-schistosoma-mansoni
#10
David Roquis, Aaron Taudt, Kathrin K Geyer, Gilda Padalino, Karl F Hoffmann, Nancy Holroyd, Matt Berriman, Benoît Aliaga, Cristian Chaparro, Christoph Grunau, Ronaldo de Carvalho Augusto
Epigenetic mechanisms and chromatin structure play an important role in development. Their impact is therefore expected to be strong in parasites with complex life cycles and multiple, strikingly different, developmental stages, i.e. developmental plasticity. Some studies have already described how the chromatin structure, through histone modifications, varies from a developmental stage to another in a few unicellular parasites. However, this, to our knowledge, has never been done before in multicellular metazoan parasites...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29781253/developmental-plasticity-in-reptiles-insights-from-temperature-dependent-gene-expression-in-wall-lizard-embryos
#11
Nathalie Feiner, Alfredo Rago, Geoffrey M While, Tobias Uller
Many features of the development of reptiles are affected by temperature, but very little is known about how incubation temperature affects gene expression. Here, we provide a detailed case study of gene expression profiles in common wall lizard (Podarcis muralis) embryos developing at stressfully low (15°C) versus benign (24°C) temperature. For maximum comparability between the two temperature regimes, we selected a precise developmental stage early in embryogenesis defined by the number of somites. We used a split-clutch design and lizards from four different populations to evaluate the robustness of temperature-responsive gene expression profiles...
May 20, 2018: Journal of Experimental Zoology. Part A, Ecological and Integrative Physiology
https://www.readbyqxmd.com/read/29775961/antioxidant-response-elements-discovery-classes-regulation-and-potential-applications
#12
REVIEW
Azhwar Raghunath, Kiruthika Sundarraj, Raju Nagarajan, Frank Arfuso, Jinsong Bian, Alan P Kumar, Gautam Sethi, Ekambaram Perumal
Exposure to antioxidants and xenobiotics triggers the expression of a myriad of genes encoding antioxidant proteins, detoxifying enzymes, and xenobiotic transporters to offer protection against oxidative stress. This articulated universal mechanism is regulated through the cis-acting elements in an array of Nrf2 target genes called antioxidant response elements (AREs), which play a critical role in redox homeostasis. Though the Keap1/Nrf2/ARE system involves many players, AREs hold the key in transcriptional regulation of cytoprotective genes...
May 7, 2018: Redox Biology
https://www.readbyqxmd.com/read/29775429/genome-wide-dna-methylation-profiles-of-porcine-ovaries-in-estrus-and-proestrus
#13
Xiaolong Zhou, Songbai Yang, Feifei Yan, Ke He, Ayong Zhao
DNA methylation is an important epigenetic modification involved in the estrous cycle and the regulation of reproduction. Here, we investigated the genome-wide profiles of DNA methylation in porcine proestrus and estrus ovaries using methylated DNA immunoprecipitation sequencing (MeDIP-seq). The results showed that DNA methylation was enriched in intergenic and intron regions. The methylation levels of coding regions were higher than those of the 5' and 3' flanking regions of genes. There were 4813 differentially methylated regions (DMRs) of CpG islands in the estrus vs...
May 18, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29774579/integrative-epigenetic-analysis-reveals-therapeutic-targets-to-the-dna-methyltransferase-inhibitor-sgi-110-in-hepatocellular-carcinoma
#14
Minmin Liu, Lian Zhang, Hongtao Li, Toshinori Hinoue, Wanding Zhou, Hitoshi Ohtani, Anthony El-Khoueiry, John Daniels, Casey O'Connell, Tanya B Dorff, Qianjin Lu, Daniel J Weisenberger, Gangning Liang
There is an urgent need for developing more effective therapies for hepatocellular carcinoma (HCC) because of its aggressiveness. Guadecitabine (SGI-110) is a second-generation DNA methyltransferase inhibitor (DNMTi) currently in clinical trials for HCC and shows greater stability and performance over first generation DNMTis. In order to identify potential therapeutic targets of SGI-110 for clinical trials, HCC cell lines (SNU398, HepG2 and SNU475) were used to evaluate effects of transient SGI-110 treatment by an integrative analysis of DNA methylation, nucleosome accessibility, gene expression profiles and its clinical relevance by comparisons to TCGA HCC clinical data...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29774113/ezh2-inhibitors-sensitize-myeloma-cell-lines-to-panobinostat-resulting-in-unique-combinatorial-transcriptomic-changes
#15
Taylor Harding, Jessica Swanson, Brian Van Ness
Multiple myeloma (MM) remains a largely incurable hematologic cancer due to an inability to broadly target inevitable drug-resistant relapse. Epigenetic abnormalities are abundantly present in multiple myeloma and have increasingly demonstrated critical roles for tumor development and relapse to standard therapies. Accumulating evidence suggests that the histone methyltransferase EZH2 is aberrantly active in MM. We tested the efficacy of EZH2 specific inhibitors in a large panel of human MM cell lines (HMCLs) and found that only a subset of HMCLs demonstrate single agent sensitivity despite ubiquitous global H3K27 demethylation...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774081/g9a-stimulates-crc-growth-by-inducing-p53-lys373-dimethylation-dependent-activation-of-plk1
#16
Jie Zhang, Yafang Wang, Yanyan Shen, Pengxing He, Jian Ding, Yi Chen
Rationale: G9a is genetically deregulated in various tumor types and is important for cell proliferation; however, the mechanism underlying G9a-induced carcinogenesis, especially in colorectal cancer (CRC), is unclear. Here, we investigated if G9a exerts oncogenic effects in CRC by increasing polo-like kinase 1 (Plk1) expression. Thus, we further characterized the detailed molecular mechanisms. Methods: The role of Plk1 in G9a aberrant CRC was determined by performing different in vitro and in vivo assays, including assessment of cell growth by performing cell viability assay and assessment of signaling transduction profiles by performing immunoblotting, in the cases of pharmacological inhibition or short RNA interference-mediated suppression of G9a...
2018: Theranostics
https://www.readbyqxmd.com/read/29771158/global-methylation-profiles-in-buccal-cells-of-long-term-smokers-and-moist-snuff-consumers
#17
Walter J Jessen, Michael F Borgerding, G L Prasad
PURPOSE: Alternations in gene methylation and other epigenetic changes regulate normal development as well as drive disease progression. The aim of this study is to investigate global methylation changes in the buccal cells of smokers and smokeless tobacco users. MATERIALS AND METHODS: Generally healthy adult male subjects were recruited into Smoker (SMK), Moist Snuff Consumer (MSC) and Non-Tobacco Consumer (NTC) cohorts (40 subjects/cohort) (ClinicalTrials.gov Identifier: NCT01923402)...
May 17, 2018: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/29768164/epigenomic-guided-mass-cytometry-profiling-reveals-disease-specific-features-of-exhausted-cd8-t-cells
#18
Bertram Bengsch, Takuya Ohtani, Omar Khan, Manu Setty, Sasikanth Manne, Shaun O'Brien, Pier Federico Gherardini, Ramin Sedaghat Herati, Alexander C Huang, Kyong-Mi Chang, Evan W Newell, Niels Bovenschen, Dana Pe'er, Steven M Albelda, E John Wherry
Exhausted CD8 T (Tex) cells are immunotherapy targets in chronic infection and cancer, but a comprehensive assessment of Tex cell diversity in human disease is lacking. Here, we developed a transcriptomic- and epigenetic-guided mass cytometry approach to define core exhaustion-specific genes and disease-induced changes in Tex cells in HIV and human cancer. Single-cell proteomic profiling identified 9 distinct Tex cell clusters using phenotypic, functional, transcription factor, and inhibitory receptor co-expression patterns...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29765031/comprehensive-epigenetic-landscape-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#19
Rizi Ai, Teresina Laragione, Deepa Hammaker, David L Boyle, Andre Wildberg, Keisuke Maeshima, Emanuele Palescandolo, Vinod Krishna, David Pocalyko, John W Whitaker, Yuchen Bai, Sunil Nagpal, Kurtis E Bachman, Richard I Ainsworth, Mengchi Wang, Bo Ding, Percio S Gulko, Wei Wang, Gary S Firestein
Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29764806/temporal-efficacy-of-a-sulforaphane-based-broccoli-sprout-diet-in-prevention-of-breast-cancer-through-modulation-of-epigenetic-mechanisms
#20
Yuanyuan Li, Phillip Buckhaults, Shizhao Li, Trygve O Tollefsbol
Breast cancer is the most common cancer and the second leading cause of cancer death among women. An important risk factor for breast cancer is individual genetic background which is initially generated early in human life; for example, during the processes of embryogenesis and fetal development in utero. Bioactive dietary components such as sulforaphane (SFN), an isothiocyanate from cruciferous vegetables including broccoli sprouts (BSp), cabbage and kale, has been shown to reduce the risk of developing many common cancers through regulation of epigenetic mechanisms...
May 15, 2018: Cancer Prevention Research
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