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https://www.readbyqxmd.com/read/29351903/integrative-genomic-analysis-predicts-causative-cis-regulatory-mechanisms-of-the-breast-cancer-associated-genetic-variant-rs4415084
#1
Yi Zhang, Mohith Manjunath, Shilu Zhang, Deborah Chasman, Sushmita Roy, Jun S Song
Previous genome-wide association studies (GWAS) have identified several common genetic variants that may significantly modulate cancer susceptibility. However, the precise molecular mechanisms behind these associations remain largely unknown; it is often not clear whether discovered variants are themselves functional or merely genetically linked to other functional variants. Here we provide an integrated method for identifying functional regulatory variants associated with cancer and their target genes by combining analyses of expression quantitative trait loci (eQTL), a modified version of allele-specific expression (ASE) that systematically utilizes haplotype information, transcription factor (TF) binding preference, and epigenetic information...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29350283/epigenetic-regulation-of-neuroblastoma-development
#2
REVIEW
Durinck Kaat, Speleman Frank
In recent years, technological advances have enabled a detailed landscaping of the epigenome and the mechanisms of epigenetic regulation that drive normal cell function, development and cancer. Rather than merely a structural entity to support genome compaction, we now look at chromatin as a very dynamic and essential constellation that is actively participating in the tight orchestration of transcriptional regulation as well as DNA replication and repair. The unique feature of chromatin flexibility enabling fast switches towards more or less restricted epigenetic cellular states is, not surprisingly, intimately connected to cancer development and treatment resistance, and the central role of epigenetic alterations in cancer is illustrated by the finding that up to 50% of all mutations across cancer entities affect proteins controlling the chromatin status...
January 19, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29348151/ahrr-hypomethylation-lung-function-lung-function-decline-and-respiratory-symptoms
#3
Jakob B Kodal, Camilla J Kobylecki, Signe Vedel-Krogh, Børge G Nordestgaard, Stig E Bojesen
Introduction: Epigenome wide association studies have shown a consistent association between smoking exposure and hypomethylation in the aryl hydrocarbon receptor repressor(AHRR) gene(cg05575921). We tested the hypothesis that AHRR hypomethylation is associated with low lung function, steeper lung function decline, and respiratory symptoms in the general population.Methods:AHRR methylation extent was measured in 9113 individuals from the 1991-1994 examination of the Copenhagen City Heart Study, using bisulfite treated leucocyte DNA...
January 18, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29345757/whole-genome-sequencing-analysis-for-cancer-genomics-and-precision-medicine
#4
REVIEW
Hidewaki Nakagawa, Masashi Fujita
Explosive advances of next-generation sequencer (NGS) and computational analyses have been exploring somatic protein-altered mutations in most cancer types and these coding mutation data are intensively accumulated. However, there is limited information on somatic mutations in non-coding regions including introns, regulatory elements, and non-coding RNAs, structural variants and pathogen in cancer genomes remain widely unexplored. Whole genome sequencing (WGS) approaches can comprehensively explore all types of genomic alterations in cancer and help us to better understand the whole landscape of driver mutations and mutational signature in cancer genomes and elucidate functional or clinical implications of these unexplored genomic regions and mutational signature...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29344884/analyzing-dna-methylation-patterns-during-tumor-evolution
#5
Heng Pan, Olivier Elemento
Epigenetic modifications play a key role in cellular development and tumorigenesis. Recent large-scale genomic studies have shown that mutations in players of the epigenetic machinery and concomitant perturbation of epigenomic patterning are frequent events in tumors. Among epigenetic marks, DNA methylation is one of the best studied. Hyper- and hypo-methylation events of specific regulatory elements (such as promoters and enhancers) are sometimes thought to be correlated with expression of nearby genes. High-throughput bisulfite converted sequencing is currently the technology of choice for studying DNA methylation in base-pair resolution and on whole-genome scale...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29344883/discovering-altered-regulation-and-signaling-through-network-based-integration-of-transcriptomic-epigenomic-and-proteomic-tumor-data
#6
Amanda J Kedaigle, Ernest Fraenkel
With the extraordinary rise in available biological data, biologists and clinicians need unbiased tools for data integration in order to reach accurate, succinct conclusions. Network biology provides one such method for high-throughput data integration, but comes with its own set of algorithmic problems and needed expertise. We provide a step-by-step guide for using Omics Integrator, a software package designed for the integration of transcriptomic, epigenomic, and proteomic data. Omics Integrator can be found at http://fraenkel...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29344347/epigenetic-alterations-in-tramp-mice-epigenome-dna-methylation-profiling-using-medip-seq
#7
Wenji Li, Ying Huang, Davit Sargsyan, Tin Oo Khor, Yue Guo, Limin Shu, Anne Yuqing Yang, Chengyue Zhang, Ximena Paredes-Gonzalez, Michael Verzi, Ronald P Hart, Ah-Ng Kong
Purpose: We investigated the genomic DNA methylation profile of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model and to analyze the crosstalk among targeted genes and the related functional pathways. Methods: Prostate DNA samples from 24-week-old TRAMP and C57BL/6 male mice were isolated. The DNA methylation profiles were analyzed by methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing (MeDIP-seq)...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29344313/dna-methylation-as-a-predictor-of-fetal-alcohol-spectrum-disorder
#8
Alexandre A Lussier, Alexander M Morin, Julia L MacIsaac, Jenny Salmon, Joanne Weinberg, James N Reynolds, Paul Pavlidis, Albert E Chudley, Michael S Kobor
Background: Fetal alcohol spectrum disorder (FASD) is a developmental disorder that manifests through a range of cognitive, adaptive, physiological, and neurobiological deficits resulting from prenatal alcohol exposure. Although the North American prevalence is currently estimated at 2-5%, FASD has proven difficult to identify in the absence of the overt physical features characteristic of fetal alcohol syndrome. As interventions may have the greatest impact at an early age, accurate biomarkers are needed to identify children at risk for FASD...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29343101/macon-a-web-tool-for-computing-dna-methylation-data-obtained-by-the-illumina-infinium-human-dna-methylation-beadarray
#9
Naoko Iida, Yoshihiro Okuda, Osamu Ogasawara, Satoshi Yamashita, Hideyuki Takeshima, Toshikazu Ushijima
AIM: Bioinformatics analysis for Illumina Infinium Human DNA methylation BeadArray is essential, but still remains difficult task for many experimental researchers. We here aimed to develop a browser-accessible bioinformatics tool for analyzing the BeadArray data. MATERIALS & METHODS: The tool was established as an analytical pipeline using R, Perl and Python programming languages. RESULTS: We introduced a method that groups neighboring probes into a genomic block, which facilitated efficient identification of densely methylated/unmethylated regions...
January 18, 2018: Epigenomics
https://www.readbyqxmd.com/read/29343074/understanding-the-influence-of-antipsychotic-drugs-on-global-methylation-events-and-its-relevance-in-treatment-response
#10
Babu Swathy, Koramannil R Saradalekshmi, Indu V Nair, Chandrasekharan Nair, Moinak Banerjee
AIM: The present study intends to evaluate whether antipsychotic drugs can modulate the host epigenome and if so whether drug-induced epigenetic modulation can explain the heterogeneity in drug response. METHODS: Present study was conducted in in vitro cells and significance of these in vitro observations was further evaluated in a clinical setting, between drug responsive and nonresponsive schizophrenia patients. A number of DNA modifications were assessed at global level using 5-methylcytosine, 5-hydroxymethylcytosine and 5-formylcytosine followed by evaluating the expression of epigenetic modifier genes and their crosstalk with miRNAs...
January 18, 2018: Epigenomics
https://www.readbyqxmd.com/read/29342232/informational-and-linguistic-analysis-of-large-genomic-sequence-collections-via-efficient-hadoop-cluster-algorithms
#11
Umberto Ferraro Petrillo, Gianluca Roscigno, Giuseppe Cattaneo, Raffaele Giancarlo
Motivation: Information theoretic and compositional/linguistic analysis of genomes have a central role in bioinformatics, even more so since the associated methodologies are becoming very valuable also for epigenomic and meta-genomic studies. The kernel of those methods is based on the collection of k-mer statistics, i.e., how many times each k-mer in {A;C; G; T}k occurs in a DNA sequence. Although this problem is computationally very simple and efficiently solvable on a conventional computer, the sheer amount of data available now in applications demands to resort to parallel and distributed computing...
January 12, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29342231/mapping-gene-regulatory-networks-from-single-cell-omics-data
#12
Mark W E J Fiers, Liesbeth Minnoye, Sara Aibar, Carmen Bravo González-Blas, Zeynep Kalender Atak, Stein Aerts
Single-cell techniques are advancing rapidly and are yielding unprecedented insight into cellular heterogeneity. Mapping the gene regulatory networks (GRNs) underlying cell states provides attractive opportunities to mechanistically understand this heterogeneity. In this review, we discuss recently emerging methods to map GRNs from single-cell transcriptomics data, tackling the challenge of increased noise levels and data sparsity compared with bulk data, alongside increasing data volumes. Next, we discuss how new techniques for single-cell epigenomics, such as single-cell ATAC-seq and single-cell DNA methylation profiling, can be used to decipher gene regulatory programmes...
January 12, 2018: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/29340017/altered-gnas-imprinting-due-to-folic-acid-deficiency-contributes-to-poor-embryo-development-and-may-lead-to-neural-tube-defects
#13
Li Wang, Shaoyan Chang, Zhen Wang, Shan Wang, Junsheng Huo, Gangqiang Ding, Rui Li, Chi Liu, Shaofang Shangguan, Xiaolin Lu, Ting Zhang, Zhiyong Qiu, Jianxin Wu
Disturbed epigenetic modifications have been linked to the pathogenesis of Neural Tube Defects (NTDs) in those with folate deficiency during pregnancy. However, evidence is lacking to delineate the critical region in epigenome regulated by parental folic acid and mechanisms by which folate deficiency affects normal embryogenesis. Our data from clinical samples revealed the presence of aberrant DNA methylation in GNAS imprinting cluster in NTD samples with low folate concentrations. Results from mouse models indicated that the establishment of GNAS imprinting was influenced by both maternal and paternal folate-deficient diets...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339976/detection-of-dioxin-induced-demethylation-of-mouse-cyp1a1-gene-promoter-by-a-new-labeling-method-for-short-dna-fragments-possessing-5-methylcytosine-at-the-end
#14
Hisaka Kurita, Toshiki Aiba, Toshiyuki Saito, Seiichiroh Ohsako
Environmental factors stimulate alteration of DNA methylation level. Investigation of the genome-wide DNA methylation status is important for environmental health studies. We here designed a genomic DNA amplification and labeling protocol using a methylation-sensitive restriction enzyme HinP1 I. This method can specifically amplify genomic DNA fragments possessing methyl-CpG at the end. The fragments are a relatively short size and dominantly located on CpG-islands. By using the samples prepared by this method, a dioxin-induced change in the methylation level of the mouse Cyp1a1 promoter was successfully evaluated using oligonucleotide probes covalently bound onto a glass plate...
2018: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/29339533/learning-dependent-chromatin-remodeling-highlights-noncoding-regulatory-regions-linked-to-autism
#15
John N Koberstein, Shane G Poplawski, Mathieu E Wimmer, Giulia Porcari, Charlly Kao, Bruce Gomes, Davide Risso, Hakon Hakonarson, Nancy R Zhang, Robert T Schultz, Ted Abel, Lucia Peixoto
Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder that is associated with genetic risk factors. Most human disease-associated single-nucleotide polymorphisms (SNPs) are not located in genes but rather are in regulatory regions that control gene expression. The function of regulatory regions is determined through epigenetic mechanisms. Parallels between the cellular basis of development and the formation of long-term memory have long been recognized, particularly the role of epigenetic mechanisms in both processes...
January 16, 2018: Science Signaling
https://www.readbyqxmd.com/read/29339507/large-scale-comparative-epigenomics-reveals-hierarchical-regulation-of-non-cg-methylation-in-arabidopsis
#16
Yu Zhang, C Jake Harris, Qikun Liu, Wanlu Liu, Israel Ausin, Yanping Long, Lidan Xiao, Li Feng, Xu Chen, Yubin Xie, Xinyuan Chen, Lingyu Zhan, Suhua Feng, Jingyi Jessica Li, Haifeng Wang, Jixian Zhai, Steven E Jacobsen
Genome-wide characterization by next-generation sequencing has greatly improved our understanding of the landscape of epigenetic modifications. Since 2008, whole-genome bisulfite sequencing (WGBS) has become the gold standard for DNA methylation analysis, and a tremendous amount of WGBS data has been generated by the research community. However, the systematic comparison of DNA methylation profiles to identify regulatory mechanisms has yet to be fully explored. Here we reprocessed the raw data of over 500 publicly available Arabidopsis WGBS libraries from various mutant backgrounds, tissue types, and stress treatments and also filtered them based on sequencing depth and efficiency of bisulfite conversion...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339137/oxygen-induced-alterations-in-the-expression-of-chromatin-modifying-enzymes-and-the-transcriptional-regulation-of-imprinted-genes
#17
William M Skiles, Avery Kester, Jane H Pryor, Mark E Westhusin, Michael C Golding, Charles R Long
Embryo culture and assisted reproductive technologies have been associated with a disproportionately high number of epigenetic abnormalities in the resulting offspring. However, the mechanisms by which these techniques influence the epigenome remain poorly defined. In this study, we evaluated the capacity of oxygen concentration to influence the transcriptional control of a selection of key enzymes regulating chromatin structure. In mouse embryonic stem cells, oxygen concentrations modulated the transcriptional regulation of the TET family of enzymes, as well as the de novo methyltransferase Dnmt3a...
January 12, 2018: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/29334780/rules-governing-the-mechanism-of-epigenetic-reprogramming-memory
#18
Phuc-Loi Luu, Daniela Gerovska, Hans R Schöler, Marcos J Araúzo-Bravo
AIM: Disclosing the mechanisms that regulate reprogramming memory. MATERIALS & METHODS: We established computational procedure to find DNA methylation somatic memory sites (SMSs) at single CpGs and integrated them with genomics, epigenomics, transcriptomics and imprinting information. RESULTS & CONCLUSION: Reprogramming memory persists at late passages in low methylated regions. Contrarily to hypomethylated, hypermethylated SMSs occur at evolutionary conserved sites overlapping active transcription loci in dynamic chromatin regions...
January 16, 2018: Epigenomics
https://www.readbyqxmd.com/read/29334376/positively-selected-enhancer-elements-endow-osteosarcoma-cells-with-metastatic-competence
#19
James J Morrow, Ian Bayles, Alister P W Funnell, Tyler E Miller, Alina Saiakhova, Michael M Lizardo, Cynthia F Bartels, Maaike Y Kapteijn, Stevephen Hung, Arnulfo Mendoza, Gursimran Dhillon, Daniel R Chee, Jay T Myers, Frederick Allen, Marco Gambarotti, Alberto Righi, Analisa DiFeo, Brian P Rubin, Alex Y Huang, Paul S Meltzer, Lee J Helman, Piero Picci, Henri Versteeg, John Stamatoyannopolus, Chand Khanna, Peter C Scacheri
Metastasis results from a complex set of traits acquired by tumor cells, distinct from those necessary for tumorigenesis. Here, we investigate the contribution of enhancer elements to the metastatic phenotype of osteosarcoma. Through epigenomic profiling, we identify substantial differences in enhancer activity between primary and metastatic human tumors and between near isogenic pairs of highly lung metastatic and nonmetastatic osteosarcoma cell lines. We term these regions metastatic variant enhancer loci (Met-VELs)...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29333921/targeting-brd4-proteins-suppresses-the-growth-of-nsclc-through-downregulation-of-eif4e-expression
#20
Zhongyuan Gao, Ting Yuan, Xiao Zhou, Ping Ni, Geng Sun, Ping Li, Zhixiang Cheng, Xuerong Wang
Lung cancer is the leading cause of cancer-related death worldwide. Bromodomain and extraterminal domain (BET) proteins act as epigenome readers for gene transcriptional regulation. Among BET family members, BRD4 was well studied, but for its mechanism in non-small cell lung carcinoma has not been elucidated. eIF4E regulates gene translation and has been proved to play an important role in the progression of lung cancer. In this study, we first confirmed that BET inhibitors JQ1 and I-BET151 suppressed the growth of NSCLCs, in parallel with downregulated eIF4E expression...
January 15, 2018: Cancer Biology & Therapy
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