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Epigenomics

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https://www.readbyqxmd.com/read/29474526/iwtomics-testing-high-resolution-sequence-based-omics-data-at-multiple-locations-and-scales
#1
Marzia A Cremona, Alessia Pini, Fabio Cumbo, Kateryna D Makova, Francesca Chiaromonte, Simone Vantini
Summary: With increased generation of high-resolution sequence-based "Omics" data, detecting statistically significant effects at different genomic locations and scales has become key to addressing several scientific questions. IWTomics is an R/Bioconductor package (integrated in Galaxy) that, exploiting sophisticated Functional Data Analysis techniques (i.e. statistical techniques that deal with the analysis of curves), allows users to pre-process, visualize and test these data at multiple locations and scales...
February 20, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29473816/dna-methylation-signatures-of-pulmonary-arterial-smooth-muscle-cells-in-chronic-thromboembolic-pulmonary-hypertension
#2
Ying Wang, Xiaoxi Huang, Dong Leng, Jifeng Li, Lei Wang, Yan Liang, Jun Wang, Ran Miao, Tao Jiang
Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease which is often underpinned by vascular remodeling. Although pulmonary arterial smooth muscle cells (PASMCs) are the main participants in vascular remodeling, their biological role in CTEPH is not entirely clear. In this study, we analyzed the whole epigenome-wide DNA methylation profiles of cultured PASMCs from CTEPH and control cell lines using an Illumina HumanMethylation450K BeadChip. A total of 6829 significantly differentially methylated probes (DMPs) were detected between the two groups, of which 4246 DMPs were hypermethylated while 2583 DMPs were hypomethylated...
February 23, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29473500/crispr-cas-system-as-a-genome-engineering-platform-applications-in-biomedicine-and-biotechnology
#3
Atieh Hashemi
Genome editing mediated by clustered regularly interspaced palindromic repeats (CRISPR) and its associated proteins (Cas) has recently been considered to be used as efficient, rapid and site-specific tools in the modification of endogenous genes in biomedically important cell types and whole organisms. It has become a predictable and precise method of choice for genome engineering by specifying a 20-nt targeting sequence within its guide RNA. First, this review aims to describe the biology of CRISPR system...
February 20, 2018: Current Gene Therapy
https://www.readbyqxmd.com/read/29472610/scnmt-seq-enables-joint-profiling-of-chromatin-accessibility-dna-methylation-and-transcription-in-single-cells
#4
Stephen J Clark, Ricard Argelaguet, Chantriolnt-Andreas Kapourani, Thomas M Stubbs, Heather J Lee, Celia Alda-Catalinas, Felix Krueger, Guido Sanguinetti, Gavin Kelsey, John C Marioni, Oliver Stegle, Wolf Reik
Parallel single-cell sequencing protocols represent powerful methods for investigating regulatory relationships, including epigenome-transcriptome interactions. Here, we report a single-cell method for parallel chromatin accessibility, DNA methylation and transcriptome profiling. scNMT-seq (single-cell nucleosome, methylation and transcription sequencing) uses a GpC methyltransferase to label open chromatin followed by bisulfite and RNA sequencing. We validate scNMT-seq by applying it to differentiating mouse embryonic stem cells, finding links between all three molecular layers and revealing dynamic coupling between epigenomic layers during differentiation...
February 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29471503/the-role-of-the-reprogramming-method-and-pluripotency-state-in-gamete-differentiation-from-patient-specific-human-pluripotent-stem-cells
#5
S Mishra, E Kacin, P Stamatiadis, S Franck, M Van der Jeught, H Mertes, G Pennings, P De Sutter, K Sermon, B Heindryckx, M Geens
The derivation of gametes from patient-specific pluripotent stem cells may provide new perspectives for genetic parenthood for patients currently facing sterility. We use current data to assess the gamete differentiation potential of patient-specific pluripotent stem cells and to determine which reprogramming strategy holds the greatest promise for future clinical applications. First, we compare the two best established somatic cell reprogramming strategies: the production of induced pluripotent stem cells (iPSC) and somatic cell nuclear transfer followed by embryonic stem cell derivation (SCNT-ESC)...
February 19, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29471014/epigenomic-drugs-and-the-germline-collateral-damage-in-the-home-of-heritability
#6
REVIEW
Patrick S Western
The testis and ovary provide specialised environments that nurture germ cells and facilitate their maturation, culminating in the production of mature gametes that can found the following generation. The sperm and egg not only transmit genetic information, but also epigenetic modifications that affect the development and physiology of offspring. Importantly, the epigenetic information contained in mature sperm and oocytes can be influenced by a range of environmental factors, such as diet, chemicals and drugs...
February 19, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29467772/genetic-and-genomic-tools-to-asssist-sugar-beet-improvement-the-value-of-the-crop-wild-relatives
#7
Filipa Monteiro, Lothar Frese, Sílvia Castro, Maria C Duarte, Octávio S Paulo, João Loureiro, Maria M Romeiras
Sugar beet ( Beta vulgaris L. ssp. vulgaris ) is one of the most important European crops for both food and sugar production. Crop improvement has been developed to enhance productivity, sugar content or other breeder's desirable traits. The introgression of traits from Crop Wild Relatives (CWR) has been done essentially for lessening biotic stresses constraints, namely using Beta and Patellifolia species which exhibit disease resistance characteristics. Several studies have addressed crop-to-wild gene flow, yet, for breeding programs genetic variability associated with agronomically important traits remains unexplored regarding abiotic factors...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29466355/epigenome-comparisons-reveal-linkage-between-gene-expression-and-postnatal-remodeling-of-chromatin-domain-topology
#8
Bruce H Howard, Tazuko H Hirai, Valya R Russanova
Substantial evidence has accumulated linking epigenome change to alterations in stem cell function during postnatal development and aging. Yet much remains to be learned about causal relationships, and large gaps remain in our understanding of epigenome-transcriptome interactions. Here we investigate structural features of large histone H3K27me3-enriched regions in human stem cell-like monocytes and their dendritic cell derivatives, where the H3K27me3 modification is considered to demarcate Polycomb (PcG) domains...
2018: PloS One
https://www.readbyqxmd.com/read/29466246/modified-aging-of-elite-athletes-revealed-by-analysis-of-epigenetic-age-markers
#9
Magdalena Spólnicka, Ewelina Pośpiech, Jakub Grzegorz Adamczyk, Ana Freire-Aradas, Beata Pepłońska, Renata Zbieć-Piekarska, Żanetta Makowska, Anna Pięta, Maria Victoria Lareu, Christopher Phillips, Rafał Płoski, Cezary Żekanowski, Wojciech Branicki
Recent progress in epigenomics has led to the development of prediction systems that enable accurate age estimation from DNA methylation data. Our objective was to track responses to intense physical exercise of individual age-correlated DNA methylation markers and to infer their potential impact on the aging processes. The study showed accelerated DNA hypermethylation for two CpG sites in TRIM59 and KLF14 . Both markers predicted the investigated elite athletes to be several years older than controls and this effect was more substantial in subjects involved in power sports...
February 15, 2018: Aging
https://www.readbyqxmd.com/read/29464059/characterization-and-metabolic-synthetic-lethal-testing-in-a-new-model-of-sdh-loss-familial-pheochromocytoma-and-paraganglioma
#10
John Smestad, Oksana Hamidi, Lin Wang, Molly Nelson Holte, Fatimah Al Khazal, Luke Erber, Yue Chen, L James Maher
Succinate dehydrogenase (SDH)-loss pheochromocytoma and paraganglioma (PPGL) are tumors driven by metabolic derangement. SDH loss leads to accumulation of intracellular succinate, which competitively inhibits dioxygenase enzymes, causing activation of pseudohypoxic signaling and hypermethylation of histones and DNA. The mechanisms by which these alterations lead to tumorigenesis are unclear, however. In an effort to fundamentally understand how SDH loss reprograms cell biology, we developed an immortalized mouse embryonic fibroblast cell line with conditional disruption of Sdhc and characterize the kinetics of Sdhc gene rearrangement, SDHC protein loss, succinate accumulation, and the resultant hypoproliferative phenotype...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29464052/epigenetic-changes-found-in-uterine-decidual-and-placental-tissues-can-also-be-found-in-the-breast-cancer-microenvironment-of-the-same-unique-patient-description-and-potential-interpretations
#11
Miguel H Bronchud, Francesc Tresserra, Bernat Serra Zantop
Microenvironmental properties are thought to be responsible for feto-maternal tolerance. Speculatively, ectopic expression of placental gene programs might also be related to cancer cells' ability to escape from immune vigilance mechanisms during carcinogenesis and cancer progression. Recently, we published the first human genomic evidence of similar immune related gene expression profiles in both placenta (placenta and decidual tissue) and cancer (both primary and metastatic) in the same patient with lymph-node positive breast carcinoma during pregnancy...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29463682/metabolism-in-pluripotency-both-driver-and-passenger
#12
Perrine Dahan, Vivian Lu, Robert M T Nguyen, Stephanie A L Kennedy, Michael A Teitell
Pluripotent stem cells (PSCs) are highly proliferative cells characterized by robust metabolic demands to power rapid division. For many years considered a passive component or "passenger" of cell fate determination, cell metabolism is now starting to take center stage as a driver of cell fate outcomes. This review provides an update and analysis of our current understanding of PSC metabolism and its role in self-renewal, differentiation, and somatic cell reprogramming to pluripotency. Moreover, we present evidence on the active roles metabolism plays in shaping the epigenome to influence patterns of gene expression that may model key features of early embryonic development...
February 20, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29462323/longitudinal-analysis-strategies-for-modelling-epigenetic-trajectories
#13
James R Staley, Matthew Suderman, Andrew J Simpkin, Tom R Gaunt, Jon Heron, Caroline L Relton, Kate Tilling
Background: DNA methylation levels are known to vary over time, and modelling these trajectories is crucial for our understanding of the biological relevance of these changes over time. However, due to the computational cost of fitting multilevel models across the epigenome, most trajectory modelling efforts to date have focused on a subset of CpG sites identified through epigenome-wide association studies (EWAS) at individual time-points. Methods: We propose using linear regression across the repeated measures, estimating cluster-robust standard errors using a sandwich estimator, as a less computationally intensive strategy than multilevel modelling...
February 16, 2018: International Journal of Epidemiology
https://www.readbyqxmd.com/read/29461653/geneticsepigenetic-marks-of-in-utero-exposure-to-gestational-diabetes-and-childhood-adiposity-outcomes-the-epoch-study
#14
I V Yang, W Zhang, E J Davidson, T E Fingerlin, K Kechris, D Dabelea
AIMS: To identify gestational diabetes mellitus exposure-associated DNA methylation changes and assess whether such changes are also associated with adiposity-related outcomes. METHODS: We performed an epigenome-wide association analysis, using Illumina 450k methylation arrays, on whole blood collected, on average, at 10.5 years of age from 81 gestational diabetes-exposed and 81 unexposed offspring enrolled in the EPOCH (Exploring Perinatal Outcomes in Children) study, and on the cord blood of 31 gestational diabetes-exposed and 64 unexposed offspring enrolled in our own 'Healthy Start' cohort...
February 20, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29460649/identification-of-potential-lifestyle-responsive-epigenomic-biomarkers-in-healthy-women-aged-18-40
#15
Michelle Thunders, Victoria Chinn, Jaret Bilewitch, Peter Stockwell
CONTEXT: Human health is complex and multifaceted; there is a need for biomarkers that reflect the multidimensional nature of health. OBJECTIVE: To identify potential epigenomic biomarkers of health in women aged 18-40 participating in a 6 month lifestyle intervention, Next Level Health. MATERIALS AND METHODS: Methylation data were obtained by Reduced Representation Bisulfite Sequencing of 21 women intervention participants as well as 3 non-participants...
February 20, 2018: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/29459678/evolutionary-analysis-indicates-that-dna-alkylation-damage-is-a-byproduct-of-cytosine-dna-methyltransferase-activity
#16
Silvana Rošić, Rachel Amouroux, Cristina E Requena, Ana Gomes, Max Emperle, Toni Beltran, Jayant K Rane, Sarah Linnett, Murray E Selkirk, Philipp H Schiffer, Allison J Bancroft, Richard K Grencis, Albert Jeltsch, Petra Hajkova, Peter Sarkies
Methylation at the 5 position of cytosine in DNA (5meC) is a key epigenetic mark in eukaryotes. Once introduced, 5meC can be maintained through DNA replication by the activity of 'maintenance' DNA methyltransferases (DNMTs). Despite their ancient origin, DNA methylation pathways differ widely across animals, such that 5meC is either confined to transcribed genes or lost altogether in several lineages. We used comparative epigenomics to investigate the evolution of DNA methylation. Although the model nematode Caenorhabditis elegans lacks DNA methylation, more basal nematodes retain cytosine DNA methylation, which is targeted to repeat loci...
February 19, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29458203/precision-pharmacology-for-alzheimer-s-disease
#17
REVIEW
Harald Hampel, Andrea Vergallo, Lisi Flores Aguilar, Norbert Benda, Karl Broich, A Claudio Cuello, Jeffrey Cummings, Bruno Dubois, Howard J Federoff, Massimo Fiandaca, Remy Genthon, Marion Haberkamp, Eric Karran, Mark Mapstone, George Perry, Lon S Schneider, Lindsay A Welikovitch, Janet Woodcock, Filippo Baldacci, Simone Lista
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses...
February 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29457866/epigenetic-effects-of-metformin-from-molecular-mechanisms-to-clinical-implications
#18
REVIEW
S C Bridgeman, G C Ellison, P E Melton, P Newsholme, Cds Mamotte
There is a growing body of evidence that links epigenetic modifications to type 2 diabetes. Researchers have more recently investigated effects of commonly used medications, including those prescribed for diabetes, on epigenetic processes. This work reviews the influence of the widely used antidiabetic drug metformin on epigenomics, microRNA levels and subsequent gene expression and potential clinical implications. Metformin may influence the activity of numerous epigenetic modifying enzymes, mostly via modulating the activation of AMP-activated protein kinase (AMPK)...
February 19, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29456765/peripheral-blood-epi-signature-of-claes-jensen-syndrome-enables-sensitive-and-specific-identification-of-patients-and-healthy-carriers-with-pathogenic-mutations-in-kdm5c
#19
Laila C Schenkel, Erfan Aref-Eshghi, Cindy Skinner, Peter Ainsworth, Hanxin Lin, Guillaume Paré, David I Rodenhiser, Charles Schwartz, Bekim Sadikovic
Background: Claes-Jensen syndrome is an X-linked inherited intellectual disability caused by mutations in the KDM5C gene. Kdm5c is a histone lysine demethylase involved in histone modifications and chromatin remodeling. Males with hemizygous mutations in KDM5C present with intellectual disability and facial dysmorphism, while most heterozygous female carriers are asymptomatic. We hypothesized that loss of Kdm5c function may influence other components of the epigenomic machinery including DNA methylation in affected patients...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29456242/bacterial-pathogenesis-channelling-the-host-epigenome
#20
Andrea Du Toit
No abstract text is available yet for this article.
February 19, 2018: Nature Reviews. Microbiology
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