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https://www.readbyqxmd.com/read/28342734/integration-of-microbiome-and-epigenome-to-decipher-the-pathogenesis-of-autoimmune-diseases
#1
REVIEW
Beidi Chen, Luxi Sun, Xuan Zhang
The interaction between genetic predisposition and environmental factors are of great significance in the pathogenesis and development of autoimmune diseases (AIDs). The human mucosa is the most frequent site that interacts with the exterior environment, and commensal microbiota at the gut and other human mucosal cavities play a crucial role in the regulation of immune system. Growing evidence has shown that the compositional and functional changes of mucosal microbiota are closely related to AIDs. Gut dysbiosis not only influence the expression level of Toll-like receptors (TLRs) of antigen presenting cells, but also contribute to Th17/Treg imbalance...
March 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28339517/omics-studies-their-use-in-diagnosis-and-reclassification-of-sle-and-other-systemic-autoimmune-diseases
#2
Maria Teruel, Chris Chamberlain, Marta E Alarcón-Riquelme
Omics studies of systemic autoimmune diseases (SADs) in general, and SLE in particular, have delivered isolated information from transcriptome, epigenome, genome, cytokine and metabolome analyses. Such analyses have resulted in the identification of disease susceptibility genes and the description of IFN expression signatures, allowing extensive insight into the mechanisms of disease and the development of new therapies. Access to such technologies allows the recognition of patterns of disease at a pathway level, thereby, to reclassify SLE and other SADs and to develop new therapeutics from a personalized perspective...
October 19, 2016: Rheumatology
https://www.readbyqxmd.com/read/28337071/international-standards-for-genomes-transcriptomes-and-metagenomes
#3
Christopher E Mason, Ebrahim Afshinnekoo, Scott Tighe, Shixiu Wu, Shawn Levy
Challenges and biases in preparing, characterizing, and sequencing DNA and RNA can have significant impacts on research in genomics across all kingdoms of life, including experiments in single-cells, RNA profiling, and metagenomics (across multiple genomes). Technical artifacts and contamination can arise at each point of sample manipulation, extraction, sequencing, and analysis. Thus, the measurement and benchmarking of these potential sources of error are of paramount importance as next-generation sequencing (NGS) projects become more global and ubiquitous...
March 17, 2017: Journal of Biomolecular Techniques: JBT
https://www.readbyqxmd.com/read/28335457/the-epigenetic-link-between-prenatal-adverse-environments-and-neurodevelopmental-disorders
#4
REVIEW
Marija Kundakovic, Ivana Jaric
Prenatal adverse environments, such as maternal stress, toxicological exposures, and viral infections, can disrupt normal brain development and contribute to neurodevelopmental disorders, including schizophrenia, depression, and autism. Increasing evidence shows that these short- and long-term effects of prenatal exposures on brain structure and function are mediated by epigenetic mechanisms. Animal studies demonstrate that prenatal exposure to stress, toxins, viral mimetics, and drugs induces lasting epigenetic changes in the brain, including genes encoding glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf)...
March 18, 2017: Genes
https://www.readbyqxmd.com/read/28334937/dynamically-and-epigenetically-coordinated-gata-ets-sox-transcription-factor-expression-is-indispensable-for-endothelial-cell-differentiation
#5
Yasuharu Kanki, Ryo Nakaki, Teppei Shimamura, Taichi Matsunaga, Kohei Yamamizu, Shiori Katayama, Jun-Ichi Suehiro, Tsuyoshi Osawa, Hiroyuki Aburatani, Tatsuhiko Kodama, Youichiro Wada, Jun K Yamashita, Takashi Minami
Although studies of the differentiation from mouse embryonic stem (ES) cells to vascular endothelial cells (ECs) provide an excellent model for investigating the molecular mechanisms underlying vascular development, temporal dynamics of gene expression and chromatin modifications have not been well studied. Herein, using transcriptomic and epigenomic analyses based on H3K4me3 and H3K27me3 modifications at a genome-wide scale, we analysed the EC differentiation steps from ES cells and crucial epigenetic modifications unique to ECs...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334849/icf-specific-dnmt3b-dysfunction-interferes-with-intragenic-regulation-of-mrna-transcription-and-alternative-splicing
#6
Sole Gatto, Miriam Gagliardi, Monica Franzese, Sylwia Leppert, Mariarosaria Papa, Marco Cammisa, Giacomo Grillo, Guillame Velasco, Claire Francastel, Shir Toubiana, Maurizio D'Esposito, Claudia Angelini, Maria R Matarazzo
Hypomorphic mutations in DNA-methyltransferase DNMT3B cause majority of the rare disorder Immunodeficiency, Centromere instability and Facial anomalies syndrome cases (ICF1). By unspecified mechanisms, mutant-DNMT3B interferes with lymphoid-specific pathways resulting in immune response defects. Interestingly, recent findings report that DNMT3B shapes intragenic CpG-methylation of highly-transcribed genes. However, how the DNMT3B-dependent epigenetic network modulates transcription and whether ICF1-specific mutations impair this process remains unknown...
March 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334349/deepbluer-large-scale-epigenomic-analysis-in-r
#7
Felipe Albrecht, Markus List, Christoph Bock, Thomas Lengauer
Motivation: While large amounts of epigenomic data are publicly available, their retrieval in a form suitable for downstream analysis is a bottleneck in current research. The DeepBlue Epigenomic Data Server provides a powerful interface and API for filtering, transforming, aggregating and downloading data from several epigenomic consortia. Results: To make public epigenomic data conveniently available for analysis in R, we developed an R/Bioconductor package that connects to the DeepBlue Epigenomic Data Server, enabling users to quickly gather and transform epigenomic data from selected experiments for analysis in the Bioconductor ecosystem...
February 22, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28333948/epigenomic-annotation-of-noncoding-mutations-identifies-mutated-pathways-in-primary-liver-cancer
#8
Rebecca F Lowdon, Ting Wang
Evidence that noncoding mutation can result in cancer driver events is mounting. However, it is more difficult to assign molecular biological consequences to noncoding mutations than to coding mutations, and a typical cancer genome contains many more noncoding mutations than protein-coding mutations. Accordingly, parsing functional noncoding mutation signal from noise remains an important challenge. Here we use an empirical approach to identify putatively functional noncoding somatic single nucleotide variants (SNVs) from liver cancer genomes...
2017: PloS One
https://www.readbyqxmd.com/read/28332503/a-chemical-probe-toolbox-for-dissecting-the-cancer-epigenome
#9
Jake Shortt, Christopher J Ott, Ricky W Johnstone, James E Bradner
No abstract text is available yet for this article.
March 23, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28329686/demethylated-hsatii-dna-and-hsatii-rna-foci-sequester-prc1-and-mecp2-into-cancer-specific-nuclear-bodies
#10
Lisa L Hall, Meg Byron, Dawn M Carone, Troy W Whitfield, Gayle P Pouliot, Andrew Fischer, Peter Jones, Jeanne B Lawrence
This study reveals that high-copy satellite II (HSATII) sequences in the human genome can bind and impact distribution of chromatin regulatory proteins and that this goes awry in cancer. In many cancers, master regulatory proteins form two types of cancer-specific nuclear bodies, caused by locus-specific deregulation of HSATII. DNA demethylation at the 1q12 mega-satellite, common in cancer, causes PRC1 aggregation into prominent Cancer-Associated Polycomb (CAP) bodies. These loci remain silent, whereas HSATII loci with reduced PRC1 become derepressed, reflecting imbalanced distribution of UbH2A on these and other PcG-regulated loci...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28329684/cis-regulatory-circuits-regulating-nek6-kinase-overexpression-in-transformed-b-cells-are-super-enhancer-independent
#11
Yue Huang, Olivia I Koues, Jiang-Yang Zhao, Regina Liu, Sarah C Pyfrom, Jacqueline E Payton, Eugene M Oltz
Alterations in distal regulatory elements that control gene expression underlie many diseases, including cancer. Epigenomic analyses of normal and diseased cells have produced correlative predictions for connections between dysregulated enhancers and target genes involved in pathogenesis. However, with few exceptions, these predicted cis-regulatory circuits remain untested. Here, we dissect cis-regulatory circuits that lead to overexpression of NEK6, a mitosis-associated kinase, in human B cell lymphoma. We find that only a minor subset of predicted enhancers is required for NEK6 expression...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28325913/persistent-dna-methylation-changes-associated-with-prenatal-mercury-exposure-and-cognitive-performance-during-childhood
#12
Andres Cardenas, Sheryl L Rifas-Shiman, Golareh Agha, Marie-France Hivert, Augusto A Litonjua, Dawn L DeMeo, Xihong Lin, Chitra J Amarasiriwardena, Emily Oken, Matthew W Gillman, Andrea A Baccarelli
Prenatal exposure to mercury, a known neurotoxic metal, is associated with lower cognitive performance during childhood. Disruption of fetal epigenetic programming could explain mercury's neurodevelopmental effects. We screened for epigenome-wide methylation differences associated with maternal prenatal blood mercury levels in 321 cord blood DNA samples and examined the persistence of these alterations during early (n = 75; 2.9-4.9 years) and mid-childhood (n = 291; 6.7-10.5 years). Among males, prenatal mercury levels were associated with lower regional cord blood DNA methylation at the Paraoxonase 1 gene (PON1) that persisted in early childhood and was attenuated in mid-childhood blood...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28324153/epigenetics-in-the-pathogenesis-of-ra
#13
REVIEW
Caroline Ospelt, Steffen Gay, Kerstin Klein
Epigenetic modifications can stably alter gene expression and have been shown to be important in the maintenance of cell type-specific functions as well as in cell differentiation, e.g., in T and B cell maturation. In RA, alterations in DNA methylation, histone modifications, and microRNA expression have been found in immune as well as in stromal cells. These changes in the epigenome in RA patients influence key inflammatory and matrix-degrading pathways and are suspected to play a major role in the pathogenesis of RA...
March 21, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28324041/line1-cpg-dna-hypomethylation-in-granulosa-cells-and-blood-leukocytes-is-associated-with-pcos-and-related-traits
#14
Pooja Sagvekar, Vijay Mangoli, Sadhana Desai, Anushree Patil, Srabani Mukherjee
CONTEXT: Altered global DNA methylation is indicative of epigenomic instability concerning chronic disease-states. Investigating its incidence and association with polycystic ovary syndrome (PCOS) is essential towards understanding the etiopathogenesis of this disorder. OBJECTIVES: To assess, global DNA methylation differences in peripheral blood leukocytes (PBLs) and cumulus granulosa cells (CGCs) of PCOS and controls and their association with PCOS and its traits...
January 9, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28322586/the-neonatal-methylome-as-a-gatekeeper-in-the-trajectory-to-childhood-asthma
#15
Avery DeVries, Donata Vercelli
Asthma is a heterogeneous group of conditions that typically begin in early life and result in recurrent, reversible bronchial obstruction. The role played by epigenetic mechanisms in the pathogenesis of childhood asthma is understood only in part. Here we discuss asthma epigenetics within a developmental perspective based on our recent demonstration that the epigenetic trajectory to childhood asthma begins at birth. We next discuss how this trajectory may be affected by prenatal environmental exposures. Finally, we examine in vitro studies that model the impact of asthma-associated exposures on the epigenome...
March 21, 2017: Epigenomics
https://www.readbyqxmd.com/read/28322583/interplay-between-genetic-and-epigenetic-mechanisms-in-rheumatoid-arthritis
#16
Mojca Frank-Bertoncelj, Kerstin Klein, Steffen Gay
Genetic and environmental factors contribute to the risk for rheumatoid arthritis (RA), with epigenetics serving as a possible interface through which risk factors contribute to RA. High-throughput technologies for interrogating genome and epigenome, and the availability of genetic and epigenetic datasets across a diversity of cell types, enable the identification of candidate causal genetic variants for RA to study their function in core RA processes. To date, RA risk variants were studied in the immune cells but not joint resident cells, for example, synovial fibroblasts...
March 21, 2017: Epigenomics
https://www.readbyqxmd.com/read/28322581/epigenetics-and-allergy-from-basic-mechanisms-to-clinical-applications
#17
Daniel P Potaczek, Hani Harb, Sven Michel, Bilal Alashkar Alhamwe, Harald Renz, Jörg Tost
Allergic diseases are on the rise in the Western world and well-known allergy-protecting and -driving factors such as microbial and dietary exposure, pollution and smoking mediate their influence through alterations of the epigenetic landscape. Here, we review key facts on the involvement of epigenetic modifications in allergic diseases and summarize and critically evaluate the lessons learned from epigenome-wide association studies. We show the potential of epigenetic changes for various clinical applications: as diagnostic tools, to assess tolerance following immunotherapy or possibly predict the success of therapy at an early time point...
March 21, 2017: Epigenomics
https://www.readbyqxmd.com/read/28322575/epigenome-wide-dna-methylation-study-of-ige-concentration-in-relation-to-self-reported-allergies
#18
Weronica E Ek, Muhammad Ahsan, Mathias Rask-Andersen, Liming Liang, Miriam F Moffatt, Ulf Gyllensten, Åsa Johansson
AIM: Epigenetic mechanisms are critical for normal immune development and epigenetic alterations might therefore be possible contributors to immune diseases. To investigate if DNA methylation in whole blood is associated with total and allergen-specific IgE levels. METHODS: We performed an epigenome-wide association study to investigate the association between DNA methylation and IgE level, allergen-specific IgE and self-reported immune diseases and allergies in 728 individuals...
March 21, 2017: Epigenomics
https://www.readbyqxmd.com/read/28322272/neuroanatomic-epigenetic-and-genetic-differences-in-monozygotic-twins-discordant-for-attention-deficit-hyperactivity-disorder
#19
Y-C Chen, G Sudre, W Sharp, F Donovan, S C Chandrasekharappa, N Hansen, L Elnitski, P Shaw
The study of monozygotic twins discordant for attention deficit hyperactivity disorder can elucidate mechanisms that contribute to the disorder, which affects ~7% of children. First, using in vivo neuroanatomic imaging on 14 pairs of monozygotic twins (mean age 9.7, s.d. 1.9 years), we found that discordance for the disorder is mirrored by differing dimensions of deep brain structures (the striatum and cerebellum), but not the cerebral cortex. Next, using whole-blood DNA from the same twins, we found a significant enrichment of epigenetic differences in genes expressed in these 'discordant' brain structures...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28320934/allele-specific-non-cg-dna-methylation-marks-domains-of-active-chromatin-in-female-mouse-brain
#20
Christopher L Keown, Joel B Berletch, Rosa Castanon, Joseph R Nery, Christine M Disteche, Joseph R Ecker, Eran A Mukamel
DNA methylation at gene promoters in a CG context is associated with transcriptional repression, including at genes silenced on the inactive X chromosome in females. Non-CG methylation (mCH) is a distinct feature of the neuronal epigenome that is differentially distributed between males and females on the X chromosome. However, little is known about differences in mCH on the active (Xa) and inactive (Xi) X chromosomes because stochastic X-chromosome inactivation (XCI) confounds allele-specific epigenomic profiling...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
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