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Epigenome

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https://www.readbyqxmd.com/read/28934561/epigenetic-mechanisms-regulating-adaptive-responses-to-targeted-kinase-inhibitors-in-cancer
#1
Steven P Angus, Jon S Zawistowski, Gary L Johnson
Although targeted inhibition of oncogenic kinase drivers has achieved remarkable patient responses in many cancers, the development of resistance has remained a significant challenge. Numerous mechanisms have been identified, including the acquisition of gatekeeper mutations, activating pathway mutations, and copy number loss or gain of the driver or alternate nodes. These changes have prompted the development of kinase inhibitors with increased selectivity, use of second-line therapeutics to overcome primary resistance, and combination treatment to forestall resistance...
September 15, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28934481/automatic-identification-of-informative-regions-with-epigenomic-changes-associated-to-hematopoiesis
#2
Enrique Carrillo-de-Santa-Pau, David Juan, Vera Pancaldi, Felipe Were, Ignacio Martin-Subero, Daniel Rico, Alfonso Valencia
Hematopoiesis is one of the best characterized biological systems but the connection between chromatin changes and lineage differentiation is not yet well understood. We have developed a bioinformatic workflow to generate a chromatin space that allows to classify 42 human healthy blood epigenomes from the BLUEPRINT, NIH ROADMAP and ENCODE consortia by their cell type. This approach let us to distinguish different cells types based on their epigenomic profiles, thus recapitulating important aspects of human hematopoiesis...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934364/the-histone-variant-macroh2a-confers-functional-robustness-to-the-intestinal-stem-cell-compartment
#3
Ryan James Cedeno, Angela Nakauka-Ddamba, Maryam Yousefi, Stephanie Sterling, Nicolae Adrian Leu, Ning Li, John R Pehrson, Christopher Joachim Lengner
A stem cell's epigenome directs cell fate during development, homeostasis, and regeneration. Epigenetic dysregulation can lead to inappropriate cell fate decisions, aberrant cell function, and even cancer. The histone variant macroH2A has been shown to influence gene expression, guide cell fate, and safeguard against genotoxic stress. Interestingly, mice lacking functional macroH2A histones (hereafter referred to as macroH2A DKO) are viable and fertile; yet suffer from increased perinatal death and reduced weight and size compared to wildtype (WT)...
2017: PloS One
https://www.readbyqxmd.com/read/28933651/characterization-of-h3-3k36m-as-a-tool-to-study-h3k36-methylation-in-cancer-cells
#4
Saumya M Sankaran, Or Gozani
Recurrent mutations at key lysine residues in the histone variant H3.3 are thought to play an etiologic role in the development of distinct subsets of pediatric gliomas and bone and cartilage cancers. H3.3K36M is one such mutation that was originally identified in chondroblastomas, and its expression in these tumors contributes to oncogenic reprogramming by triggering global depletion of dimethylation and trimethylation at H3K36 with a concomitant increase in the levels of H3K27 trimethylation. H3.3K36M expression can also cause epigenomic changes in cell types beyond chondrocytic cells...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28933105/-nrf2-nf-%C3%AE%C2%BAb-pathway-axes-epigenetic-regulation-and-traditional-chinese-medicine-natural-medicine-to-treat-type-2-diabetes
#5
REVIEW
Chun-Mei Zhai, Bo-Yu Jia, Zhi-Bin Wang, Xue Huai, Zhi-Chao Ma, Zhen-Kun Tian, Yong-Hai Meng
Diabetes mellitus is a characterized by high blood sugar metabolic disease, is a lifelong disease with a high incidence of major hazards. Prevention and treatment of diabetes and its complications has become a serious challenge and arduous task facing the world pharmaceutical researchers. Oxidative stress, Nfr2-NF-κB signaling axis related epigenomic genes have the apparent close relationship with type 2 diabetes,those have become one of the key focus and effective way to explore its pathogenesis, mechanism and drug screening...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28931935/alpha-tc1-and-beta-tc-6-genomic-profiling-uncovers-both-shared-and-distinct-transcriptional-regulatory-features-with-their-primary-islet-counterparts
#6
Nathan Lawlor, Ahrim Youn, Romy Kursawe, Duygu Ucar, Michael L Stitzel
Alpha TC1 (αTC1) and Beta-TC-6 (βTC6) mouse islet cell lines are cellular models of islet (dys)function and type 2 diabetes (T2D). However, genomic characteristics of these cells, and their similarities to primary islet alpha and beta cells, are undefined. Here, we report the epigenomic (ATAC-seq) and transcriptomic (RNA-seq) landscapes of αTC1 and βTC6 cells. Each cell type exhibits hallmarks of its primary islet cell counterpart including cell-specific expression of beta (e.g., Pdx1) and alpha (e.g., Arx) cell transcription factors (TFs), and enrichment of binding motifs for these TFs in αTC1/βTC6 cis-regulatory elements...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931564/towards-precision-medicine-for-hypertension-a-review-of-genomic-epigenomic-and-microbiomic-effects-on-blood-pressure-in-experimental-rat-models-and-humans
#7
REVIEW
Sandosh Padmanabhan, Bina Joe
Compelling evidence for the inherited nature of essential hypertension has led to extensive research in rats and humans. Rats have served as the primary model for research on the genetics of hypertension resulting in identification of genomic regions that are causally associated with hypertension. In more recent times, genome-wide studies in humans have also begun to improve our understanding of the inheritance of polygenic forms of hypertension. Based on the chronological progression of research into the genetics of hypertension as the "structural backbone," this review catalogs and discusses the rat and human genetic elements mapped and implicated in blood pressure regulation...
October 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28931409/clinical-review-of-24-35%C3%A2-year-olds-conceived-with-and-without-in-vitro-fertilization-study-protocol
#8
Sharon Lewis, Joanne Kennedy, David Burgner, Robert McLachlan, Sarath Ranganathan, Karin Hammarberg, Richard Saffery, David J Amor, Michael M H Cheung, Lex W Doyle, Markus Juonala, Susan Donath, John McBain, Jane Halliday
BACKGROUND: Children conceived by assisted reproductive technologies (ART) currently comprise 4% of Australian births. The manipulation of biological parameters related to fertilization and implantation are integral to successful ART but potentially pose a risk to the longer-term health of the offspring. There is consensus that many common adult health problems (particularly cardiovascular, metabolic and respiratory conditions) have their origins in early life, possibly before birth, and that risk trajectories track through childhood until clinical disease manifests in adulthood...
September 20, 2017: Reproductive Health
https://www.readbyqxmd.com/read/28930691/dna-methylome-analysis-identifies-transcription-factor-based-epigenomic-signatures-of-multilineage-competence-in-neural-stem-progenitor-cells
#9
Tsukasa Sanosaka, Takuya Imamura, Nobuhiko Hamazaki, MuhChyi Chai, Katsuhide Igarashi, Maky Ideta-Otsuka, Fumihito Miura, Takashi Ito, Nobuyuki Fujii, Kazuho Ikeo, Kinichi Nakashima
Regulation of the epigenome during in vivo specification of brain stem cells is still poorly understood. Here, we report DNA methylome analyses of directly sampled cortical neural stem and progenitor cells (NS/PCs) at different development stages, as well as those of terminally differentiated cortical neurons, astrocytes, and oligodendrocytes. We found that sequential specification of cortical NS/PCs is regulated by two successive waves of demethylation at early and late development stages, which are responsible for the establishment of neuron- and glia-specific low-methylated regions (LMRs), respectively...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930592/choline-the-brain-and-neurodegeneration-insights-from-epigenetics
#10
Rola A Bekdash
  Neurodegenerative disorders are a major public health problem worldwide with huge socioeconomic effect. Recent evidence suggests that neurodegeneration is not only caused by genetic factors but also affected by environmental factors including nutrients. Environmental influences have been shown to cause epigenetic modifications in the brain with long-lasting effects on behavior if they occur in early life. It has been suggested that early nutritional intervention that includes choline, betaine, VitB6, VitB12 and/or folic acid could attenuate decline in cognitive functions...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28929968/c-state-an-interactive-web-app-for-simultaneous-multi-gene-visualization-and-comparative-epigenetic-pattern-search
#11
Divya Tej Sowpati, Surabhi Srivastava, Jyotsna Dhawan, Rakesh K Mishra
BACKGROUND: Comparative epigenomic analysis across multiple genes presents a bottleneck for bench biologists working with NGS data. Despite the development of standardized peak analysis algorithms, the identification of novel epigenetic patterns and their visualization across gene subsets remains a challenge. RESULTS: We developed a fast and interactive web app, C-State (Chromatin-State), to query and plot chromatin landscapes across multiple loci and cell types...
September 13, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28929670/-herbgenomics
#12
Shi-Lin Chen, Jing-Yuan Song
Traditional Chinese medicine (TCM) has contributad greatly to improving human health. However, the biological characteristics and molecular mechanisms of TCM in the treatment of human diseases remain largely unknown. Genomics plays an important role in modern medicine and biology. Here, we introduce genomics and other related omics to the study of herbs to propose a new discipline, Herbgenomics, that aims to uncover the genetic information and regulatory networks of herbs and to clarify their molecular mechanisms in the prevention and treatment of human diseases...
November 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28928767/genome-wide-epigenetic-characterization-of-tissues-from-three-germ-layers-isolated-from-sheep-fetuses
#13
Emanuele Capra, Paola Toschi, Marcello Del Corvo, Barbara Lazzari, Pier A Scapolo, Pasqualino Loi, John L Williams, Alessandra Stella, Paolo Ajmone-Marsan
DNA methylation of regulatory and growth-related genes contributes to fetal programming which is important for maintaining the correct development of three germ layers of the embryo that develope into different tissues and organs, and which persists into adult life. In this study, a preliminary epigenetic screen was performed to define genomic regions that are involved in fetal epigenome remodeling. Embryonic ectodermic tissues (origin of nervous tissue), mesenchymal tissues (origin of connective and muscular tissues), and foregut endoderm tissues (origin of epithelial tissue), from day 28 sheep fetuses were collected and the distribution of methylated CpGs was analyzed using whole-genome bisulfite sequencing...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28928387/bi-directional-effects-of-vitamin-b12-and-methotrexate-on-daphnia-magna-fitness-and-genomic-methylation
#14
Fitore Kusari, Alan M O'Doherty, Nikolas J Hodges, Marcin W Wojewodzic
Here we interrogated, using three separate but complementary experimental approaches, the impact of vitamin B12 availability and methotrexate exposure on Daphnia magna, which we hypothesised should have an opposite effect on One carbon metabolism (OCM). OCM is a vital biological process supporting a variety of physiological processes, including DNA methylation. Contrary to mammalian models, this process remains largely unexplored in invertebrates. The purpose of this study was to elucidate the impact of OCM short-term alteration on the fitness and epigenome of the keystone species, Daphnia...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28927277/benchmark-dose-modeling-estimates-of-the-concentrations-of-inorganic-arsenic-that-induce-changes-to-the-neonatal-transcriptome-proteome-and-epigenome-in-a-pregnancy-cohort
#15
Julia Rager, Scott S Auerbach, Grace A Chappell, Elizabeth Martin, Chad Thompson, Rebecca C Fry
Prenatal inorganic arsenic (iAs) exposure influences the expression of critical genes and proteins associated with adverse outcomes in newborns, in part through epigenetic mediators. The doses at which these genomic and epigenomic changes occur have yet to be evaluated in the context of dose-response modeling. The goal of the present study was to estimate iAs doses that correspond to changes in transcriptomic, proteomic, epigenomic, and integrated multi-omic signatures in human cord blood through benchmark dose (BMD) modeling...
September 19, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28926427/dna-methylation-targeted-drugs
#16
Elodie M Da Costa, Gabrielle McInnes, Annie Beaudry, Noël J-M Raynal
Targeting DNA hypermethylation, using nucleoside analogs, is an efficient approach to reprogram cancer cell epigenome leading to reduced proliferation, increased differentiation, recognition by the immune system, and ultimately cancer cell death. DNA methyltransferase inhibitors have been approved for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myelogenous leukemia. To improve clinical efficacy and overcome mechanisms of drug resistance, a second generation of DNA methyltransferase inhibitors has been designed and is currently in clinical trials...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28925810/ube3a-mediated-regulation-of-imprinted-genes-and-epigenome-wide-marks-in-human-neurons
#17
S Jesse Lopez, Keith Dunaway, M Saharul Islam, Charles Mordaunt, Annie Vogel Ciernia, Makiko Meguro-Horike, Shin-Ichi Horike, David J Segal, Janine LaSalle
The dysregulation of genes in neurodevelopmental disorders that lead to social and cognitive phenotypes is a complex, multilayered process involving both genetics and epigenetics. Parent-of-origin effects of deletion and duplication of the 15q11-q13 locus leading to Angelman, Prader-Willi, and Dup15q syndromes are due to imprinted genes, including UBE3A, which is maternally expressed exclusively in neurons. UBE3A encodes a ubiquitin E3 ligase protein with multiple downstream targets, including RING1B, which in turn monoubiquitinates histone variant H2A...
September 19, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28925547/biogeographic-conservation-of-the-cytosine-epigenome-in-the-globally-important-marine-nitrogen-fixing-cyanobacterium-trichodesmium
#18
Nathan G Walworth, David A Hutchins, Egor Dolzhenko, Michael D Lee, Feixue Fu, Andrew D Smith, Eric A Webb
Cytosine methylation has been shown to regulate essential cellular processes and impact biological adaptation. Despite its evolutionary importance, only a handful of bacterial, genome-wide cytosine studies have been conducted, with none for marine bacteria. Here, we examine the genome-wide, C(5) -Methyl-cytosine (m5C) methylome and its correlation to global transcription in the marine nitrogen-fixing cyanobacterium Trichodesmium. We characterize genome-wide methylation and highlight conserved motifs across 3 Trichodesmium isolates and 2 Trichodesmium metagenomes, thereby identifying highly conserved, novel genomic signatures of potential gene regulation in Trichodesmium...
September 19, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28923782/single-cell-epigenome-sequencing-technologies
#19
REVIEW
Lu Wen, Fuchou Tang
No abstract text is available yet for this article.
September 16, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28923089/dna-epigenome-editing-using-crispr-cas-suntag-directed-dnmt3a
#20
Yung-Hsin Huang, Jianzhong Su, Yong Lei, Lorenzo Brunetti, Michael C Gundry, Xiaotian Zhang, Mira Jeong, Wei Li, Margaret A Goodell
BACKGROUND: DNA methylation has widespread effects on gene expression during development. However, our ability to assign specific function to regions of DNA methylation is limited by the poor correlation between global patterns of DNA methylation and gene expression. RESULTS: Here, we utilize nuclease-deactivated Cas9 protein fused to repetitive peptide epitopes (SunTag) recruiting multiple copies of antibody-fused de novo DNA methyltransferase 3A (DNMT3A) (dCas9-SunTag-DNMT3A) to amplify the local DNMT3A concentration to methylate genomic sites of interest...
September 18, 2017: Genome Biology
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