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Methylomics

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https://www.readbyqxmd.com/read/28423671/genome-wide-dna-methylation-analysis-reveals-molecular-subtypes-of-pancreatic-cancer
#1
Nitish Kumar Mishra, Chittibabu Guda
Pancreatic cancer (PC) is the fourth leading cause of cancer deaths in the United States with a five-year patient survival rate of only 6%. Early detection and treatment of this disease is hampered due to lack of reliable diagnostic and prognostic markers. Recent studies have shown that dynamic changes in the global DNA methylation and gene expression patterns play key roles in the PC development; hence, provide valuable insights for better understanding the initiation and progression of PC. In the current study, we used DNA methylation, gene expression, copy number, mutational and clinical data from pancreatic patients...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418886/histone-hypoacetylation-contributes-to-cxcl12-downregulation-in-colon-cancer-impact-on-tumor-growth-and-cell-migration
#2
Benoît Romain, Radhia Benbrika-Nehmar, Laetitia Marisa, Michèle Legrain, Viviane Lobstein, Attila Oravecz, Laetitia Poidevin, Cyril Bour, Jean-Noël Freund, Isabelle Duluc, Dominique Guenot, Erwan Pencreach
CXCL12 has been shown to be involved in colon cancer metastasis, but its expression level and molecular mechanisms regulating its expression remain controversial. We thus evaluated CXCL12 expression in a large cohort of colon adenomas and carcinomas, investigated for an epigenetic mechanism controlling its expression and evaluated the impact of CXCL12 levels on cell migration and tumor growth. CXCL12 expression was measured in human colon adenomas and carcinomas with transcriptome array and RT-qPCR. The promoter methylation was analyzed with whole-genome DNA methylation chips and protein expression by immunohistochemistry...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409894/genomic-responses-of-mouse-synovial-fibroblasts-during-tnf-driven-arthritogenesis-greatly-mimic-those-of-human-rheumatoid-arthritis
#3
Evangelos Ntougkos, Panagiotis Chouvardas, Fani Roumelioti, Caroline Ospelt, Mojka Frank-Bertoncelj, Andrew Filer, Christopher D Buckley, Steffen Gay, Christoforos Nikolaou, George Kollias
OBJECTIVE: Aberrant activation of synovial fibroblasts (SFs) is a key determinant in the pathogenesis of rheumatoid arthritis (RA). We aimed to produce a map of gene expression and epigenetic changes occurring in this cell type during disease progression in the human TNF-transgenic model of arthritis, and identify commonalities with human SFs. METHODS: We used deep sequencing to probe the transcriptome, the methylome and the chromatin landscape of cultured mouse arthritogenic SFs at three stages of disease, as well as SFs stimulated with human TNF...
April 13, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28408400/epigenetic-identity-in-aml-depends-on-disruption-of-non-promoter-regulatory-elements-and-is-affected-by-antagonistic-effects-of-mutations-in-epigenetic-modifiers
#4
Jacob Glass, Duane C Hassane, Bas Wouters, Hiroyoshi Kunimoto, Roberto Avellino, Francine E Garrett-Bakelman, Olga A Guryanova, Robert Bowman, Shira Redlich, Andrew Intlekofer, Cem Meydan, Tingting Qin, Mame P Fall, Alicia Alonso, Monica L Guzman, Peter Jm Valk, Craig B Thompson, Ross L Levine, Olivier Elemento, Ruud Delwel, Ari Melnick, Maria E Figueroa
Aberrant DNA methylation of gene promoters is a hallmark of AML. To define more precisely how cytosine methylation is redistributed in AML, we performed base-pair resolution methylome sequencing in 119 patients. We find that leukemic DNA methylation patterning is tightly linked to somatic mutations and primarily driven by regulatory elements outside of promoters and by CpG shores as opposed to CpG islands. Active enhancers displayed much stronger focal differential methylation than promoters and were generally aberrantly hypomethylated except in IDH2 mutant and CEBPA silenced AMLs...
April 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28407801/single-base-resolution-methylomes-of-upland-cotton-gossypium-hirsutum-l-reveal-epigenome-modifications-in-response-to-drought-stress
#5
Xuke Lu, Xiaoge Wang, Xiugui Chen, Na Shu, Junjuan Wang, Delong Wang, Shuai Wang, Weili Fan, Lixue Guo, Xiaoning Guo, Wuwei Ye
BACKGROUND: DNA methylation, with a cryptic role in genome stability, gene transcription and expression, is involved in the drought response process in plants, but the complex regulatory mechanism is still largely unknown. RESULTS: Here, we performed whole-genome bisulfite sequencing (WGBS) and identified long non-coding RNAs on cotton leaves under drought stress and re-watering treatments. We obtained 31,223 and 30,997 differentially methylated regions (representing 2...
April 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28406917/methylomic-changes-in-individuals-with-psychosis-prenatally-exposed-to-endocrine-disrupting-compounds-lessons-from-diethylstilbestrol
#6
Fabrice Rivollier, Boris Chaumette, Narjes Bendjemaa, Mélanie Chayet, Bruno Millet, Nematollah Jaafari, Amina Barhdadi, Louis-Philippe Lemieux Perreault, Sylvie Provost, Marie-Pierre Dubé, Raphaël Gaillard, Marie-Odile Krebs, Oussama Kebir
BACKGROUND: In the Western world, between 1940 and 1970, more than 2 million people were exposed in utero to diethylstilbestrol (DES). In exposed individuals, and in their descendants, adverse outcomes have been linked to such exposure, including cancers, genital malformations, and less consistently, psychiatric disorders. We aimed to explore whether prenatal DES exposure would be associated with DNA methylation changes, and whether these epigenetic modifications would be associated with increased risk of psychosis...
2017: PloS One
https://www.readbyqxmd.com/read/28385611/description-of-the-eurotarget-cohort-a-european-collaborative-project-on-targeted-therapy-in-renal-cell-cancer-genetic-and-tumor-related-biomarkers-for-response-and-toxicity
#7
Loes F M van der Zanden, Sita H Vermeulen, Arna Oskarsdottir, Jake S F Maurits, Meta H M Diekstra, Valentin Ambert, Anne Cambon-Thomsen, Daniel Castellano, Achim Fritsch, Jesus Garcia Donas, Rosa Guarch Troyas, Henk-Jan Guchelaar, Arndt Hartmann, Christina Hulsbergen-van de Kaa, Ulrich Jaehde, Kerstin Junker, Anna Martinez-Cardus, Gisli Masson, Jeannette Oosterwijk-Wakka, Marius T Radu, Thorunn Rafnar, Cristina Rodriguez-Antona, Max Roessler, Rob Ruijtenbeek, Kari Stefansson, Anne Warren, Lodewyk Wessels, Tim Eisen, Lambertus A L M Kiemeney, Egbert Oosterwijk
OBJECTIVE: For patients with metastatic renal cell cancer (mRCC), treatment choice is mainly based on clinical parameters. With many treatments available and the limited response to treatment and associated toxicities, there is much interest in identifying better biomarkers for personalized treatment. EuroTARGET aims to identify and characterize host- and tumor-related biomarkers for prediction of response to tyrosine kinase inhibitor therapy in mRCC. Here, we describe the EuroTARGET mRCC patient cohort...
April 3, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28381438/modeling-breast-cancer-intertumor-and-intratumor-heterogeneity-using-xenografts
#8
Alejandra Bruna, Oscar M Rueda, Carlos Caldas
Breast cancer is a heterogeneous disease that can be stratified in at least 10 different subtypes. We present here a platform for derivation of preclinical models based on patient-derived tumor xenografts (PDTXs) that represent these subgroups. These models preserve the transcriptome, methylome, copy-number, and mutational landscape features of the tumor of origin through different passaging. Furthermore, the intratumoral composition of these models is formed by communities of clones very similar to the ones present in the originating tumor...
April 5, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28380383/using-dna-methylation-profiling-to-evaluate-biological-age-and-longevity-interventions
#9
Daniel A Petkovich, Dmitriy I Podolskiy, Alexei V Lobanov, Sang-Goo Lee, Richard A Miller, Vadim N Gladyshev
The DNA methylation levels of certain CpG sites are thought to reflect the pace of human aging. Here, we developed a robust predictor of mouse biological age based on 90 CpG sites derived from partial blood DNA methylation profiles. The resulting clock correctly determines the age of mouse cohorts, detects the longevity effects of calorie restriction and gene knockouts, and reports rejuvenation of fibroblast-derived iPSCs. The data show that mammalian DNA methylomes are characterized by CpG sites that may represent the organism's biological age...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28379409/dna-methylation-divergence-and-tissue-specialization-in-the-developing-mouse-placenta
#10
Benjamin E Decato, Jorge Lopez-Tello, Amanda Sferruzzi-Perri, Andrew D Smith, Matthew D Dean
The placental epigenome plays a vital role in regulating mammalian growth and development. Aberrations in placental DNA methylation are linked to several disease states, including intrauterine growth restriction and preeclampsia. Studying the evolution and development of the placental epigenome is critical to understanding the origin and progression of such diseases. Although high resolution studies have found substantial variation between placental methylomes of different species, the nature of methylome variation has yet to be characterized within any individual species...
April 4, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28351423/epigenetic-aging-signatures-in-mice-livers-are-slowed-by-dwarfism-calorie-restriction-and-rapamycin-treatment
#11
Tina Wang, Brian Tsui, Jason F Kreisberg, Neil A Robertson, Andrew M Gross, Michael Ku Yu, Hannah Carter, Holly M Brown-Borg, Peter D Adams, Trey Ideker
BACKGROUND: Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. RESULTS: We first examined whether mice and humans experience similar patterns of change in the methylome with age...
March 28, 2017: Genome Biology
https://www.readbyqxmd.com/read/28349825/methylomics-of-breast-cancer-seeking-epimarkers-in-peripheral-blood-of-young-subjects
#12
Golnaz Khakpour, Mehrdad Noruzinia, Pantea Izadi, Fatemeh Karami, Mohammad Ahmadvand, Ramin Heshmat, Mahsa M Amoli, Javad Tavakkoly-Bazzaz
Critical roles of epigenomic alterations in the pathogenesis of breast cancer have recently seized great attentions toward finding epimarkers in either non-invasive or semi-non-invasive samples as well as peripheral blood. In this way, methylated DNA immunoprecipitation microarray (MeDIP-chip) was performed on DNA samples isolated from white blood cells of 30 breast cancer patients compared to 30 healthy controls. A total of 1799 differentially methylated regions were identified including SLC6A3, Rab40C, ZNF584, and FOXD3 whose significant methylation differences were confirmed in breast cancer patients through quantitative real-time polymerase chain reaction...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28349465/transcriptome-wide-mapping-of-n-1-methyladenosine-methylome
#13
Xiaoyu Li, Jinying Peng, Chengqi Yi
N (1)-Methyladenosine (m(1)A) is a prevalent posttranscriptional RNA modification and commonly found in tRNA and rRNA. Very recent works have also demonstrated the prevalence of m(1)A in mammalian mRNA. Hence, high-throughput methods that allow transcriptome-wide mapping of m(1)A will be important for further functional investigations. Here, we describe a technique called "m(1)A-ID-Seq", which is based on m(1)A immunoprecipitation and the inherent ability of m(1)A to stall reverse transcription, to map m(1)A in the transcriptome...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28346544/epigenetic-silencing-of-v-d-j-recombination-is-a-major-determinant-for-selective-differentiation-of-mucosal-associated-invariant-t-cells-from-induced-pluripotent-stem-cells
#14
Yutaka Saito, Chie Sugimoto, Toutai Mituyama, Hiroshi Wakao
Mucosal-associated invariant T cells (MAITs) are innate-like T cells that play a pivotal role in the host defense against infectious diseases, and are also implicated in autoimmune diseases, metabolic diseases, and cancer. Recent studies have shown that induced pluripotent stem cells (iPSCs) derived from MAITs selectively redifferentiate into MAITs without altering their antigen specificity. Such a selective differentiation is a prerequisite for the use of MAITs in cell therapy and/or regenerative medicine...
2017: PloS One
https://www.readbyqxmd.com/read/28345647/sexual-epigenetics-gender-specific-methylation-of-a-gene-in-the-sex-determining-region-of-populus-balsamifera
#15
Katharina Bräutigam, Raju Soolanayakanahally, Marc Champigny, Shawn Mansfield, Carl Douglas, Malcolm M Campbell, Quentin Cronk
Methylation has frequently been implicated in gender determination in plants. The recent discovery of the sex determining region (SDR) of balsam poplar, Populus balsamifera, pinpointed 13 genes with differentiated X and Y copies. We tested these genes for differential methylation using whole methylome sequencing of xylem tissue of multiple individuals grown under field conditions in two common gardens. The only SDR gene to show a marked pattern of gender-specific methylation is PbRR9, a member of the two component response regulator (type-A) gene family, involved in cytokinin signalling...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28340624/medecom-discovery-and-quantification-of-latent-components-of-heterogeneous-methylomes
#16
Pavlo Lutsik, Martin Slawski, Gilles Gasparoni, Nikita Vedeneev, Matthias Hein, Jörn Walter
It is important for large-scale epigenomic studies to determine and explore the nature of hidden confounding variation, most importantly cell composition. We developed MeDeCom as a novel reference-free computational framework that allows the decomposition of complex DNA methylomes into latent methylation components and their proportions in each sample. MeDeCom is based on constrained non-negative matrix factorization with a new biologically motivated regularization function. It accurately recovers cell-type-specific latent methylation components and their proportions...
March 24, 2017: Genome Biology
https://www.readbyqxmd.com/read/28336599/complete-genome-sequence-and-methylome-analysis-of-acinetobacter-calcoaceticus-65
#17
Alexey Fomenkov, Tamas Vincze, Sergey K Degtyarev, Richard J Roberts
Acinetobacter calcoaceticus 65 is the original source strain for the restriction enzyme Acc65I. Its complete sequence and full methylome were determined using single-molecule real-time (SMRT) sequencing.
March 23, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28334972/enrichment-methods-provide-a-feasible-approach-to-comprehensive-and-adequately-powered-investigations-of-the-brain-methylome
#18
Robin F Chan, Andrey A Shabalin, Lin Y Xie, Daniel E Adkins, Min Zhao, Gustavo Turecki, Shaunna L Clark, Karolina A Aberg, Edwin J C G van den Oord
Methylome-wide association studies are typically performed using microarray technologies that only assay a very small fraction of the CG methylome and entirely miss two forms of methylation that are common in brain and likely of particular relevance for neuroscience and psychiatric disorders. The alternative is to use whole genome bisulfite (WGB) sequencing but this approach is not yet practically feasible with sample sizes required for adequate statistical power. We argue for revisiting methylation enrichment methods that, provided optimal protocols are used, enable comprehensive, adequately powered and cost-effective genome-wide investigations of the brain methylome...
February 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334074/genome-wide-analysis-reveals-that-exon-methylation-facilitates-its-selective-usage-in-the-human-transcriptome
#19
Shengli Li, Jiwei Zhang, Shenglin Huang, Xianghuo He
DNA methylation, especially in promoter regions, is a well-characterized epigenetic marker related to gene expression regulation in eukaryotes. However, the role of intragenic DNA methylation in the usage of corresponding exons still remains elusive. In this study, we described the DNA methylome across 10 human tissues. The human genome showed both conserved and varied methylation levels among these tissues. We found that the methylation densities in promoters and first exons were negatively correlated with the corresponding gene expression level...
February 16, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28329838/neighborhood-disadvantage-and-biological-aging-using-marginal-structural-models-to-assess-the-link-between-neighborhood-census-variables-and-epigenetic-aging
#20
Man-Kit Lei, Ronald L Simons, Steven R H Beach, Robert A Philibert
Objectives: Past research has reported an association between neighborhood disadvantage and healthy aging, but most of these studies utilize self-report measures of health or physical functioning and do not properly account for neighborhood selection effects, creating concerns regarding inflated associations. To overcome these limitations and provide a more stringent estimate of effects, the current study investigated the effect of neighborhood disadvantage on aging using newly developed epigenetic methods to assess rate of biological aging and marginal structural modeling (MSM) to account for potential confounds due to neighborhood selection...
March 3, 2017: Journals of Gerontology. Series B, Psychological Sciences and Social Sciences
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