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Methylomics

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https://www.readbyqxmd.com/read/29330124/manipulating-the-epigenome-for-the-treatment-of-disorders-with-thrombotic-complications
#1
REVIEW
Faith A A Kwa, Denise E Jackson
The haemostatic system is tightly regulated to maintain homeostasis to avoid unwanted bleeding or thrombotic complications. Recent research has highlighted the importance of epigenetic changes, such as DNA methylation, histone modifications, and miRNA-based mechanisms, that alter gene expression. This can give rise to dysregulated haemostatic or vascular expressed molecules contributing to the development of thrombotic complications. Targeting these epigenetic changes could provide a new avenue for the treatment of pathological blood clots...
January 9, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29326313/dna-methylation-and-age-independent-cardiovascular-risk-an-epigenome-wide-approach-the-regicor-registre-giron%C3%A3-del-cor-study
#2
Alba Fernández-Sanlés, Sergi Sayols-Baixeras, Santiago Curcio, Isaac Subirana, Jaume Marrugat, Roberto Elosua
OBJECTIVE: The objectives of this study were to decipher whether age-independent cardiovascular risk is associated with DNA methylation at 5'-cytosine-phosphate-guanine-3' (CpG) level and to determine whether these differential methylation signatures are associated with the incidence of cardiovascular events. APPROACH AND RESULTS: We designed a 2-stage, cross-sectional, epigenome-wide association study. Age-independent cardiovascular risk calculation was based on vascular age and on the residuals of the relationship between age and cardiovascular risk...
January 11, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29326230/base-resolution-analysis-of-dna-methylation-patterns-downstream-of-dnmt3a-in-mouse-na%C3%A3-ve-b-cells
#3
Christopher G Duncan, Hrisavgi D Kondilis-Mangum, Sara A Grimm, Pierre R Bushel, Kaliopi Chrysovergis, John D Roberts, Frederick L Tyson, B Alex Merrick, Paul A Wade
The DNA methyltransferase, Dnmt3a, is dynamically regulated throughout mammalian B cell development and upon activation by antigenic stimulation. Dnmt3a inactivation in hematopoietic stem cells has been shown to drive B cell-related malignancies, including chronic lymphocytic leukemia (CLL), and associates with specific DNA methylation patterns in transformed cells. However, while it is clear that inactivation of Dnmt3a in hematopoietic stem cells has profound functional impacts, the consequences of Dnmt3a inactivation in cells of the B lineage are unclear...
January 11, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29317751/methylation-in-mycobacterium-tuberculosis-is-lineage-specific-with-associated-mutations-present-globally
#4
Jody Phelan, Paola Florez de Sessions, Leopold Tientcheu, Joao Perdigao, Diana Machado, Rumina Hasan, Zahra Hasan, Indra L Bergval, Richard Anthony, Ruth McNerney, Martin Antonio, Isabel Portugal, Miguel Viveiros, Susana Campino, Martin L Hibberd, Taane G Clark
DNA methylation is an epigenetic modification of the genome involved in regulating crucial cellular processes, including transcription and chromosome stability. Advances in PacBio sequencing technologies can be used to robustly reveal methylation sites. The methylome of the Mycobacterium tuberculosis complex is poorly understood but may be involved in virulence, hypoxic survival and the emergence of drug resistance. In the most extensive study to date, we characterise the methylome across the 4 major lineages of M...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317599/dna-methylome-variation-in-a-perinatal-nurse-visitation-program-that-reduces-child-maltreatment-a-27-year-follow-up
#5
Kieran J O'Donnell, Li Chen, Julia L MacIsaac, Lisa M McEwen, Thao Nguyen, Katherine Beckmann, Yuecai Zhu, Lawrence Ming Chen, Jeanne Brooks-Gunn, David Goldman, Elena L Grigorenko, James F Leckman, Josie Diorio, Neerja Karnani, David L Olds, Joanna D Holbrook, Michael S Kobor, Michael J Meaney
This study reveals the influence of child maltreatment on DNA methylation across the genome and provides the first evidence that a psychosocial intervention program, the Nurse Family Partnership (NFP), which targets mothers at risk for abusive parenting, associates with variation in the DNA methylome in adult offspring. The 188 participants were born to women randomly assigned to control (n = 99) or nurse-visited intervention groups (n = 89) and provided blood samples and a diagnostic interview at age 27 years...
January 10, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29304755/computational-approach-to-discriminate-human-and-mouse-sequences-in-patient-derived-tumour-xenografts
#6
Maurizio Callari, Ankita Sati Batra, Rajbir Nath Batra, Stephen-John Sammut, Wendy Greenwood, Harry Clifford, Colin Hercus, Suet-Feung Chin, Alejandra Bruna, Oscar M Rueda, Carlos Caldas
BACKGROUND: Patient-Derived Tumour Xenografts (PDTXs) have emerged as the pre-clinical models that best represent clinical tumour diversity and intra-tumour heterogeneity. The molecular characterization of PDTXs using High-Throughput Sequencing (HTS) is essential; however, the presence of mouse stroma is challenging for HTS data analysis. Indeed, the high homology between the two genomes results in a proportion of mouse reads being mapped as human. RESULTS: In this study we generated Whole Exome Sequencing (WES), Reduced Representation Bisulfite Sequencing (RRBS) and RNA sequencing (RNA-seq) data from samples with known mixtures of mouse and human DNA or RNA and from a cohort of human breast cancers and their derived PDTXs...
January 5, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29298815/genome-wide-characterisation-of-dna-methylation-in-an-invasive-lepidopteran-pest-the-cotton-bollworm-helicoverpa-armigera
#7
Christopher M Jones, Ka S Lim, Jason W Chapman, Chris Bass
The genes and genomes of insect pests are shaped by the wide array of selective forces encountered in their environments. While the molecular adaptations that evolve are beginning to be understood at the genomic and transcriptomic level they have been less well characterised at an epigenetic level. Here, we present a genome-wide map of DNA methylation, at single-nucleotide resolution for the cotton bollworm moth, Helicoverpa armigera; a globally invasive pest of agriculture. We show that methylation is almost identical in the larvae and adults of H...
January 3, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29297298/2d-em-clustering-approach-for-high-dimensional-data-through-folding-feature-vectors
#8
Alok Sharma, Piotr J Kamola, Tatsuhiko Tsunoda
BACKGROUND: Clustering methods are becoming widely utilized in biomedical research where the volume and complexity of data is rapidly increasing. Unsupervised clustering of patient information can reveal distinct phenotype groups with different underlying mechanism, risk prognosis and treatment response. However, biological datasets are usually characterized by a combination of low sample number and very high dimensionality, something that is not adequately addressed by current algorithms...
December 28, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29296817/runx1-regulates-site-specificity-of-dna-demethylation-by-recruitment-of-dna-demethylation-machineries-in-hematopoietic-cells
#9
Takahiro Suzuki, Yuri Shimizu, Erina Furuhata, Shiori Maeda, Mami Kishima, Hajime Nishimura, Saaya Enomoto, Yoshihide Hayashizaki, Harukazu Suzuki
RUNX1 is an essential master transcription factor in hematopoietic development and plays important roles in immune functions. Although the gene regulatory mechanism of RUNX1 has been characterized extensively, the epigenetic role of RUNX1 remains unclear. Here, we demonstrate that RUNX1 contributes DNA demethylation in a binding site-directed manner in human hematopoietic cells. Overexpression analysis of RUNX1 showed the RUNX1-binding site-directed DNA demethylation. The RUNX1-mediated DNA demethylation was also observed in DNA replication-arrested cells, suggesting an involvement of active demethylation mechanism...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295990/obligatory-and-facilitative-allelic-variation-in-the-dna-methylome-within-common-disease-associated-loci
#10
Christopher G Bell, Fei Gao, Wei Yuan, Leonie Roos, Richard J Acton, Yudong Xia, Jordana Bell, Kirsten Ward, Massimo Mangino, Pirro G Hysi, Jun Wang, Timothy D Spector
Integrating epigenetic data with genome-wide association study (GWAS) results can reveal disease mechanisms. The genome sequence itself also shapes the epigenome, with CpG density and transcription factor binding sites (TFBSs) strongly encoding the DNA methylome. Therefore, genetic polymorphism impacts on the observed epigenome. Furthermore, large genetic variants alter epigenetic signal dosage. Here, we identify DNA methylation variability between GWAS-SNP risk and non-risk haplotypes. In three subsets comprising 3128 MeDIP-seq peripheral-blood DNA methylomes, we find 7173 consistent and functionally enriched Differentially Methylated Regions...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29290793/epigenomic-characterization-of-a-p53-regulated-3p22-2-tumor-suppressor-that-inhibits-stat3-phosphorylation-via-protein-docking-and-is-frequently-methylated-in-esophageal-and-other-carcinomas
#11
Lili Li, Juan Xu, Guohua Qiu, Jianming Ying, Zhenfang Du, Tingxiu Xiang, Kai Yau Wong, Gopesh Srivastava, Xiao-Feng Zhu, Tony S Mok, Anthony Tc Chan, Francis Kl Chan, Richard F Ambinder, Qian Tao
Rationale: Oncogenic STAT3 signaling activation and 3p22-21.3 locus alteration are common in multiple tumors, especially carcinomas of the nasopharynx, esophagus and lung. Whether these two events are linked remains unclear. Our CpG methylome analysis identified a 3p22.2 gene, DLEC1, as a methylated target in esophageal squamous cell (ESCC), nasopharyngeal (NPC) and lung carcinomas. Thus, we further characterized its epigenetic abnormalities and functions. Methods: CpG methylomes were established by methylated DNA immunoprecipitation...
2018: Theranostics
https://www.readbyqxmd.com/read/29278425/genomic-perturbations-reveal-distinct-regulatory-networks-in-intrahepatic-cholangiocarcinoma
#12
Chirag Nepal, Colm J O'Rourke, Douglas Vnp Oliveira, Andrzej Taranta, Steven Shema, Prson Gautam, Julien Calderaro, Andrew Barbour, Chiara Raggi, Krister Wennerberg, Xin W Wang, Anja Lautem, Lewis R Roberts, Jesper B Andersen
Intrahepatic cholangiocarcinoma (iCCA) remains a highly heterogeneous malignancy that has eluded effective patient stratification to date. The extent to which such heterogeneity can be influenced by individual driver mutations remains to be evaluated. Here, we analyzed genomic (whole-exome sequencing, targeted exome sequencing) and epigenomic data from 496 patients, and used the three most recurrently mutated genes to stratify patients (IDH, KRAS, TP53, 'undetermined'). Using this molecular dissection approach, each subgroup was determined to possess unique mutational signature preferences, co-mutation profiles and enriched pathways...
December 26, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29273273/utility-of-dna-methylation-to-assess-placental-health
#13
Samantha L Wilson, Wendy P Robinson
DNA methylation (DNAm), a mitotically stable epigenetic mark, can influence as well as reflect gene expression. DNAm has been gaining interest for use as a biomarker for many conditions including placental insufficiency, specifically preeclampsia (PE) and intrauterine growth restriction (IUGR). Additionally, DNAm may retain a "memory" of earlier in utero exposures and hence provide insight into pathogeneses occurring earlier in gestation. This review will discuss the placental DNA methylome, the uses of DNAm to assess placental health, and considerations and limitations to understand in epigenome-wide association studies (EWAS)...
December 14, 2017: Placenta
https://www.readbyqxmd.com/read/29259247/ras-pathway-mutation-patterns-define-epigenetic-subclasses-in-juvenile-myelomonocytic-leukemia
#14
Daniel B Lipka, Tania Witte, Reka Toth, Jing Yang, Manuel Wiesenfarth, Peter Nöllke, Alexandra Fischer, David Brocks, Zuguang Gu, Jeongbin Park, Brigitte Strahm, Marcin Wlodarski, Ayami Yoshimi, Rainer Claus, Michael Lübbert, Hauke Busch, Melanie Boerries, Mark Hartmann, Maximilian Schönung, Umut Kilik, Jens Langstein, Justyna A Wierzbinska, Caroline Pabst, Swati Garg, Albert Catalá, Barbara De Moerloose, Michael Dworzak, Henrik Hasle, Franco Locatelli, Riccardo Masetti, Markus Schmugge, Owen Smith, Jan Stary, Marek Ussowicz, Marry M van den Heuvel-Eibrink, Yassen Assenov, Matthias Schlesner, Charlotte Niemeyer, Christian Flotho, Christoph Plass
Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome...
December 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29259021/evolutionary-expansion-of-dna-hypomethylation-in-the-mammalian-germline-genome
#15
Jianghan Qu, Emily Hodges, Antoine Molaro, Pascal Gagneux, Matthew D Dean, Gregory J Hannon, Andrew D Smith
DNA methylation in the germline is among the most important factors influencing the evolution of mammalian genomes. Yet little is known about its evolutionary rate or the fraction of the methylome that has undergone change. We compared whole-genome, single-CpG DNA methylation profiles in sperm of seven species: human, chimpanzee, gorilla, rhesus macaque, mouse, rat and dog, to investigate epigenomic evolution. We developed a phylo-epigenetic model for DNA methylation that accommodates the correlation of states at neighboring sites and allows for inference of ancestral states...
December 19, 2017: Genome Research
https://www.readbyqxmd.com/read/29258833/a-reference-genome-and-methylome-for-the-plasmodium-knowlesi-a1-h-1-line
#16
Ernest Diez Benavente, Paola Florez de Sessions, Robert W Moon, Munira Grainger, Anthony A Holder, Michael J Blackman, Cally Roper, Christopher J Drakeley, Arnab Pain, Colin J Sutherland, Martin L Hibberd, Susana Campino, Taane G Clark
Plasmodium knowlesi, a common parasite of macaques, is recognised as a significant cause of human malaria in Malaysia. The P. knowlesi A1H1 line has been adapted to continuous culture in human erythrocytes, successfully providing an in vitro model to study the parasite. We have assembled a reference genome for the PkA1-H.1 line using PacBio long read combined with Illumina short read sequence data. Compared with the H-strain reference, the new reference has improved genome coverage and a novel description of methylation sites...
December 16, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/29248544/genome-wide-dna-methylation-analysis-in-systemic-sclerosis-reveals-hypomethylation-of-interferon-associated-genes-in-cd4-and-cd8-t-cells
#17
Weifeng Ding, Weilin Pu, Lei Wang, Shuai Jiang, Xiaodong Zhou, Wenzhen Tu, Ling Yu, Jiaqian Zhang, Shicheng Guo, Qingmei Liu, Yanyun Ma, Sidi Chen, Wenyu Wu, John Reveille, Hejian Zou, Li Jin, Jiucun Wang
Epigenetic modifications, including DNA methylation, play an important role in the pathogenesis of autoimmune diseases. In this study, we characterized the DNA methylome in primary T cells of patients with systemic sclerosis (SSc). Genome-wide DNA methylation assays of CD4+ and CD8+ T cells from 24 SSc patients and 24 matched controls were conducted, and differentially methylated regions (DMRs) were validated. In the discovery stage, we found that hypomethylation of genes involved in the type I Interferon signaling pathway was significantly enriched in both CD4+ (p = 7...
December 14, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29242640/effects-of-maternal-obesity-on-wharton-s-jelly-mesenchymal-stromal-cells
#18
Heba Badraiq, Aleksandra Cvoro, Antonio Galleu, Marisa Simon, Cristian Miere, Carl Hobbs, Reiner Schulz, Richard Siow, Francesco Dazzi, Dusko Ilic
We investigated whether maternal metabolic environment affects mesenchymal stromal/stem cells (MSCs) from umbilical cord's Wharton's Jelly (WJ) on a molecular level, and potentially render them unsuitable for clinical use in multiple recipients. In this pilot study on umbilical cords post partum from healthy non-obese (BMI = 19-25; n = 7) and obese (BMI ≥ 30; n = 7) donors undergoing elective Cesarean section, we found that WJ MSC from obese donors showed slower population doubling and a stronger immunosuppressive activity...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29235922/dna-methylation-reprogramming-of-human-cancer-cells-by-expression-of-a-plant-5-methylcytosine-dna-glycosylase
#19
Teresa Morales-Ruiz, María Victoria García-Ortiz, Iván Devesa-Guerra, Laura Raya-Ruiz, Juan R Tejedor, Gustavo F Bayón, Marta I Sierra, Mario F Fraga, Rafael R Ariza, Teresa Roldán-Arjona
Patterns of DNA methylation, an important epigenetic modification involved in gene silencing and development, are disrupted in cancer cells. Understanding the functional significance of aberrant methylation in tumors remains challenging, due in part to the lack of suitable tools to actively modify methylation patterns. DNA demethylation caused by mammalian DNA methyltransferase inhibitors is transient and replication-dependent, whereas that induced by TET enzymes involves oxidized 5mC derivatives that perform poorly understood regulatory functions...
December 13, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29233839/genetics-of-tumors-of-the-adrenal-cortex
#20
Fidéline Bonnet-Serrano, Jerome Bertherat
This review describes the molecular alterations observed in the various types of tumors of the adrenal cortex, excluding Conn adenomas, especially the alterations identified by genomic approaches these last five years. Two main forms of bilateral adrenocortical tumors can be distinguished according to size and aspect of the nodules: primary pigmented nodular adrenal disease (PPNAD) which can be sporadic or part of Carney complex, and primary bilateral macro nodular adrenal hyperplasia (PBMAH). The bilateral nature of tumors suggests the existence of an underlying genetic predisposition...
December 12, 2017: Endocrine-related Cancer
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