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Ivana V Yang, Brent S Pedersen, Andrew H Liu, George T O'Connor, Dinesh Pillai, Meyer Kattan, Rana Tawil Misiak, Rebecca Gruchalla, Stanley J Szefler, Gurjit K Khurana Hershey, Carolyn Kercsmar, Adam Richards, Allen D Stevens, Christena A Kolakowski, Melanie Makhija, Christine A Sorkness, Rebecca Z Krouse, Cynthia Visness, Elizabeth J Davidson, Corinne E Hennessy, Richard J Martin, Alkis Togias, William W Busse, David A Schwartz
BACKGROUND: Given the strong environmental influence on both epigenetic marks and allergic asthma in children, the epigenetic alterations in respiratory epithelia might provide insight into allergic asthma. OBJECTIVE: We sought to identify DNA methylation and gene expression changes associated with childhood allergic persistent asthma. METHODS: We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma (n = 36) versus healthy control subjects (n = 36)...
October 13, 2016: Journal of Allergy and Clinical Immunology
Rong Wang, Robert W van Leeuwen, Aniek Boers, Harry G Klip, Tim de Meyer, Renske D M Steenbergen, Wim van Criekinge, Ate G J van der Zee, Ed Schuuring, G Bea A Wisman
BACKGROUND: Cytology-based screening methods for cervical adenocarcinoma (ADC) and to a lesser extent squamous-cell carcinoma (SCC) suffer from low sensitivity. DNA hypermethylation analysis in cervical scrapings may improve detection of SCC, but few methylation markers have been described for ADC. We aimed to identify novel methylation markers for the early detection of both ADC and SCC. RESULTS: Genome-wide methylation profiling for 20 normal cervices, 6 ADC and 6 SCC using MethylCap-seq yielded 53 candidate regions hypermethylated in both ADC and SCC...
October 12, 2016: Oncotarget
Xin Li, Yun Liu, Tal Salz, Kasper D Hansen, Andrew P Feinberg
DNA methylation at the 5-postion of cytosine (5mC) is an epigenetic modification that regulates gene expression and cellular plasticity in development and disease. The ten-eleven translocation (TET) gene family oxidizes 5mC to 5-hydroxymethylcytosine (5hmC), providing an active mechanism for DNA demethylation, and may also provide its own regulatory function. Here we applied oxidative bisulfite sequencing to generate whole-genome DNA methylation and hydroxymethylation maps at single-base resolution in paired human liver and lung normal and cancer...
October 13, 2016: Genome Research
Ruth Pidsley, Elena Zotenko, Timothy J Peters, Mitchell G Lawrence, Gail P Risbridger, Peter Molloy, Susan Van Djik, Beverly Muhlhausler, Clare Stirzaker, Susan J Clark
BACKGROUND: In recent years the Illumina HumanMethylation450 (HM450) BeadChip has provided a user-friendly platform to profile DNA methylation in human samples. However, HM450 lacked coverage of distal regulatory elements. Illumina have now released the MethylationEPIC (EPIC) BeadChip, with new content specifically designed to target these regions. We have used HM450 and whole-genome bisulphite sequencing (WGBS) to perform a critical evaluation of the new EPIC array platform. RESULTS: EPIC covers over 850,000 CpG sites, including >90 % of the CpGs from the HM450 and an additional 413,743 CpGs...
October 7, 2016: Genome Biology
Bong-Seok Jo, In-Uk Koh, Jae-Bum Bae, Ho-Yeong Yu, Eun-Seok Jeon, Hae-Young Lee, Jae-Joong Kim, Murim Choi, Sun Shim Choi
Alterations in DNA methylation and gene expression have been implicated in the development of human dilated cardiomyopathy (DCM). Differentially methylated probes (DMPs) and differentially expressed genes (DEGs) were identified between the left ventricle (LV, a pathological locus for DCM) and the right ventricle (RV, a proxy for normal hearts). The data in this DiB are for supporting our report entitled "Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy" (Bong-Seok Jo, In-Uk Koh, Jae-Bum Bae, Ho-Yeong Yu, Eun-Seok Jeon, Hae-Young Lee, Jae-Joong Kim, Murim Choi, Sun Shim Choi, 2016) [1]...
December 2016: Data in Brief
Hisato Kobayashi, Tasuku Koike, Akihiko Sakashita, Keisuke Tanaka, Soichiro Kumamoto, Tomohiro Kono
Whole-genome shotgun bisulfite sequencing (WG-SBS) is currently the most powerful tool available for understanding genomewide cytosine methylation with single-base resolution; however, the high sequencing cost limits its widespread application, particularly for mammalian genomes. We mapped high- to low-coverage SBS short reads of mouse and human female developing germ cells to consensus sequences of repetitive elements that were multiplied in the respective host genome. This mapping strategy effectively identified active and evolutionarily young retrotransposon subfamilies and centromeric satellite repeats that were resistant to DNA demethylation during the investigated progressive stages of germ cell development...
October 3, 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Yen Ching Lim, Sook Yoong Chia, Shengnan Jin, Weiping Han, Chunming Ding, Lei Sun
OBJECTIVE: DNA methylation may be a stable epigenetic contributor to defining fat cell lineage. METHODS: We performed reduced representation bisulfite sequencing (RRBS) and RNA-seq to depict a genome-wide integrative view of the DNA methylome and transcriptome during brown and white adipogenesis. RESULTS: Our analysis demonstrated that DNA methylation is a stable epigenetic signature for brown and white cell lineage before, during, and after differentiation...
October 2016: Molecular Metabolism
Hamid Alinejad-Rokny, Firoz Anwar, Shafagh Waters, Miles P Davenport, Diako Ebrahimi
The dinucleotide CpG is highly underrepresented in the genome of human immunodeficiency virus type 1 (HIV-1). To identify the source of CpG depletion in the HIV-1 genome we investigated two biological mechanisms: a) CpG methylation-induced transcriptional silencing and b) CpG recognition by Toll-like receptors (TLRs). We hypothesized that HIV-1 has been under selective evolutionary pressure by these mechanisms leading to the reduction of CpG in its genome. A CpG depleted genome would enable HIV-1 to avoid methylation-induced transcriptional silencing and/or to avoid recognition by TLRs that identify foreign CpG sequences...
September 28, 2016: Molecular Biology and Evolution
Andrew D King, Kevin Huang, Liudmilla Rubbi, Shuo Liu, Cun-Yu Wang, Yinsheng Wang, Matteo Pellegrini, Guoping Fan
DNA methylation is one of a number of modes of epigenetic gene regulation. Here, we profile the DNA methylome, transcriptome, and global occupancy of histone modifications (H3K4me1, H3K4me3, H3K27me3, and H3K27ac) in a series of mouse embryonic stem cells (mESCs) with varying DNA methylation levels to study the effects of DNA methylation on deposition of histone modifications. We find that genome-wide DNA demethylation alters occupancy of histone modifications at both promoters and enhancers. This is reversed upon remethylation by Dnmt expression...
September 27, 2016: Cell Reports
Staci L Haney, Garland M Upchurch, Jana Opavska, David Klinkebiel, Adams Kusi Appiah, Lynette M Smith, Tayla B Heavican, Javeed Iqbal, Shantaram Joshi, Rene Opavsky
Cytosine methylation of DNA is an epigenetic modification involved in the repression of genes that affect biological processes including hematopoiesis. It is catalyzed by DNA methyltransferases, one of which -DNMT3A- is frequently mutated in human hematologic malignancies. We have previously reported that Dnmt3a inactivation in hematopoietic stem cells results in chronic lymphocytic leukemia (CLL) and CD8-positive peripheral T cell lymphomas (PTCL) in EμSRα-tTA;Teto-Cre;Dnmt3a(fl/fl); Rosa26LOXP(EGFP/EGFP) (Dnmt3a(Δ/Δ)) mice...
September 28, 2016: Scientific Reports
Mary Gehring
Schmitz and colleagues recently investigated DNA methylation patterns in diverse flowering plant species, finding substantial variation in the extent and distribution of methylation in angiosperms.Please see related Research article:
September 27, 2016: Genome Biology
Chad E Niederhuth, Adam J Bewick, Lexiang Ji, Magdy S Alabady, Kyung Do Kim, Qing Li, Nicholas A Rohr, Aditi Rambani, John M Burke, Joshua A Udall, Chiedozie Egesi, Jeremy Schmutz, Jane Grimwood, Scott A Jackson, Nathan M Springer, Robert J Schmitz
BACKGROUND: DNA methylation is an important feature of plant epigenomes, involved in the formation of heterochromatin and affecting gene expression. Extensive variation of DNA methylation patterns within a species has been uncovered from studies of natural variation. However, the extent to which DNA methylation varies between flowering plant species is still unclear. To understand the variation in genomic patterning of DNA methylation across flowering plant species, we compared single base resolution DNA methylomes of 34 diverse angiosperm species...
September 27, 2016: Genome Biology
Alvaro Muñoz-López, Damià Romero-Moya, Cristina Prieto, Verónica Ramos-Mejía, Antonio Agraz-Doblas, Ignacio Varela, Marcus Buschbeck, Anna Palau, Xonia Carvajal-Vergara, Alessandra Giorgetti, Anthony Ford, Majlinda Lako, Isabel Granada, Neus Ruiz-Xivillé, Sandra Rodríguez-Perales, Raul Torres-Ruíz, Ronald W Stam, Jose Luis Fuster, Mario F Fraga, Mahito Nakanishi, Gianni Cazzaniga, Michela Bardini, Isabel Cobo, Gustavo F Bayon, Agustin F Fernandez, Clara Bueno, Pablo Menendez
Induced pluripotent stem cells (iPSCs) are a powerful tool for disease modeling. They are routinely generated from healthy donors and patients from multiple cell types at different developmental stages. However, reprogramming leukemias is an extremely inefficient process. Few studies generated iPSCs from primary chronic myeloid leukemias, but iPSC generation from acute myeloid or lymphoid leukemias (ALL) has not been achieved. We attempted to generate iPSCs from different subtypes of B-ALL to address the developmental impact of leukemic fusion genes...
October 11, 2016: Stem Cell Reports
Christopher G Bell, Yudong Xia, Wei Yuan, Fei Gao, Kirsten Ward, Leonie Roos, Massimo Mangino, Pirro G Hysi, Jordana Bell, Jun Wang, Timothy D Spector
BACKGROUND: Advancing age progressively impacts on risk and severity of chronic disease. It also modifies the epigenome, with changes in DNA methylation, due to both random drift and variation within specific functional loci. RESULTS: In a discovery set of 2238 peripheral-blood genome-wide DNA methylomes aged 19-82 years, we identify 71 age-associated differentially methylated regions within the linkage disequilibrium blocks of the single nucleotide polymorphisms from the NIH genome-wide association study catalogue...
2016: Genome Biology
Kathleen R Stewart, Lenka Veselovska, Gavin Kelsey
Epigenetic modifications established during gametogenesis regulate transcription and other nuclear processes in gametes, but also have influences in the zygote, embryo and postnatal life. This is best understood for DNA methylation which, established at discrete regions of the oocyte and sperm genomes, governs genomic imprinting. In this review, we describe how imprinting has informed our understanding of de novo DNA methylation mechanisms, highlight how recent genome-wide profiling studies have provided unprecedented insights into establishment of the sperm and oocyte methylomes and consider the fate and function of gametic methylation and other epigenetic modifications after fertilization...
October 2016: Epigenomics
Charlotte Ling, Tina Rönn
Epigenetic variation in human adipose tissue has been linked to type 2 diabetes and its related risk factors including age and obesity. Insulin resistance, a key risk factor for type 2 diabetes, may also be associated with altered DNA methylation in visceral and subcutaneous adipose tissue. Furthermore, linking epigenetic variation in target tissues to similar changes in blood cells may identify new blood-based biomarkers. In this issue of Diabetologia, Arner et al studied the transcriptome and methylome in subcutaneous and visceral adipose tissue of 80 obese women who were either insulin-sensitive or -resistant (DOI 10...
November 2016: Diabetologia
Zhaobo Lang, Shaojun Xie, Jian-Kang Zhu
Intraspecific phenotypic diversity is controlled by natural genetic and epigenetic variation. Kawakatsu et al. recently sequenced the DNA methylomes of a global collection of over 1000 Arabidopsis accessions, and have thereby provided a comprehensive resource for studying natural genetic and epigenetic variation as well as the association of such variation with phenotypic diversity.
September 16, 2016: Trends in Plant Science
Chelsea R McCoy, Samir Rana, Sara Anne Stringfellow, Jeremy J Day, J Michael Wyss, Sarah M Clinton, Ilan A Kerman
Early-life stress (ELS) can alter neurodevelopment in variable ways, ranging from producing deleterious outcomes to stress resilience. While most ELS studies focus on its harmful effects, recent work by our laboratory and others shows that ELS elicits positive effects in certain individuals. We exposed Wistar Kyoto (WKY) rats, known for a stress reactive, anxiety/depression-like phenotype, to maternal separation (MS), a model of ELS. MS exposure elicited anxiolytic and antidepressant behavioral effects as well as improved cardiovascular function in adult WKY offspring...
September 19, 2016: European Journal of Neuroscience
Charlotte A M Cecil, Rebecca G Smith, Esther Walton, Jonathan Mill, Eamon J McCrory, Essi Viding
Childhood maltreatment is a key risk factor for poor mental and physical health. Recently, variation in epigenetic processes, such as DNA methylation, has emerged as a potential pathway mediating this association; yet, the extent to which different forms of maltreatment may be characterized by unique vs shared epigenetic signatures is currently unknown. In this study, we quantified DNA methylation across the genome in buccal epithelial cell samples from a high-risk sample of inner-city youth (n = 124; age = 16-24; 53% female), 68% of whom reported experiencing at least one form of maltreatment while growing up...
September 13, 2016: Journal of Psychiatric Research
Kenjiro Shirane, Kazuki Kurimoto, Yukihiro Yabuta, Masashi Yamaji, Junko Satoh, Shinji Ito, Akira Watanabe, Katsuhiko Hayashi, Mitinori Saitou, Hiroyuki Sasaki
Specification of primordial germ cells (PGCs) activates epigenetic reprogramming for totipotency, the elucidation of which remains a fundamental challenge. Here, we uncover regulatory principles for DNA methylation reprogramming during in vitro PGC specification, in which mouse embryonic stem cells (ESCs) are induced into epiblast-like cells (EpiLCs) and then PGC-like cells (PGCLCs). While ESCs reorganize their methylome to form EpiLCs, PGCLCs essentially dilute the EpiLC methylome at constant, yet different, rates between unique sequence regions and repeats...
October 10, 2016: Developmental Cell
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