Genome-wide analysis of DNA methylation patterns in horse

Background: DNA methylation is an epigenetic regulatory mechanism that plays an essential role in mediating biological processes and determining phenotypic plasticity in organisms. Although the horse reference genome and whole transcriptome data are publically available the global DNA methylation data are yet to be known. Results: We report the first genome-wide DNA methylation characteristics data from skeletal muscle, heart, lung, and cerebrum tissues of thoroughbred (TH) and Jeju (JH) horses, an indigenous Korea breed, respectively by methyl-DNA immunoprecipitation sequencing. The analysis of the DNA methylation patterns indicated that the average methylation density was the lowest in the promoter region, while the density in the coding DNA sequence region was the highest. Among repeat elements, a relatively high density of methylation was observed in long interspersed nuclear elements compared to short interspersed nuclear elements or long terminal repeat elements. We also successfully identified differential methylated regions through a comparative analysis of corresponding tissues from TH and JH, indicating that the gene body regions showed a high methylation density. Conclusions: We provide report the first DNA methylation landscape and differentially methylated genomic regions (DMRs) of thoroughbred and Jeju horses, providing comprehensive DMRs maps of the DNA methylome. These data are invaluable resource to better understanding of epigenetics in the horse providing information for the further biological function analyses.open1

Genome-Wide Analysis of DNA Methylation before- and after Exercise in the Thoroughbred Horse with MeDIP-Seq

Athletic performance is an important criteria used for the selection of superior horses. However, little is known about exercise-related epigenetic processes in the horse. DNA methylation is a key mechanism for regulating gene expression in response to environmental changes. We carried out comparative genomic analysis of genome-wide DNA methylation profiles in the blood samples of two different thoroughbred horses before and after exercise by methylated-DNA immunoprecipitation sequencing (MeDIP-Seq). Differentially methylated regions (DMRs) in the pre- and post-exercise blood samples of superior and inferior horses were identified. Exercise altered the methylation patterns. After 30 min of exercise, 596 genes were hypomethylated and 715 genes were hypermethylated in the superior horse, whereas in the inferior horse, 868 genes were hypomethylated and 794 genes were hypermethylated. These genes were analyzed based on gene ontology (GO) annotations and the exercise-related pathway patterns in the two horses were compared. After exercise, gene regions related to cell division and adhesion were hypermethylated in the superior horse, whereas regions related to cell signaling and transport were hypermethylated in the inferior horse. Analysis of the distribution of methylated CpG islands confirmed the hypomethylation in the gene-body methylation regions after exercise. The methylation patterns of transposable elements also changed after exercise. Long interspersed nuclear elements (LINEs) showed abundance of DMRs. Collectively, our results serve as a basis to study exercise-based reprogramming of epigenetic traitsclose

Rare Exonic Minisatellite Alleles in MUC2 Influence Susceptibility to Gastric Carcinoma

BACKGROUND: Mucins are the major components of mucus and their genes share a common, centrally-located region of sequence that encodes tandem repeats. Mucins are well known genes with respect to their specific expression levels; however, their genomic levels are unclear because of complex genomic properties. In this study, we identified eight novel minisatellites from the entire MUC2 region and investigated how allelic variation in these minisatellites may affect susceptibility to gastrointestinal cancer. METHODOLOGY/PRINCIPLE FINDINGS: We analyzed genomic DNA from the blood of normal healthy individuals and multi-generational family groups. Six of the eight minisatellites exhibited polymorphism and were transmitted meiotically in seven families, following Mendelian inheritance. Furthermore, a case-control study was performed that compared genomic DNA from 457 cancer-free controls with DNA from individuals with gastric (455), colon (192) and rectal (271) cancers. A statistically significant association was identified between rare exonic MUC2-MS6 alleles and the occurrence of gastric cancer: odds ratio (OR), 2.56; 95% confidence interval (CI), 1.31-5.04; and p = 0.0047. We focused on an association between rare alleles and gastric cancer. Rare alleles were divided into short (40, 43 and 44) and long (47, 50 and 54), according to their TR (tandem repeats) lengths. Interestingly, short rare alleles were associated with gastric cancer (OR = 5.6, 95% CI: 1.93-16.42; p = 0.00036). Moreover, hypervariable MUC2 minisatellites were analyzed in matched blood and cancer tissue from 28 patients with gastric cancer and in 4 cases of MUC2-MS2, minisatellites were found to have undergone rearrangement. CONCLUSIONS/SIGNIFICANCE: Our observations suggest that the short rare MUC2-MS6 alleles could function as identifiers for risk of gastric cancer. Additionally, we suggest that minisatellite instability might be associated with MUC2 function in cancer cells

A community resource for paired genomic and metabolomic data mining

Genomics and metabolomics are widely used to explore specialized metabolite diversity. The Paired Omics Data Platform is a community initiative to systematically document links between metabolome and (meta)genome data, aiding identification of natural product biosynthetic origins and metabolite structures.Peer reviewe

A Study for Health Hazard Evaluation of Methylene Chloride Evaporated from the Tear Gas Mixture

This study explored the health hazard of those exposed to methylene chloride by assessing its atmospheric concentration when a tear gas mixture was aerially dispersed. The concentration of methylene chloride ranged from 311.1–980.3 ppm (geometric mean 555.8 ppm), 30 seconds after the dispersion started. However, the concentration fell rapidly to below 10 ppm after dispersion was completed. The concentration during the dispersion did not surpass the National Institute for Occupational Safety and Health (NIOSH) 'immediately dangerous to life or health' value of 2,300 ppm, but did exceed the American Conference of Governmental Industrial Hygienists (ACGIH) excursion limit of 250 ppm. Since methylene chloride is highly volatile (vapor pressure, 349 mmHg at 20 °C), the post-dispersion atmospheric concentration can rise instantaneously. Moreover, the o-chlorobenzylidenemalononitril e formulation of tear gas (CS gas) is an acute upper respiratory tract irritant. Therefore, tear gas mixtures should be handled with delicate care

Identification of circulating endorepellin LG3 fragment: Potential use as a serological biomarker for breast cancer

Comparative proteome analysis was performed on the cultured media of human nontumor and malignant breast cell lines, Hs578Bst and Hs578T, respectively, in search of a serological biomarker(s) for breast cancer. Proteins in the conditioned media were separated by 2-D PAGE and then visualized by silver-staining. Eight proteins changed differentially by more than twofold were identified by MALDI-TOF/TOF MS. Among the proteins identified, the terminal laminin-like globular (LG3) domain of endorepellin, which was recently reported as an antiangiogenesis factor, was decreased in the cancer cell line. We confirmed the bone morphogenic protein-1 (BMP-1) mediated cleavage site on the N-terminus of endorepellin LG3 fragment. This finding suggests that the LG3 fragment is specifically released by a BMP-1 driven limited proteolytic process. The protein was also detected in plasma by Western blot analysis and selected reaction monitoring (SRM). The plasma level of the endorepellin LG3 fragment was significantly lower in breast cancer patients compared to healthy donors (p = 0.017; n = 12). The LG3 protein concentration in the control plasma was measured at approximately 3.7 pmol/mL compared to 1.8 pmol/mL in plasma from the cancer patients. We suggest that these results support the potential use of the endorepellin LG3 fragment as a new serological biomarker for breast cancer.N

Autoantibody to Tumor Antigen, Alpha 2-HS Glycoprotein: A Novel Biomarker of Breast Cancer Screening and Diagnosis

We sought to identify a new serum biomarker for breast cancer screening and diagnosis using stepwise proteomic analysis of sera from breast cancer patients to detect the presence of autoantibodies that react with urinary protein. Two-dimensional immunoblotting was done for screening autoimmunogenic tumor antigens in the urine of breast cancer patients. Reactive spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Among urinary proteins separated by two-dimensional electrophoresis, 13 spots showed strong reactivity with pooled sera from breast cancer patients or control sera. By mass spectrometry, we identified alpha 2-HS glycoprotein (AHSG) as a tumor antigen. Peripheral blood was obtained from 81 women diagnosed with breast cancer before surgery and 73 female donors without evidence of any malignancy for the individual analysis. In one-dimensional Western blot analysis, AHSG autoantibody was detected in 64 of 81 breast cancer patients (79.1%) and in 7 of 73 controls (9.6%). The sensitivity of this test in breast cancer patients was 79.0%. Our results suggest that AHSG and anti-AHSG autoantibody may be useful serum biomarkers for breast cancer screening and diagnosis.Chang JW, 2008, PROTEOM CLIN APPL, V2, P23, DOI 10.1002/prca.200780049Harris L, 2007, J CLIN ONCOL, V25, P5287, DOI 10.1200/JCO.2007.14.2364Caron M, 2007, MOL CELL PROTEOMICS, V6, P1115, DOI 10.1074/mcp.R600016-MCP200Hu S, 2006, PROTEOMICS, V6, P6326, DOI 10.1002/pmic.200600284Fujita Y, 2006, CLIN CANCER RES, V12, P6415, DOI 10.1158/1078-0432.CCR-06-1315Downes MR, 2006, BIOMARKERS, V11, P406, DOI 10.1080/13547500600799821Chang JW, 2005, FEBS LETT, V579, P2873, DOI 10.1016/j.febslet.2005.04.028Canelle L, 2005, J IMMUNOL METHODS, V299, P77, DOI 10.1016/j.jim.2005.01.015Molina R, 2005, TUMOR BIOL, V26, P281, DOI 10.1159/000089260Swallow CJ, 2004, CANCER RES, V64, P6402Carlsson L, 2004, J ANDROL, V25, P699Hong SH, 2004, CANCER RES, V64, P5504Hutchinson JN, 2004, CANCER RES, V64, P3171Pieper R, 2004, PROTEOMICS, V4, P1159, DOI 10.1002/pmic.200300661Mocellin S, 2003, BBA-REV CANCER, V1653, P61, DOI 10.1016/S0304-419X(03)00032-5Wilson KS, 2002, AM J PATHOL, V161, P1171Szweras M, 2002, J BIOL CHEM, V277, P19991, DOI 10.1074/jbc.M112234200Volkmann M, 2002, ONCOLOGY-BASEL, V63, P297, DOI 10.1159/000065472Sugi T, 2002, J REPROD IMMUNOL, V53, P269Le Naour F, 2001, CLIN CANCER RES, V7, P3328Brichory FM, 2001, P NATL ACAD SCI USA, V98, P9824Bosscher JR, 2001, GYNECOL ONCOL, V81, P138Gion M, 2001, EUR J CANCER, V37, P355Mathews ST, 2000, MOL CELL ENDOCRINOL, V164, P87Chen SH, 2000, FASEB J, V14, P565Menard S, 2000, J CELL PHYSIOL, V182, P150METCALFE S, 2000, BREAST CANCER RES, V2, P438Duffy MJ, 1999, ANN CLIN BIOCHEM, V36, P579Lenner P, 1999, BRIT J CANCER, V79, P927Wang HC, 1998, P NATL ACAD SCI USA, V95, P14429Molina R, 1998, BREAST CANCER RES TR, V51, P109Conroy SE, 1998, EUR J CANCER, V34, P942Disis ML, 1997, J CLIN ONCOL, V15, P3363Disis ML, 1997, ADV CANCER RES, V71, P343Chu KC, 1996, J NATL CANCER I, V88, P1571Bast RC, 1996, J CLIN ONCOL, V14, P2843vonMensdorffPouilly S, 1996, EUR J CANCER, V32A, P1325vanDalen A, 1996, ANTICANCER RES, V16, P2345MADIGAN MP, 1995, J NATL CANCER I, V87, P1681GOUREVITCH MM, 1995, BRIT J CANCER, V72, P934SRINIVAS PR, 1993, MOL ENDOCRINOL, V7, P1445JAMEEL A, 1992, INT J CANCER, V50, P409DNISTRIAN AM, 1991, TUMOR BIOL, V12, P82VANDALEN A, 1990, TUMOR BIOL, V11, P189TABAR L, 1985, LANCET, V1, P829ANDERSON L, 1977, P NATL ACAD SCI USA, V74, P54211

Size-Controlled Nanoparticle-Guided Assembly of Block Copolymers for Convex Lens-Shaped Particles

The tuning of interfacial properties at selective and desired locations on the particles is of great importance to create the novel structured particles by breaking the symmetry of their surface property. Herein, a dramatic transition of both the external shape and internal morphology of the particles of polystyrene-<i>b</i>-poly­(4-vinylpyridine) (PS-<i>b</i>-P4VP) was induced by precise positioning of size-controlled Au nanoparticle surfactants (Au NPs). The size-dependent assembly of the Au NPs was localized preferentially at the interface between the P4VP domain at the particle surface and the surrounding water, which generated a balanced interfacial interaction between two different PS/P4VP domains of the BCP particles and water, producing unique convex lens-shaped BCP particles. In addition, the neutralized interfacial interaction, in combination with the directionality of the solvent-induced ordering of the BCP domains from the interface of the particle/water, generated defect-free, vertically ordered porous channels within the particles. The mechanism for the formation of these novel nanostructures was investigated systemically by varying the size and the volume fraction of the Au NPs. Furthermore, these convex lens-shaped particles with highly ordered channels can be used as a microlens, in which the light can be concentrated toward the focal point with enhanced near-field signals. And, these particles can possess additional optical properties such as unique distribution of light scattering as a result of the well-ordered Au cylinders that filled into the channels, which hold great promise for use in optical, biological-sensing, and imaging applications

Size-Controlled Nanoparticle-Guided Assembly of Block Copolymers for Convex Lens-Shaped Particles

The tuning of interfacial properties at selective and desired locations on the particles is of great importance to create the novel structured particles by breaking the symmetry of their surface property. Herein, a dramatic transition of both the external shape and internal morphology of the particles of polystyrene-<i>b</i>-poly­(4-vinylpyridine) (PS-<i>b</i>-P4VP) was induced by precise positioning of size-controlled Au nanoparticle surfactants (Au NPs). The size-dependent assembly of the Au NPs was localized preferentially at the interface between the P4VP domain at the particle surface and the surrounding water, which generated a balanced interfacial interaction between two different PS/P4VP domains of the BCP particles and water, producing unique convex lens-shaped BCP particles. In addition, the neutralized interfacial interaction, in combination with the directionality of the solvent-induced ordering of the BCP domains from the interface of the particle/water, generated defect-free, vertically ordered porous channels within the particles. The mechanism for the formation of these novel nanostructures was investigated systemically by varying the size and the volume fraction of the Au NPs. Furthermore, these convex lens-shaped particles with highly ordered channels can be used as a microlens, in which the light can be concentrated toward the focal point with enhanced near-field signals. And, these particles can possess additional optical properties such as unique distribution of light scattering as a result of the well-ordered Au cylinders that filled into the channels, which hold great promise for use in optical, biological-sensing, and imaging applications