Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA120635 | ENA |
REPOSITORIES: ENA
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Project description:Objective: Systemic lupus erythematosus (SLE) has limited monozygotic (MZ) twin concordance, implying a role for other pathogenic factors than genetic variation, such as epigenetic changes. Using the disease discordant twin model, we investigated genome-wide DNA methylation changes in sorted CD4+ T-cells, monocytes, granulocytes and B-cells in twin pairs with at least one SLE-affected twin. Methods: Peripheral blood from 15 SLE twin pairs (six MZ, nine dizygotic (DZ)) was processed using gradient density centrifugation for the granulocyte fraction. CD4+ T-cells, monocytes and B-cells were further isolated using magnetic beads. Genome-wide DNA methylation was analysed using Infinium HumanMethylation450K BeadChips. Probes with a p-value <0.01 between SLE twins and co-twins were considered statistically significant and a median DNA methylation difference >7% biologically relevant. Findings were validated using pyrosequencing and replicated in an independent case-control sample. Results: In paired analyses of discordant SLE twins restricted to the gene promoter and start region, we identified 55, 327, 247 and 1628 genes with differentially methylated CpGs in CD4+ T-cells, monocytes, granulocytes and B-cells, respectively. All cell types displayed marked hypomethylation in interferon-regulated genes, such as IFI44L, PARP9 and IFITM1, which was more pronounced in twins with flare within the past two years. In contrast to the other cell types, differentially methylated CpGs in B-cells were predominantly hypermethylated, where the most important upstream regulators included TNF and EP300. Conclusion: Hypomethylation of interferon-regulated genes occurs in all major cellular compartments in SLE twins. The observed B-cell promoter hypermethylation is a novel finding with potential significance for SLE pathogenesis.
2018-03-19 | GSE110607 | GEO
Project description:This is the first high-throughput analysis of DNA methylation in autoimmune diseases. We have used a cohort of MZ twins discordant for three diseases whose clinical signs often overlap: systemic lupus erythematosus (SLE), rheumatoid arthritis and dermatomyositis. Only MZ twins discordant for SLE featured widespread changes in the DNA methylation status of a significant number of genes. Individual analysis confirmed the existence of DNA methylation and expression changes in genes relevant to SLE pathogenesis. Our findings not only identify potentially relevant DNA methylation markers for the clinical characterization of SLE patients but also support the notion that epigenetic changes may be critical in the clinical manifestations of autoimmune disease. Total DNA isolated by standard procedures from 59 White Blood Cell (WBC) samples corresponding to monozygotic twins discordant for three different autoimmune diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and dermatomyositis (DM) and two additional controls for each MZ twin pair.
2009-11-16 | E-GEOD-19033 | biostudies-arrayexpress
Project description:Changes in DNA methylation pattern following intervention in PTSD patients
| PRJNA361512 | ENA
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
2011-08-25 | GSE23936 | GEO
Project description:Genome-wide DNA methylation pattern changes in basal-like breast cancer patients
| PRJNA394246 | ENA
Project description:Widespread Discordance of DNA Methylation Between two Accessible Human Tissues
| PRJNA231916 | ENA
Project description:DNA Methylation Across Monozygotic Twin Pairs and Their Parents
| PRJNA262568 | ENA
Project description:Many obesity-associated SNPs strongly associate with DNA methylation changes at proximal promoters and enhancers
| PRJNA296032 | ENA
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs. Two-condition experiment, KP MSCs vs. 3A6 MSCs.
2011-08-24 | E-GEOD-23936 | biostudies-arrayexpress
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature