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Factors underlying variable DNA methylation in a human community cohort

ABSTRACT: Epigenetics is emerging as an attractive mechanism to explain the persistent genomic embedding of early-life experiences. Tightly linked to chromatin, which packages DNA into chromosomes, epigenetic marks primarily serve to regulate the activity of genes. DNA methylation is the most accessible and characterized component of the many chromatin marks that constitute the epigenome, making it an ideal target for epigenetic studies in human populations. Here, using peripheral blood mononuclear cells collected from a community-based cohort stratified for early-life socioeconomic status, we measured DNA methylation in the promoter regions of more than 14,000 human genes. Using this approach, we broadly assessed and characterized epigenetic variation, identified some of the factors that sculpt the epigenome, and determined its functional relation to gene expression.We found that the leukocyte composition of peripheral blood covaried with patterns of DNA methylation at many sites, as did demographic factors, such as sex, age, and ethnicity. Furthermore, psychosocial factors, such as perceived stress, and cortisol output were associated with DNA methylation, as was early-life socioeconomic status. Interestingly, we determined that DNA methylation was strongly correlated to the ex vivo inflammatory response of peripheral blood mononuclear cells to stimulation with microbial products that engage Toll-like receptors. In contrast, our work found limited effects of DNA methylation marks on the expression of associated genes across individuals, suggesting a more complex relationship than anticipated

ORGANISM(S): Homo sapiens

PROVIDER: GSE37008 | GEO | 2012/10/10

SECONDARY ACCESSION(S): PRJNA158287

REPOSITORIES: GEO

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Factors underlying variable DNA methylation in a human community cohort

Project description:Epigenetics is emerging as an attractive mechanism to explain the persistent genomic embedding of early-life experiences. Tightly linked to chromatin, which packages DNA into chromosomes, epigenetic marks primarily serve to regulate the activity of genes. DNA methylation is the most accessible and characterized component of the many chromatin marks that constitute the epigenome, making it an ideal target for epigenetic studies in human populations. Here, using peripheral blood mononuclear cells collected from a community-based cohort stratified for early-life socioeconomic status, we measured DNA methylation in the promoter regions of more than 14,000 human genes. Using this approach, we broadly assessed and characterized epigenetic variation, identified some of the factors that sculpt the epigenome, and determined its functional relation to gene expression.We found that the leukocyte composition of peripheral blood covaried with patterns of DNA methylation at many sites, as did demographic factors, such as sex, age, and ethnicity. Furthermore, psychosocial factors, such as perceived stress, and cortisol output were associated with DNA methylation, as was early-life socioeconomic status. Interestingly, we determined that DNA methylation was strongly correlated to the ex vivo inflammatory response of peripheral blood mononuclear cells to stimulation with microbial products that engage Toll-like receptors. In contrast, our work found limited effects of DNA methylation marks on the expression of associated genes across individuals, suggesting a more complex relationship than anticipated This cohort consist of genomic DNA extracted from 94 PBMC DNA samples, bisulphite converted and hybridized, along with 5 technical replicates to the Illumina Infinium HumanMethylation27 Beadchip v1.2 for genome wide DNA methylation profiling.

2012-10-10 | E-GEOD-37008 | biostudies-arrayexpress

Widespread Discordance of DNA Methylation Between two Accessible Human Tissues

Project description:Inter-individual variability in DNA methylation has been hypothesized to contribute to complex phenotypes through epigenetic modulation of gene expression levels. Population epigenetic studies have been examining differences in DNA methylation in a variety of accessible tissues for association with specific diseases or exposures, but relatively little is known about how this inter-individual variation differs between tissues. This study presents an analysis of global DNA methylation differences between matched peripheral blood mononuclear cells and buccal epithelial cells; specifically it examines differential DNA methylation, probe-wise DNA methylation variance, and how methylation relates to a number of demographic factors across the two tissues. We found that peripheral blood mononuclear cells have overall higher DNA methylation than buccal epithelial cells, and regions of the genome that are differently methylated between the tissues tend to have low CpG density. We also discovered that although both tissues show extensive probe-wise variability, the specific regions and magnitude of variability differed between tissues. Finally, we observed that while both buccal epithelial and peripheral mononuclear blood cell DNA methylation was associated with gender, only methylation of the latter was associated with body mass index. The work presented here offers insight into variability of DNA methylation between individuals and across tissues and the suitability of buccal epithelial and peripheral mononuclear cells for the biological questions explored by epigenome-wide association studies in human populations. This cohort consist of genomic DNA extracted from the peripheral blood mononuclear cells and buccal epithelial cells of 25 individuals, bisulphite converted and hybridized to the Illumina GoldenGate Methylation Cancer Panel for genome wide DNA methylation profiling

2014-05-31 | E-GEOD-53396 | biostudies-arrayexpress

Widespread Discordance of DNA Methylation Between two Accessible Human Tissues

2014-05-31 | GSE53396 | GEO

DNA Methylation Changes and Childhood Asthma in the Inner City [gene expression]

Project description:Background: Epigenetic marks, like asthma, are heritable. They are influenced by the environment, direct the maturation of T cellslymphocytes, and have been shown to enhance the development of allergic airways disease in mice. Thus, we hypothesized that epigenetic marks are associated with allergic asthma in inner-city children. Methods: We compared methylation patterns and gene expression in inner-city children with persistent atopic asthma versus healthy controls, using DNA and RNA from peripheral blood mononuclear cells (PBMCs) from inner city children aged 6-12 years with persistent atopic asthma children and healthy controls. Results were externally validated with the GABRIELA study population. Results: Comparing asthmatics (N=97) to controls (N=97), we identified 81 regions that were differentially methylated. Several immune genes were hypomethylated in asthmatics, including IL-13, RUNX3, and a number of specific genes relevant to natural killer cells (KIR2DL4, KIR2DL3, KIR3DL1, and KLRD1) and T cells lymphocytes (TIGIT). 14 differentially methylated regions (DMRs) were associated with the serum IgE concentration of IgE, including RUNX3. These results were internally and externally validated with a global methylation assessment using a different methodology in our inner-city cohort and an independent European cohort (GABRIELA). Hypo- and hypermethylated genes tended to be associated with increased and decreased gene expression, respectively (P<0.6x10-11 for asthma and ; P<0.01 for IgE). To further explore the relationship between methylation and gene expression, we created a matrix of genomic changes in methylation versus transcriptional changes (methyl eQTL) for asthma, and identified cis- and trans-regulated genes whose expression was related to asthma asthma-associated methylation marks. peripheral blood mononuclear cells (PBMCs) from 97 atopic asthmatic and 97 nonatopic nonasthmatic children

2015-02-02 | E-GEOD-40732 | biostudies-arrayexpress

DNA Methylation Changes and Childhood Asthma in the Inner City [methylation]

2015-02-02 | E-GEOD-40576 | biostudies-arrayexpress

The epigenetic signature of systemic insulin resistance in obese women [BL]

Project description:Impaired ability of insulin to stimulate cellular glucose uptake and regulate metabolism, that is insulin resistance (IR), links adiposity to metabolic disorders such as type 2 diabetes (T2D), dyslipidemia and cardiovascular disease (Langenberg, 2012). Both genetic and epigenetic factors are implicated in development of systemic IR (Vaag, 2001). IR is characterized by elevated levels of fasting insulin in the general circulation. The aim of this study is to explore whether white adipose tissue (WAT) epigenetic dysregulation is associated with systemic IR by global CpG methylation and gene expression profiling in subcutaneous and visceral adipose tissue. A secondary aim is to determine whether the DNA methylation signature in peripheral blood mononuclear cells reflect WAT methylation, and can be used as marker for systemic IR. DNA methylation was analyzed in DNA extracted from SAT (subcutaneous adipose tissue) and VAT (visceral adipose tissue) pieces, as well as PBMCs (peripheral blood mononuclear cells), using the Infinium Human Methylation 450 BeadChip assay. This data is from PBMCs.

2016-08-01 | E-GEOD-76285 | biostudies-arrayexpress

The epigenetic signature of systemic insulin resistance in obese women [SC]

2016-08-01 | E-GEOD-76398 | biostudies-arrayexpress

The epigenetic signature of systemic insulin resistance in obese women [OM]

2016-08-01 | E-GEOD-76394 | biostudies-arrayexpress

Plasmodium falciparum S-adenosylmethionine synthetase is essential for parasite survival through a complex interaction network with cytoplasmic and nuclear proteins

Project description:Life-cycle progression of the human malaria parasite Plasmodium falciparum in the human and mosquito hosts requires epigenetic mechanisms to regulate the stage-dependency of gene expression, including DNA and histone methylation. Methylation reactions require S-adenosylmethionine (SAM), a universal biological methyl donor whose synthesis is catalyzed by the enzyme S-adenosylmethionine synthetase (SAMS). In P. falciparum, PfSAMS is encoded by a single gene and has been suggested to be crucial for malaria pathogenesis and transmission; however, to date PfSAMS has not been fully characterized. To gain deeper insight into the function of PfSAMS, we generated a conditional gene knockdown (KD) using the pSLI-glmS system. We show that PfSAMS is expressed in the cytosol and nucleus of blood stage parasites. PfSAMS-KD results in reduced histone methylation marks and leads to impaired intraerythrocytic growth and gametocyte development. To further determine the interaction network of PfSAMS we performed BioID analyses. We identified 664 nuclear and 213 cytosolic interactors linked to biological processes like transcriptional and cell cycle regulation. Our interaction data further unveil PfSAMS-specific interaction clusters of proteins involved in DNA replication, transcription and translation as well as proteostasis. Our findings emphasize the key roles of PfSAMS during intraerythrocytic growth and sexual stage development.

2022-07-13 | PXD034111 | JPOST Repository

Transcription profiling of human peripheral blood CD2+ leukocytes from PATH particpants

Project description:Gene expression profiling was carried out on peripheral blood CD2+ leukocytes from 29 children with asthma. The primary research question is whether gene expression differs in individuals from high socioeconomic status environments vs low socioeconomic status environments. Experiment Overall Design: Gene expression profiling was carried out on peripheral blood CD2+ leukocytes from 29 children with asthma. The primary research question is whether gene expression differs in individuals from high socioeconomic status environments vs low socioeconomic status environments.

2009-06-01 | E-GEOD-7894 | biostudies-arrayexpress

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