Whole-genome DNA methylation and expression profiles of CD4+ CD28+ and CD4+ CD28null T lymphocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE78942 | GEO | 2016/12/15
SECONDARY ACCESSION(S): PRJNA314472
REPOSITORIES: GEO
Similar Datasets
Project description:The loss of the CD28 co-stimulatory molecule by CD4+ lymphocytes (CD28null T cells) is accompanied by the acquisition of new biological and functional properties that lead to an impaired immune response. The regulatory mechanisms that govern the appearance and function of this cell subset in several inflammatory disorders and in healthy individuals, mainly in aging, are yet a controversial point. Here, we provide the whole-genome DNA methylation profile of CD28null T cells and its CD28+ counterpart. A comparative analysis reveals that 296 genes are differentially methylated between both cell subsets. One hundred sixty (160 genes) associated with the cytotoxicy ability (e.g., GRZB, TYROBP, and RUNX3) and cytokine/chemokine signaling (e.g., CX3CR1, CD27, and IL1R) are demetylated in CD28null T cells, whilst 136 de-novo methylated genes matched with defects in the TCR signaling pathway (e.g., ITK, TXK, CD3G, and LCK). Overall, our results reveal that CD28null T cells have a unique DNA methylation landscape, which is associated with alteration in gene expression and contributes to the functionality of these cells. Understanding these epigenetic regulatory mechanisms could provide novel therapeutic strategies to prevent the accumulation and activation of these cells in aging and inflammatory disorders.
2016-12-15 | GSE78940 | GEO
Project description:Aging is associated with a progressive loss of the CD28 costimulatory molecule in CD4+ lymphocytes (CD28null T cells), which is accompanied by the acquisition of new biological and functional properties that give rise to an impaired immune response. The regulatory mechanisms that govern the appearance and function of this cell subset during aging and in several associated inflammatory disorders remain controversial. Here, we present the whole-genome DNA methylation and gene expression profiles of CD28null T cells and its CD28+ counterpart. A comparative analysis revealed that 296 genes are differentially methylated between the two cell subsets. A total of 160 genes associated with cytotoxicity (e.g. GRZB, TYROBP, and RUNX3) and cytokine/chemokine signaling (e.g. CX3CR1, CD27, and IL-1R) are demethylated in CD28null T cells, while 136 de novo-methylated genes matched defects in the TCR signaling pathway (e.g. ITK, TXK, CD3G, and LCK). TCR-landscape analysis confirmed that CD28null T cells have an oligo/monoclonal expansion over the polyclonal background of CD28+ T cells, but feature a Vβ family repertoire specific to each individual. We reported that CD28null T cells show a preactivation state characterized by a higher level of expression of inflammasome-related genes that leads to the release of IL-1β when activated. Overall, our results demonstrate that CD28null T cells have a unique DNA methylation landscape, which is associated with differences in gene expression, contributing to the functionality of these cells. Understanding these epigenetic regulatory mechanisms could suggest novel therapeutic strategies to prevent the accumulation and activation of these cells during aging.
| S-EPMC5334526 | biostudies-literature
Project description:The loss of the CD28 co-stimulatory molecule by CD4+ lymphocytes (CD28null T cells) is accompanied by the acquisition of new biological and functional properties that lead to an impaired immune response. The regulatory mechanisms that govern the appearance and function of this cell subset in several inflammatory disorders and in healthy individuals, mainly in aging, are yet a controversial point. Here, we provide the whole-genome DNA methylation and gene expression profiles of CD28null T cells and its CD28+ counterpart. A comparative analysis reveals that 296 genes are differentially methylated between both cell subsets. One hundred sixty (160 genes) associated with the cytotoxicy ability (e.g., GRZB, TYROBP, and RUNX3) and cytokine/chemokine signaling (e.g., CX3CR1, CD27, and IL1R) are demetylated in CD28null T cells, whilst 136 de-novo methylated genes matched with defects in the TCR signaling pathway (e.g., ITK, TXK, CD3G, and LCK). Moreover, we show that genes related inflammasome activation are differentially expressed between CD28null and CD28+ T cells, highlight the contribution of this pathways to the pro-inflammatory profile of CD28null T cells. Overall, our results reveal that CD28null T cells have a unique DNA methylation landscape, which is associated with alteration in gene expression and contributes to the functionality of these cells. Understanding these epigenetic regulatory mechanisms could provide novel therapeutic strategies to prevent the accumulation and activation of these cells in aging and inflammatory disorders.
2016-12-15 | GSE78941 | GEO
Project description:Whole-genome DNA methylation and expression profiles of CD4+ CD28+ and CD4+ CD28null T lymphocytes
| PRJNA314472 | ENA
Project description:Innate lymphocytes encompass a diverse array of phenotypic identities with specialized functions. DNA methylation and hydroxymethylation are essential for epigenetic fidelity and fate commitment. The landscapes of these modifications are unknown in innate lymphocytes. Here, we characterized the whole-genome distribution of methyl-CpG and 5-hydroxymethylcytosine (5hmC) in mouse innate lymphoid cell 3 (ILC3), ILC2 and natural killer (NK) cells. We identified differentially methylated regions (DMRs) and differentially hydroxymethylated regions (DHMRs) between ILC and NK cell subsets and correlated them with transcriptional signatures. We associated lineage-determining transcription factors (LDTFs) with demethylation and demonstrated unique patterns of DNA methylation/hydroxymethylation in relationship to open chromatin regions (OCRs), histone modifications and TF-binding sites. We further identified an association between hydroxymethylation and NK cell superenhancers (SEs). Using mice lacking the DNA hydroxymethylase TET2, we showed the requirement for TET2 in optimal production of hallmark cytokines by ILC3s and interleukin-17A (IL-17A) by inflammatory ILC2s. These findings provide a powerful resource for studying innate lymphocyte epigenetic regulation and decode the regulatory logic governing their identity.
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Project description:DNA methylation plays critical roles in gene regulation and cellular specification without altering DNA sequences. The wide application of reduced representation bisulfite sequencing (RRBS) and whole genome bisulfite sequencing (bis-seq) opens the door to study DNA methylation at single CpG site resolution. One challenging question is how best to test for significant methylation differences between groups of biological samples in order to minimize false positive findings.We present a statistical analysis package, methylSig, to analyse genome-wide methylation differences between samples from different treatments or disease groups. MethylSig takes into account both read coverage and biological variation by utilizing a beta-binomial approach across biological samples for a CpG site or region, and identifies relevant differences in CpG methylation. It can also incorporate local information to improve group methylation level and/or variance estimation for experiments with small sample size. A permutation study based on data from enhanced RRBS samples shows that methylSig maintains a well-calibrated type-I error when the number of samples is three or more per group. Our simulations show that methylSig has higher sensitivity compared with several alternative methods. The use of methylSig is illustrated with a comparison of different subtypes of acute leukemia and normal bone marrow samples.methylSig is available as an R package at http://sartorlab.ccmb.med.umich.edu/software.Supplementary data are available at Bioinformatics online.
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Project description:Methylation of CpG dinucleotides is a fundamental mechanism of epigenetic regulation in eukaryotic genomes. Development of methods for rapid genome wide methylation profiling will greatly facilitate both hypothesis and discovery driven research in the field of epigenetics. In this regard, a single molecule approach to methylation profiling offers several unique advantages that include elimination of chemical DNA modification steps and PCR amplification.A single molecule approach is presented for the discernment of methylation profiles, based on optical mapping. We report results from a series of pilot studies demonstrating the capabilities of optical mapping as a platform for methylation profiling of whole genomes. Optical mapping was used to discern the methylation profile from both an engineered and wild type Escherichia coli. Furthermore, the methylation status of selected loci within the genome of human embryonic stem cells was profiled using optical mapping.The optical mapping platform effectively detects DNA methylation patterns. Due to single molecule detection, optical mapping offers significant advantages over other technologies. This advantage stems from obviation of DNA modification steps, such as bisulfite treatment, and the ability of the platform to assay repeat dense regions within mammalian genomes inaccessible to techniques using array-hybridization technologies.
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Project description: Not available
| S-DIXA-D-1150 | biostudies-other
Project description:Objective:This study aimed to comprehensively assess Epstein-Barr virus (EBV)-induced methylation alterations of B cell across whole genome. Methods:We compared DNA methylation patterns of primary B cells and corresponding lymphoblastoid cell lines (LCLs) from eight participants. The genome-wide DNA methylation profiles were compared at over 850,000 genome-wide methylation sites. Results:DNA methylation analysis revealed 87,732 differentially methylated CpG sites, representing approximately 12.41% of all sites in LCLs compared to primary B cells. The hypermethylated and hypomethylated CpG sites were about 22.75% or 77.25%, respectively. Only 0.8% of hypomethylated sites and 4.5% of hypermethylated sites were located in CpG islands, whereas 8.0% of hypomethylated sites and 16.3% of hypermethylated sites were located in shore (N_shore and S_shore). Using principal component analysis of the DNA methylation profiles, primary B cells and LCLs could be accurately predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differently methylated genes revealed that most of the top GO biological processes were related to cell activation and immune response, and some top enrichment pathways were related with activation and malignant transformation of human B cells. Conclusions:Our study demonstrated genome-wide DNA methylation variations between primary B cells and corresponding LCLs, which might yield new insight on the methylation mechanism of EBV-induced immortalization.
| S-EPMC5842224 | biostudies-literature
Project description:We investigated the change in DNA methylation in peripheral blood CD4+ lymphocytes over time, examined the relation between CD4+ lymphocytes and brain methylation, and compared their associations with AD pathology.Genome-wide methylation was measured three times in 41 older persons using Illumina Infinium HumanMethylation450 array. The two CD4+ lymphocytes measures were at study baseline and proximate to death. Brain tissue came from frozen dorsolateral prefrontal cortex.Global methylation features were conserved across tissue. At individual CpG sites, methylation level was concordant between the two CD4+ lymphocytes but more diffuse between CD4+ lymphocytes and brain. Previous associations of brain methylation with neuritic plaques at target methylation sites were not replicated in CD4+ lymphocytes.There is no strong evidence of change in CD4+ lymphocytes methylation among older persons over an average of 7.5 years. Methylation associations with AD pathology found in neocortex are not directly reflected in CD4+ lymphocytes.
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