Project description:Genome-wide DNA methylation reference profiles of CD4+ cells after CD3 and CD28 stimulation in two healthy human individuals using the MeDIP technique a custom oligonucleotide array targetting the vast majority of annotated TSSs and non-promoter CGIs in the human genome.
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.
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.
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.
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.
Project description:SPO11-promoted DNA double-strand breaks (DSBs) formation is a crucial step for meiotic recombination, and it is indispensable to detect the broken DNA ends accurately for dissecting the molecular mechanisms behind. Here, we report a novel technique, named DEtail-seq (DNA End tailing followed by sequencing), that can directly and quantitatively capture the meiotic DSB 3’ overhang hotspots at single-nucleotide resolution.