Tet2-mediated DNA demethylation controls T cell cytokine expression
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ABSTRACT:
PROVIDER: PRJNA213139 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR942506.fastq.gz | Fastqsanger.gz | |||
| SRR942507.fastq.gz | Fastqsanger.gz | |||
| SRR942508.fastq.gz | Fastqsanger.gz | |||
| SRR942509.fastq.gz | Fastqsanger.gz | |||
| SRR942510.fastq.gz | Fastqsanger.gz |
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Project description:T cell function is regulated by epigenetic mechanisms. 5-methylcytosine (5mC) conversion to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (Tet) proteins was identified to mediate DNA demethylation. Here, we characterize the genome-wide distribution of 5hmC in T cells using DNA immunoprecipitation coupled with high-throughput DNA sequencing. 5hmC marks signature genes associated with effector cell differentiation in the putative regulatory elements. Moreover, Tet2 protein is recruited to 5hmC-containing regions, dependent on lineage-specific transcription factors. Deletion of the Tet2 gene in T cells decreased their cytokine expression, associated with reduced p300 recruitment. In vivo, Tet2 plays a critical role in the expression of cytokine genes. Collectively, our findings for the first time demonstrate a key role of Tet-mediated active DNA demethylation in T cells. A total of 8 samples were analyzed. The expression patterns in Tet2 wild-type and deficient Th1 and Th17 cells were analyzed.
2015-04-12 | E-GEOD-66944 | biostudies-arrayexpress
Project description:The conversion of 5-methylcytosine (5mC) into 5-Hydroxymethylcytosine (5hmC) by ten-eleven translocation (Tet) family has recently been identified as a key process for active DNA demethylation, whose effects in the immune response is currently unknown. We used microarrays to characterize the regulation of Tet2 in T cells. We found that deletion of the Tet2 gene in T cells decreased expression of effector cytokines such as IFN-?, IL-17, and IL-10. To analyze the regulation of Tet2 in Th subset differentation, CD2(Cre)Tet2(f/f) mice were used to derive Tet2-deficient Th1 and Th17 cells, and Tet2(f/f) mice were used for Tet2-enriched Th1 and Th17 cells.
2015-04-12 | E-GEOD-48657 | biostudies-arrayexpress
Project description:The conversion of 5-methylcytosine (5mC) into 5-Hydroxymethylcytosine (5hmC) by ten-eleven translocation (Tet) family has recently been identified as a key process for active DNA demethylation, whose effects in the immune response is currently unknown. Examination of both 5mC and 5hmC modifications in 5 Th cell types. CD2(Cre)Tet2(f/f) mice (previously described in Moran-Crusio et al.,2011) and wild-type littermates on the mixed background were used in experiments.
2015-04-12 | E-GEOD-49139 | biostudies-arrayexpress
Project description:T cell function is regulated by epigenetic mechanisms. 5-methylcytosine (5mC) conversion to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (Tet) proteins was identified to mediate DNA demethylation. Here, we characterize the genome-wide distribution of 5hmC in T cells using DNA immunoprecipitation coupled with high-throughput DNA sequencing. 5hmC marks signature genes associated with effector cell differentiation in the putative regulatory elements. Moreover, Tet2 protein is recruited to 5hmC-containing regions, dependent on lineage-specific transcription factors. Deletion of the Tet2 gene in T cells decreased their cytokine expression, associated with reduced p300 recruitment. In vivo, Tet2 plays a critical role in the expression of cytokine genes. Collectively, our findings for the first time demonstrate a key role of Tet-mediated active DNA demethylation in T cells.
2015-04-12 | GSE66944 | GEO
Project description:T cell function is regulated by epigenetic mechanisms. 5-methylcytosine (5mC) conversion to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (Tet) proteins was identified to mediate DNA demethylation. Here, we characterize the genome-wide distribution of 5hmC in T cells using DNA immunoprecipitation coupled with high-throughput DNA sequencing. 5hmC marks signature genes associated with effector cell differentiation in the putative regulatory elements. Moreover, Tet2 protein is recruited to 5hmC-containing regions, dependent on lineage-specific transcription factors. Deletion of the Tet2 gene in T cells decreased their cytokine expression, associated with reduced p300 recruitment. In vivo, Tet2 plays a critical role in the expression of cytokine genes. Collectively, our findings for the first time demonstrate a key role of Tet-mediated active DNA demethylation in T cells.
2015-04-12 | GSE66268 | GEO
Project description:Regulation of T cell cytokine expression by Tet2-mediated DNA demethylation
| PRJNA278444 | ENA
Project description:The conversion of 5-methylcytosine (5mC) into 5-Hydroxymethylcytosine (5hmC) by ten-eleven translocation (Tet) family has recently been identified as a key process for active DNA demethylation, whose effects in the immune response is currently unknown. We used microarrays to characterize the regulation of Tet2 in T cells. We found that deletion of the Tet2 gene in T cells decreased expression of effector cytokines such as IFN-γ, IL-17, and IL-10.
2015-04-12 | GSE48657 | GEO
Project description:Host antiviral innate immune response is regulated by epigenetic mechanisms. TET2 oxidizes the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in a process that activates demethylation of CpG DNA. Here, we characterize the genome-wide distribution of 5hmC in both wild-type and TET2-knockout THP-1 cells infected with the influenza A virus (IAV) using DNA immunoprecipitation by anti-5hmc antibody coupled with high-throughput DNA sequencing. 5hmC marks signature genes associated with host innate immune response against IAV infection. Moreover, TET2 expression is inhibited by IAV infection via viral endoribonuclease PA-X . Deletion of the TET2 gene in THP-1 cells decreased expression of genes related to interferon signaling. We further verified that TET2 plays a critical role in the expression of STAT1 and some interferon-stimulated genes through demethylation. Collectively, our findings demonstrate a key role of TET2-mediated active DNA demethylation in anti-IAV immunity. Hydroxymethylated DNA immunoprecipitation-sequencing (hMeDIP-Seq) in IAV-infected wild-type and TET2-knockout THP-1 cells.
2023-07-13 | GSE223191 | GEO
Project description:The conversion of 5-methylcytosine (5mC) into 5-Hydroxymethylcytosine (5hmC) by ten-eleven translocation (Tet) family has recently been identified as a key process for active DNA demethylation, whose effects in the immune response is currently unknown.
2015-04-12 | GSE49139 | GEO
Project description:CD8 T cell memory differentiation endows T cells with an ability to rapidly induce effector functions upon pathogen re-encounter. While it is well established that substantial epigenetic remodeling occurs during the effector stage of the immune response, the signaling events that imprint CD8 T cells with these stable epigenetic programs are not well-defined. To gain insight into the signaling determinants of effector-associated epigenetic programming among CD8 T cells, we explored the role of IL-12 in the imprinting of IFNg expression during human CD8 T cell priming. We observe that anti-CD3/CD28-mediated stimulation of human naïve CD8 T cells is not sufficient to induce substantial demethylation of the IFNg promotor. However, anti-CD3/CD28 stimulation in the presence of the inflammatory cytokine, IL-12, resulted in significant and stable demethylation of the IFNg locus that was commensurate with an increase in IFNg expression. We further show that IL-12-associated demethylation of the IFNg locus is coupled to cell division through TET2-dependent demethylation in an ex vivo human CAR T cell model system and an in vivo immunologically competent murine system. Collectively, these data illustrate that IL-12 signaling promotes TET2-mediated effector epigenetic programming in CD8 T cells during the primary immune response and serve as proof of concept that signal 3 cytokines can be used to guide the induction of epigenetically regulated traits among T cells used for adoptive immunotherapies.
2021-08-31 | GSE182968 | GEO