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Transcription factors drive Tet2-mediated enhancer demethylation to reprogram cell fate

ABSTRACT: Transcription factors drive Tet2-mediated enhancer demethylation to reprogram cell fate

PROVIDER: PRJNA401421 | ENA |

REPOSITORIES: ENA

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Tet2-mediated DNA demethylation controls T cell cytokine expression [array]

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

Transcription factors drive Tet2-mediated enhancer demethylation to reprogram cell fate

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-01-31 | GSE103470 | GEO

Mus musculus

Project description:Transcription factors drive Tet2-mediated enhancer demethylation to reprogram cell fate [Bisulfite-Seq]

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Regulation of T cell cytokine expression by Tet2-mediated DNA demethylation [gene expression]

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

Regulation of host antiviral factors expression by TET2-mediated DNA demethylation

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

Transcription factors drive Tet2-mediated enhancer demethylation to reprogram cell fate [Bisulfite-Seq]

Project description:Studies of DNA hydroxy-methylation and chromatin state dynamics during highly-efficient somatic cell reprogramming

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TET2 coactivates gene expression through demethylation of enhancers

Project description:The tet methylcytosine dioxygenase 2 (TET2) enzyme catalyzes the conversion of the modified DNA base 5-methylcytosine to 5-hydroxymethylcytosine. TET2 is frequently mutated or dysregulated in multiple human cancers, and loss of TET2 is associated with changes in DNA methylation patterns. Here, using newly developed TET2-specific antibodies and the estrogen response as a model system for studying the regulation of gene expression, we demonstrate that endogenous TET2 occupies active enhancers and facilitates the proper recruitment of ERalpha. Knockout of TET2 by CRISPR-CAS9 leads to a global increase of DNA-methylation at enhancers resulting in attenuation of the estrogen response. We further identified a positive feedback loop between TET2 and ERalpha, which further requires MLL3/COMPASS at these enhancers. Together, this study reveals an epigenetic axis coordinating a transcriptional program through enhancer activation via DNA demethylation.

2018-10-04 | GSE120756 | GEO

Tet2-mediated DNA demethylation controls T cell cytokine expression [seq]

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

TET2 coactivates gene expression through demethylation of enhancers

Project description:TET2 coactivates gene expression through demethylation of enhancers

| PRJNA494397 | ENA

Tet2-mediated DNA demethylation controls T cell cytokine expression [array]

2015-04-12 | GSE48657 | GEO