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The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells [WGBS]

ABSTRACT: The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells [WGBS]

PROVIDER: PRJNA592357 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10555600_1.fastq.gz	Fastqsanger.gz
	SRR10555600_2.fastq.gz	Fastqsanger.gz
	SRR10555601_1.fastq.gz	Fastqsanger.gz
	SRR10555601_2.fastq.gz	Fastqsanger.gz
	SRR10555602_1.fastq.gz	Fastqsanger.gz

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The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells [WGBS]

Project description:TET enzymes are essential for the stability and function of regulatory T cells (Tregs), which maintain immune homeostasis and self-tolerance and express the lineage-determining transcription factor Foxp3. We previously showed that Vitamin C acts through TET enzymes to maintain the demethylated status of CNS2, a key intronic enhancer of the Foxp3 gene that is essential for the stability of Foxp3 expression both in vivo and in vitro. Here we show that Vitamin C enables genome-wide features of “induced” T regulatory cells (iTregs) in vitro that overlap with those induced by TET proteins during Treg differentiation in vivo. Vitamin C enhances IL-2 responsiveness in iTregs by increasing phospho-STAT5 levels, STAT5 occupancy and DNA demethylation at key Treg-specific enhancers, and maintains the stable expression of Treg-specific genes including Foxp3 and Il2ra. Our data will be relevant to future studies of the association between plasma Vitamin C levels, Treg function and autoimmunity in humans.

2021-07-21 | GSE141151 | GEO

The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells [CMS-IP]

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The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells [ATAC-seq]

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The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells [RNA-seq]

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The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells

Project description:The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells

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The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells [ATAC-seq]

Project description:The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells [ATAC-seq]

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The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells [CMS-IP]

Project description:The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells [CMS-IP]

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The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells [RNA-seq]

Project description:The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells [RNA-seq]

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Project description:The Ten-eleven translocation (TET) family of dioxygenases can mediate cytosine demethylation by catalyzing the oxidation of 5-methylcytosine (5mC). TET-mediated DNA demethylation controls the proper differentiation of embryonic stem cells and TET proteins display functional redundancy during early gastrulation. However, it is unclear if TET proteins have functional significance in mammalian skeletal development. Here, we report that Tet deficiency in mesoderm mesenchymal stem cells results in severe defects of bone development. The existence of any single Tet gene allele can support early bone formation, suggesting a potential functional redundancy of TET proteins. Integrative analyses of RNA-seq, Whole Genome Bisulfite Sequencing (WGBS) and Assay for Transposase-Accessible Chromatin (ATAC-seq) demonstrate that TET-mediated demethylation increases the chromatin accessibility of target genes by RUNX2 and facilities RUNX2-regulated transcription. In addition, TET proteins interact with RUNX2 through their catalytic domain to regulate cytosine methylation around RUNX2 binding region. The catalytic domain is indispensable for TET proteins to regulate RUNX2 transcription activity on its target genes and to regulate bone development. These results demonstrate that TET proteins function redundantly to regulate RUNX2 activity via dual mechanisms and maintain skeletal homeostasis.

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Itaconate is an inhibitor of TET DNA dioxygenases

Project description:Itaconate is an inhibitor of TET DNA dioxygenases

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