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TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE206450 | GEO | 2022/07/15

REPOSITORIES: GEO

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TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner.

Project description:TET proteins mediate DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and other oxidative derivatives. We have previously demonstrated a dynamic enrichment of 5hmC during T and invariant natural killer T cell lineage specification. Here, we investigate shared signatures in gene expression of Tet2/3 DKO CD4 single positive (SP) and iNKT cells in the thymus. We discover that TET proteins exert a fundamental role in regulating the expression of the lineage specifying factor Th-POK, which is encoded by Zbtb7b. We demonstrate that TET proteins mediate DNA demethylation - surrounding a proximal enhancer, critical for the intensity of Th-POK expression. In addition, TET proteins drive the DNA demethylation of site A at the Zbtb7b locus to facilitate GATA3 binding. GATA3 induces Th-POK expression in CD4 SP cells. Finally, by introducing a novel mouse model that lacks TET3 and expresses full length, catalytically inactive TET2, we establish a causal link between TET2 catalytic activity and lineage specification of both conventional and unconventional T cells.

| S-EPMC9389146 | biostudies-literature

TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner [RNA-Seq]

2022-07-15 | GSE190230 | GEO

TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner [CUT&RUN]

2022-07-15 | GSE190228 | GEO

TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner [CATCH-SEQ]

2022-07-15 | GSE190227 | GEO

TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells.

Project description:TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4+CD8+ double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Transfer of purified Tet2-Tet3 DKO iNKT cells into immunocompetent recipient mice resulted in an uncontrolled expansion that was dependent on the nonclassical major histocompatibility complex (MHC) protein CD1d, which presents lipid antigens to iNKT cells. Our data indicate that TET proteins regulate iNKT cell fate by ensuring their proper development and maturation and by suppressing aberrant proliferation mediated by the T cell antigen receptor (TCR).

| S-EPMC5376256 | biostudies-literature

TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner.

Project description:TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner.

| PRJNA850953 | ENA

TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner [CUT&RUN]

Project description:TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner [CUT&RUN]

| PRJNA786482 | ENA

TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner [RNA-Seq]

Project description:TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner [RNA-Seq]

| PRJNA786480 | ENA

TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner [CATCH-SEQ]

Project description:TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner [CATCH-SEQ]