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| Status |
Public on Jul 15, 2022 |
| Title |
TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner [CATCH-SEQ] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
Other
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| Summary |
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.
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| Overall design |
We compared the methylation status across the Zbtb7b locus, that encodes for Th-POK, in CD4 SP cells isolated from 4 control (wt), 3 Tet2-/-Tet3flx/flxCD4 cre (DKO) mice and 1 Tet2CDTet3flx/flxCD4 cre (TET2CDTET3KO) mouse by using CATCHseq
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| Contributor(s) |
Tsagaratou A, Äijö T |
| Citation(s) |
35990681 |
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| Submission date |
Dec 06, 2021 |
| Last update date |
Aug 22, 2022 |
| Contact name |
Tarmo Äijö |
| Organization name |
Flatiron Institute
|
| Department |
Center for Computational Biology
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| Street address |
162 5th Avenue
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| City |
New York |
| ZIP/Postal code |
10010 |
| Country |
USA |
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| Platforms (1) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE206450 |
TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner. |
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| Relations |
| BioProject |
PRJNA786483 |
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