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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 31, 2021 |
| Title |
Histone H3K27 demethylase negatively controls the memory formation of Ag-stimulated CD8+ T cells |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Although the methylation status of histone H3K27 plays a critical role in CD4+ T cell differentiation and its function, the role of Utx, histone H3K27 demethylase, in the CD8+ T cell-dependent immune response remains unclear. We therefore generated T cell-specific Utx knockout (Utx KO) mice to determine the role of Utx in CD8+ T cells. Wild-type (WT) and Utx KO mice were infected with Listeria monocytogenes expressing OVA to analyze the immune response of Ag-specific CD8+ T cells upon primary and secondary infections. There was no significant differences in the primary expansion of Ag-specific CD8+ T cells between WT and Utx KO mice. However, Utx deficiency resulted in an increased secondary expansion of Ag-specific CD8+ T cells. Adoptive transferred Utx KO CD8+ T cells resulted in increased numbers of CD127hi KLRG1lo memory precursors in the primary expansion and larger numbers of memory cells. We observed a decreased gene expression of effector-associated transcription factors, including Prdm1 encoding Blimp1, in Utx KO CD8+ T cells upon primary infection. We confirmed that the tri-methylation level of histone H3K27 in the Prdm1 gene loci in the Utx KO cells was higher than in the WT cells. The treatment of CD8+ T cells with Utx-cofactor α-ketoglutarate hampered the memory formation, while Utx-inhibitor GSK-J4 enhanced the memory formation and increased the secondary expansion in WT CD8+ T cells. These data suggest that Utx negatively controls the memory formation of Ag-stimulated CD8+ T cells by epigenetically regulating the expression of genes, including Prdm1. Based on these findings, we identified a critical link between Utx and the differentiation of Ag-stimulated CD8+ T cells upon infection
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| Overall design |
Profile of histone H3K27me3 in WT and Utx KO CD8 T cells
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| Contributor(s) |
Yamada T |
| Citation(s) |
30626691 |
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| Submission date |
Aug 31, 2018 |
| Last update date |
Dec 01, 2021 |
| Contact name |
Junpei Suzuki |
| Organization name |
Ehime University
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| Department |
Graduate School of Medicine
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| Lab |
Immunology
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| Street address |
Shitukawa
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| City |
Toon |
| ZIP/Postal code |
791-0295 |
| Country |
Japan |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA488724 |
| SRA |
SRP159241 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE119312_RAW.tar |
742.5 Mb |
(http)(custom) |
TAR (of WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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