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Series GSE119312 Query DataSets for GSE119312
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
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
Overall design Profile of histone H3K27me3 in WT and Utx KO CD8 T cells
Contributor(s) Yamada T
Citation(s) 30626691
Submission date Aug 31, 2018
Last update date Dec 01, 2021
Contact name Junpei Suzuki
Organization name Ehime University
Department Graduate School of Medicine
Lab Immunology
Street address Shitukawa
City Toon
ZIP/Postal code 791-0295
Country Japan
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (2)
GSM3369719 WT_H3K27me3
GSM3369720 Utx_KO_H3K27me3
BioProject PRJNA488724
SRA SRP159241

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Supplementary file Size Download File type/resource
GSE119312_RAW.tar 742.5 Mb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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