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| Status |
Public on Feb 09, 2021 |
| Title |
UTX constrains antiviral CD8+ T cell responses during chronic virus infection |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Persistent virus infections can cause pathogenesis that is debilitating or lethal. During these infections, virus-specific T cells fail to protect due to weakened antiviral activity or failure to persist. These outcomes are governed epigenetically, though it is unknown which enzymes contribute to T cell loss or impaired function over time. Here, we show that T cell receptor-stimulated CD8+ T cells increase their expression of UTX (Ubiquitously transcribed Tetratricopeptide repeat, X-chromosome), an enzyme involved in demethylating histone-3 lysine-27 (H3K27), and reduce genome-wide H3K27-me3. UTX limits the frequency and durability of virus-specific CD8+ T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection in mice by promoting inhibitory receptor expression and apoptosis. UTX also increases effector gene expression to improve CTL-mediated protection, a process corresponding to reduced H3K27me3 at effector gene bodies. Thus, UTX guides gene expression patterns in CD8+ T cells, promoting antiviral activity while reducing CD8+ T cell durability.
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| Overall design |
RNA-seq, H3K27me3 CUT&RUN, and UTX CUT&Tag comparision of mouse WT P14 CD8+ T cells to Utx-/- P14 CD8+ T cells following adoptive transfer and LCMV-A22 infection. For RNA-seq, there were 3 WT replicates and 4 Utx -/- replicates 21 days post LCMV-A22 infection. For H3K27me3 CUT&RUN, there were 4 replicates for each group 15 days post LCMV-A22 infection. For UTX CUT&Tag, there were 4 WT replicates and 2 Utx -/- replicates 15 days post LCMV-A22 infection as well as 2 WT replicates prior to infection (day 0).
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| Contributor(s) |
Mitchell J, Lund M, Shpargel K, Starmer J, Magnuson T, Whimire J |
| Citation(s) |
33852868 |
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| Submission date |
Jan 15, 2020 |
| Last update date |
May 11, 2021 |
| Contact name |
Joshua Starmer |
| Organization name |
University of North Carolina at Chapel Hill
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| Department |
Genetics
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| Lab |
Magnuson
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| Street address |
120 Mason Farm Road
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| City |
Chapel Hill |
| State/province |
NORTH CAROLINA |
| ZIP/Postal code |
27599-7264 |
| Country |
USA |
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| Platforms (3) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (23)
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| Relations |
| BioProject |
PRJNA601463 |
| SRA |
SRP242086 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE143736_P14_D0_D15_UTX_WT_merge_peak.unique.final.counts.txt.gz |
272.9 Kb |
(ftp)(http) |
TXT |
| GSE143736_P14_D0_UTX_WT_merge.unique.bw |
23.3 Mb |
(ftp)(http) |
BW |
| GSE143736_P14_D15_K27me3_KO_merge.bw |
210.3 Mb |
(ftp)(http) |
BW |
| GSE143736_P14_D15_K27me3_KO_merge_hidden_mapq_10_analysis.bed.gz |
445.4 Kb |
(ftp)(http) |
BED |
| GSE143736_P14_D15_K27me3_KO_merge_hidden_mapq_10_vis.bed.gz |
4.4 Mb |
(ftp)(http) |
BED |
| GSE143736_P14_D15_K27me3_KO_merge_macs2_broadPeaks.bed.gz |
636.7 Kb |
(ftp)(http) |
BED |
| GSE143736_P14_D15_K27me3_WT_merge.bw |
778.9 Mb |
(ftp)(http) |
BW |
| GSE143736_P14_D15_K27me3_WT_merge_hidden_mapq_10_analysis.bed.gz |
192.5 Kb |
(ftp)(http) |
BED |
| GSE143736_P14_D15_K27me3_WT_merge_hidden_mapq_10_vis.bed.gz |
9.9 Mb |
(ftp)(http) |
BED |
| GSE143736_P14_D15_K27me3_WT_merge_macs2_broadPeaks.bed.gz |
648.3 Kb |
(ftp)(http) |
BED |
| GSE143736_P14_D15_UTX_KO_merge.unique.bw |
14.4 Mb |
(ftp)(http) |
BW |
| GSE143736_P14_D15_UTX_WT_merge.unique.bw |
34.8 Mb |
(ftp)(http) |
BW |
| GSE143736_RAW.tar |
670.0 Kb |
(http)(custom) |
TAR (of TXT) |
| GSE143736_edgeR_ecoli_scaling_factors.txt.gz |
389 b |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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