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| Status |
Public on Sep 01, 2015 |
| Title |
T cell UTX promotes Tfh-mediated clearance of persistent virus infection |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
Epigenetic changes, including histone methylation, control T cell differentiation and memory formation, though the enzymes that mediate these processes are not clear. We show that UTX, a histone H3 lysine 27 (H3K27) demethylase, promotes the generation of T follicular helper (Tfh) cells, a CD4+ T cell subset essential for B cell antibody generation and clearance of chronic viral infections. Mice with T cell specific UTX deletion (UTX TKO mice) had fewer Tfh cells, showed defective germinal center formation, lacked virus-specific IgG production, and were unable to resolve chronic lymphocytic choriomeningitis virus infection. In UTX TKO T cells, decreased expression of IL-6R±, and other Tfh-related loci, was associated with increased H3K27 methylation. Additionally, Turner Syndrome subjects, who are predisposed to chronic ear infections, have reduced UTX expression in immune cells and decreased Tfh frequency. Thus, we identify a critical link between UTX in T cells and immunity to infection.
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| Overall design |
Mice were infected with chronic LCMV and sorted for Tfh on day 21 pi (sorted for: CD4+CXCR5+CD62Llo T cell). ChIP-Seq and RNA-Seq on WT and Utx KO cells.
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| Contributor(s) |
Cook KD, Shpargel KB, Whitfield-Larry F, Starmer J, Conley B, Allard DE, Rager JE, Fry RC, Davenport ML, Magnuson T, Whitmire JK, Su MA |
| Citation(s) |
26431949 |
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| Submission date |
Jan 14, 2015 |
| Last update date |
May 15, 2019 |
| 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 (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (13)
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| Relations |
| BioProject |
PRJNA272610 |
| SRA |
SRP052232 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE64969_RAW.tar |
153.2 Mb |
(http)(custom) |
TAR (of BEDGRAPH, TXT) |
| GSE64969_README.txt |
394 b |
(ftp)(http) |
TXT |
| GSE64969_ko_norm_rmdup.bedgraph.gz |
50.7 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE64969_wt_norm_rmdup.bedgraph.gz |
17.0 Mb |
(ftp)(http) |
BEDGRAPH |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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