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| Status |
Public on Oct 10, 2013 |
| Title |
Epigenetic modifications induced by Blimp-1 regulate CD8+ T cell memory progression during acute virus infection |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Blimp-1 regulates the overall accumulation of virus-specific CD8+ T cells during acute viral infections. Increased proliferation and survival of Blimp-1-deficient CD8+ T cells is promoted by persistent cytokine responsiveness, resulting from sustained expression of CD25 and CD27. Knockdown of these genes reduced the Blimp-1-deficient CD8+ T cell response. Genome-wide ChIP-sequencing analysis identified CD25 and CD27 genes as direct targets of Blimp-1. At the peak of the anti-viral response, but not earlier, Blimp-1 recruited the histone modifying enzymes G9a and HDAC2 to the Il2ra and Cd27 loci, thereby repressing expression of these genes. In the absence of Blimp-1, the Il2ra and Cd27 genes exhibited enhanced histone H3-acetylation and reduced histone H3K9-trimethylation. These data elucidate a central mechanism by which Blimp-1 acts as an epigenetic regulator, enhancing the numbers of short-lived effector cells while suppressing the development of memory precursor CD8+ T cells.
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| Overall design |
Naïve CD8+ T cells from OT-I TCR transgenic Rag1-/- mice were stimulated with anti-CD3 and anti-CD28 for three days in vitro, in the presence of IL-2 to up-regulate Blimp-1 protein. Genome-wide mapping of Blimp-1 binding in mouse CD8+ T cells was conducted.
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| Contributor(s) |
Shin HM, Kapoor VN, Guan T, Kaech SM, Welsh RM, Berg LJ |
| Citation(s) |
24120360 |
| Submission date |
Jun 27, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Hyun Mu Shin |
| E-mail(s) |
hyunmu.shin@snu.ac.kr
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| Organization name |
Seoul National University College of Medicine
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| Department |
Biomedical Sciences
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| Lab |
Laboratory of Immunobiology
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| Street address |
Biomedical Science Building 202, 103 Daehakro, Jongro-gu
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| City |
Seoul |
| ZIP/Postal code |
110-799 |
| Country |
South Korea |
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| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA209842 |
| SRA |
SRP026363 |
