Epigenetic Modifications Induced by Blimp-1 Regulate CD8+ T Cell Memory Progression during Acute Virus Infection.
Shin, Hyun Mu 1,4; Kapoor, Varun N. 1,4; Guan, Tianxia 2,3; Kaech, Susan M. 2,3; Welsh, Raymond M. 1; Berg, Leslie J. 1,*
[Article] Immunity. 39(4):661-675, October 2013.

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: The transcription factor Blimp-1 regulates the overall accumulation of virus-specific CD8 T cells during acute viral infections. We found that increased proliferation and survival of Blimp-1-deficient CD8 T cells resulted from sustained expression of CD25 and CD27 and persistent cytokine responsiveness. Silencing of Il2ra and Cd27 reduced the Blimp-1-deficient CD8 T cell response. Genome-wide chromatin immunoprecipitation (ChIP) sequencing analysis identified Il2ra and Cd27 as direct targets of Blimp-1. At the peak of the antiviral 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, Il2ra and Cd27 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 and enhances the numbers of short-lived effector cells while suppressing the development of memory-precursor CD8 T cells.

Highlights:

* Blimp-1 represses CD25 and CD27 expression in CD8 T cells

* The amount of CD25 and CD27 regulated by Blimp-1 dictates the fate of CD8 T cells

* ChIP-seq analysis identifies Blimp-1 target genes in CD8 T cells

* Blimp-1 recruits G9a and HDAC2 to induce repressive chromatin modifications

(C) 2013Elsevier, Inc.