E-GEOD-48358 - Epigenetic modifications induced by Blimp-1 regulate CD8+ T cell memory progression during acute virus infection

Status
Released on 10 October 2013, last updated on 25 November 2013
Organism
Mus musculus
Samples (3)
Protocols (2)
Description
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. 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.
Experiment type
ChIP-seq 
Contacts
Hyun Mu Shin <hyunmu.shin@umassmed.edu>, H M Shin, L J Berg, R M Welsh, S M Kaech, T Guan, V N Kapoor
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
Files
Investigation descriptionE-GEOD-48358.idf.txt
Sample and data relationshipE-GEOD-48358.sdrf.txt
Processed data (2)E-GEOD-48358.processed.1.zip, E-GEOD-48358.processed.2.zip
Additional data (1)E-GEOD-48358.additional.1.zip
Links