Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE48358 | GEO | 2013/10/10

SECONDARY ACCESSION(S): PRJNA209842

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

Project 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. NaM-CM-/ve 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.

2013-10-10 | E-GEOD-48358 | biostudies-arrayexpress

Gene expression in LCMV-specific Blimp-1 deficient effector CD8+ T cells compared to wildtype effector CD8+ T cells

Project description:Antigen-specific effector CD8+ T cells deficient in Blimp-1 (Prdm1) do not acquire maximal effector functions, evade terminal differentiation, and more rapidly acquire some hallmark properties of memory CD8+ T cells. In this study, we compared the gene expression profiles of wildtype and Prdm1-/- LCMV-specific effector CD8+ T cells to better understand the molecular mechanisms underlying this striking phenotype. DNA microarray analysis was performed of DbGP33-41 and DbNP396-404 tetramer-positive effector CD8+ T cells FACS-sorted at day 8 post-LCMV infection from four independent samples of either Blimp-1 conditional knockout mice (CKO; Blimp-1flox/flox x GranzymeB-cre+) or wildtype (WT) littermate controls.

2010-08-19 | E-GEOD-17211 | biostudies-arrayexpress

Gene expression in LCMV-specific Blimp-1 deficient effector CD8+ T cells compared to wildtype effector CD8+ T cells

2009-07-22 | GSE17211 | GEO

BLIMP-1 is insufficient to induce antibody secretion in the absence of IRF4

Project description:Differentiation of B cells into antibody secreting cells (ASCs), plasmablasts and plasma cells, is regulated by a network of transcription factors. Within this network factors including PAX5 and BCL6 prevent ASC differentiation and maintain the B cell phenotype whereas BLIMP-1 and high IRF4 expression promote plasmacytic differentiation. BLIMP-1 is thought to induce immunoglobulin secretion. While IRF4 is needed for the survival of ASCs, its role in the regulation of antibody secretion has been controversial. BCL6-deficient DT40 B cell line has upregulated BLIMP-1 expression and secrete antibodies. In order to study the role of IRF4 in regulation of antibody secretion we have created a double knockout (DKO) DT40 B cell line deficient in both IRF4 and BCL6. This DKO cell line did not upregulate PRDM1 (the gene encoding for BLIMP-1) expression or secrete IgM. Even enforced BLIMP-1 expression in DKO cells or IRF4-deficient cells could not induce IgM secretion while it did in WT cells. However, enforced IRF4 expression in DKO cells induced strong IgM secretion. Our findings support a model where IRF4 expression in addition to BLIMP-1 expression is required to induce antibody secretion.

2018-03-05 | GSE94836 | GEO

Blimp-1 moulds the epigenetic architecture of IL-21-mediated autoimmune diseases through an autoregulatory circuit

Project description:To unravel how Blimp-1 systematically manipulates the global transcriptional landscape in CD4 T cells to contribute to autoimmune progression, we performed RNA sequencing analysis in Blimp-1 transgenic (BTg) or Blimp1-deficient (CKO) NOD mice

2022-12-31 | GSE200545 | GEO

Comparison of the transcripts in control and Blimp-1-deficient keratinocytes

Project description:We performed microarray analysis to examine the differential gene expression profiles between Prdm1 (Blimp-1)-deleted and control keratinocytes. Keratinocytes isolated from Prdm1-floxed K5-CreER positive (CKO) mice were cultured in the presence of 4OHT to induce deletion of the Prdm1 allele in vitro. Prdm1-floxed K5-CreER positive (CKO) keratinocytes treated with the ethanol solvent control (EtOH) or Prdm1-floxed K5-CreER negative (control) keratinocytes treated with 4OHT or EtOH served as controls. Microarray analyses revealed that there were 93 genes up-regulated and 109 genes down-regulated by more than 2-fold in the CKO + 4OHT group in comparison with the CKO + EtOH, Ctrl + 4OHT or Ctrl + EtOH groups. Several corneocytes-related genes, including Rptn, Lce1f, Krt1 and Lce1d, are significantly down-regulated and several cytokines/chemokines, including Cxcl1, Cxcl2, Cxcl5 and Il24, are significantly up-regulated upon the deletion of Prdm1 in vitro. We analyzed the transcription profiles in control and Blimp-1-deficient keratinocytes using the GeneChipÂ® Mouse Expression Array 430A.

2013-04-02 | E-GEOD-34586 | biostudies-arrayexpress

miRNA expression in Blimp-1-deficient dendritic cells

Project description:Expression of Blimp-1 was specifically deleted in dendritic cells (DCs) by breeding Blimp-1 flox and CD11c-CRE mice. MiRNA expression was evaluated and compared from DCs, CD4+ T cells and total B cells from spleens of control and Blimp-1 KO mice. Age-matched (6-10 weeks old) female mice from control and Blimp-1 KO mice were sacrificed and spleens were collected. CD11chi/MHCIIhi DCs, CD4+TCRb+ T cells and B220+ B cells were sorted by FACSaria. MiRNA was measured from the total RNA preparation.

2013-09-05 | E-GEOD-40587 | biostudies-arrayexpress

Analysis of Blimp-1 and Irf-1 genomic binding in wild type and Prdm1/Blimp-1 mutant embryonic gut

Project description:The goal of this study was to profile Blimp1 binding in E18.5 small intestine using a Blimp-1-eGFP knock-in allele, and to compare Blimp-1-eGFP genomic binding with Irf-1 genomic binding in normal small intestine. Changes in Irf-1 binding between wild type and Prdm1/Blimp-1 mutant small intestine were also assessed. ChIP-seq was performed for Blimp-1-eGFP in duplicate in E18.5 small intestine expressing the fusion protein using anti-GFP antibody. As a negative control a single anti-GFP ChIP was also performed in wild type small intestine. ChIP-seq for Irf-1 was performed in duplicate in both wild type and Prdm1/Blimp-1 mutant E18.5 small intestine using an anti-Irf-1 antibody. Duplicate IgG ChIP control in wild types was performed as a negative control. All samples had an associated input chromatin sample sequenced.

2015-07-10 | E-GEOD-66069 | biostudies-arrayexpress

Transcriptome profiling of Blimp-1-deficient B cells from distinct divisions during plasma cell differentiation

Project description:To examine the cell division that Blimp-1 functioned during B cell differentiation we adoptively transferred CellTrace Violet labeled Blimp-1-deficient or control B cells into congenically disparate uMT hosts. Following transfer, mice were innoculated with LPS to induce B cell differentiation and 72 hours later cells from distinct divisions were FACS sorted for RNA-seq

2020-07-07 | GSE136275 | GEO

miRNA expression in Blimp-1-deficient dendritic cells

2013-09-05 | GSE40587 | GEO