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Graded Expression of IRF4 Coordinates Isotype Switching with Plasma Cell Differentiation

ABSTRACT: Graded Expression of IRF4 Coordinates Isotype Switching with Plasma Cell Differentiation

OTHER RELATED OMICS DATASETS IN: GSE6337

PROVIDER: PRJNA99637 | ENA |

REPOSITORIES: ENA

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Graded Expression of IRF4 Coordinates Isotype Switching with Plasma Cell Differentiation

Project description:Determine irf4 target genes in mouse B cells undergoing LPS differentiation to plasma cells in vitro. Determine targets of IRF4 by overexpression in a human GCB cell line. Keywords: cell type comparison design

2006-11-24 | GSE6337 | GEO

Human B cell isotype switching origins of IgE

Project description:Human B cell isotype switching origins of IgE

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Graded responses to variable TCR signaling are encoded in the affinities of AICE-containing enhancers responding to BATF and IRF4 [gene expression]

Project description:Variable strengths of T cell receptor (TCR) signaling can produce divergent outcomes for T cell development and function. The mechanisms leading to different outcomes are incompletely understood, but may include distinct activation thresholds for different transcription factors as well as distinct sensitivities among target genes to transcription factors. IRF4 is one transcription factor implicated in responses to variable TCR signal strength. IRF4 expression increases uniformly with increasing TCR signal strength (i.e., analog), but it is unclear how IRF4 induced distinct genes at different levels, rather than different amounts of the same genes. Here, we analyzed global gene expression in TH2 cells and used ChIP-seq to define the relationship between TCR signal strength, enhancer occupancy and transcriptional activity for BATF/IRF4-dependent genes. We show that enhancers exhibit a spectrum of affinity for the BATF/IRF4 ternary complex mediate graded responsiveness of individual genes to increasing TCR signal strength. Differential gene induction by BATF and IRF4 occurs through interaction with enhancer elements of different affinity for BATF/IRF4 complexes. The increased resolution of factor binding site identified using ChIP-exo allowed the identification of a novel AICE2 motif binding BATF/IRF4 with higher affinity and that this may explain the protective role of a single nucleotide polymorphism in the CTLA-4 locus known to decrease the incidence of autoimmune diseases.

2017-03-27 | GSE85173 | GEO

Transcriptional profiling of IRF4 -/- vs IRF4 +/- T-cells under Th17 polarizing conditions

Project description:Transcriptional profiling of T-cells isolated from spleen of IRF4 -/- mice and cultured under Th17 polarizing conditions for 42 hrs compared to cells similarly isolated and cultured from spleen of IRF4 +/- mice. The aim of the study was to identify global misexpression of genes in IRF4 -/- cells and hence identify key pathways regulated by IRF4 during Th17 differentiation. Two-condition experiment, IRF4 -/- vs IRF4 +/- Th17 cells at 42hrs. Biological replicates: 3 for each condition

2012-09-13 | E-GEOD-40726 | biostudies-arrayexpress

Transcriptional profiling of IRF4 -/- vs IRF4 +/- T-cells under Th17 polarizing conditions

2012-09-13 | GSE40726 | GEO

Origin of immunoglobulin isotype switching.

Project description: Not available

| S-EPMC3360817 | biostudies-literature

A screen to indentify non-covalent isotype-specific SUMO binders

Project description:In this study we identify SUMO isotype-specific non covalent binders. The different isotypes include SUMO1, SUMO2 and a 3xSUMO2 chain.

2021-01-29 | PXD013842 | Pride

Expression data from murine irf4-/- and irf4+/+ mature B cells purified by magnetic cell separation

Project description:Gene expression profiling of murine irf4-/- and irf4+/+ splenic B cells identifies genes regulated by the transcription factor IRF4 in quiescent mature B cells.

2013-11-22 | GSE51932 | GEO

Myeloma IRF4 target genes - Agilent

Project description:The goal of this gene expression study was to identify genes whose expression depends on the transription factor IRF4 by knocking down it's expression using shRNA in two IRF4+ myeloma cell lines. Keywords: time series design Two myeloma lines were analyzed over a time course of IRF4-targeted shRNA induction. There are 3 time courses: two using KMS12 (biological replicates) and one with SKMM1. Within each time course there are technical replicates.

2010-05-26 | E-GEOD-9067 | biostudies-arrayexpress

Metabolic crosstalk between skeletal muscle cells and liver through IRF4-FSTL1 in 2 nonalcoholic steatohepatitis

Project description:In this study Guo et al. revealed an endocrine pathway regulated by skeletal muscle IRF4 that manipulates liver pathology. Mice with skeletal muscle specific ablation of IRF4 show ameliorated liver steatosis, inflammation, and fibrosis, without changes in body weight on nonalcoholic steatohepatitis (NASH) diet. Proteomics analysis of mouse serum suggested that follistatin-like protein 1 (FSTL1) might link the communication between muscle and liver. Dual luciferase assays showed that IRF4 could transcriptionally regulate FSTL1 and reconstitution of FSTL1 expression in muscle of F4MKO mice was sufficient to restore the liver pathology. Furthermore, co-culture experiments verified that FSTL1 exerts its function in hepatocyte, macrophage, and hepatic satellite cells through CD14 and DIP2A, CD14, DIP2A, respectively. In human, serum FSTL1 is increased in NASH patients, but the mRNA level of Fstl1 and its receptors are decreased in NASH liver biopsy, suggesting the increased serum FSTL1 is from skeletal muscle as studied in F4MKO mice. These data unveiled a signaling pathway from skeletal muscle to liver via IRF4-FSTL1-DIP2A/CD14 in the pathogenesis of NASH.

2023-09-13 | PXD045324 | Pride

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