Project description:TMD8 cells were treated with either shIRF4 or control shRNA. Cells were lysed and the DNA was subjected to ATAC-sequencing to assess the changes in chromatin occupation.
Project description:Multiple Myeloma (MM) arises through oncogenic transformation of immunoglobulin-secreting
plasma cells. MM often co-opts the endoplasmic-reticulum (ER) stress mitigator, inositol
requiring enzyme 1 (IRE1), to sustain malignant growth. While certain MMs require enzymatic
IRE1-dependent activation of the ER-homeostatic transcription factor XBP1s, others display
nonenzymatic dependency on IRE1 that is not yet mechanistically understood. Interferon
regulatory factor 4 (IRF4) stimulates gene programs that promote immune-cell proliferation and cell cycle control by IRE1 in MM. Here we show that IRF4 acts as a key conduit of nonenzymatic cell cycle control by IRE1 in MM. IRE1 silencing increased inhibitory phosphorylation of IRF4, disrupting its chromatin-binding activity and mRNA transcription. IRF4 knockdown recapitulated, whereas IRF4 repletion reversed the anti-proliferative phenotype of IRE1 silencing. Functional studies revealed that IRF4 engages the E2F1 and CDC25A genes and promotes CDK2 activation to drive cell cycle progression. Our results advance mechanistic understanding of IRE1 and IRF4 in MM.
Project description:A gene expression study was conducted to understand the role of IRF4 in ABC like lymphomas. For this, IRF4 was silenced in TMD8 cell line alongside a control vector. Treated and control cell lines were subjected to gene expression measurement. Pathway analysis of differentially expressed gens showed antigen presentation pathways to be differentially regulated.
Project description:To investigate the genomic occupation of the transcription factor BmGATA, and the impact of BmNPV infection on its genomic occupation
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.
Project description:To explore whether IRF4 deficiency determine the epigenetic changes of mature NK cells is at the NKP cell stage, ATAC-seq was performed to analyze chromatin accessibility of NK cells from spleen WT, Irf4-/-, Irf4flox/flox and Ncr1cre+/-Irf4flox/flox mice.
Project description:The aim of experiment was to study on genome-wide level IRF4 target genes in chicken DT40 B cell line, by comparizon of gene expression profiles of IRF4-deficient DT40 cells with WT IRF4 DT40 cells .
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