Project description:As a part of a modelling experiment for transcriptional control of mouse primordial germ cell specification, the transcription factor BLIMP1 was transiently expressed in the mouse p19 embryonal carcinoma cell line and its genome wide binding sites were defined using ChIPseq.
Project description:To identify the role of BLIMP1 in Waldenström's macroglobulinemia, the PRDM1 transcript was targeted using an artificial miRNA. RNAseq was used to compare it to a non-targeting control in the RPCI-WM1 cell line. To determine the role of EZH2 in Waldenström's macroglobulinemia, the RPCI-WM1 cell line was treated with 0.3µM of the EZH2 inhibitor Tazemetostat, compared to DMSO vehicle control by RNAseq. ChIPseq was performed for the factors BLIMP1 and H3K27me3 in the RPCI-WM1, OPM-2 and NCI-H929 cell lines, along with ChIPseq for EZH2 in the NCI-H929 cell line.
Project description:To clarify the potential BLIMP1 downstream target regulating PD-L1 expression, we performed proteomics analysis using BLIMP1 Hep3B cells and control cells. Proteomics analysis revealed that SPI1 may serve as a pivotal transcriptional factor that enhances PD-L1 expression by acting as a downstream effector of BLIMP1.
Project description:Regulatory T (Treg) cells are required for peripheral tolerance. Recent evidence indicates that Treg cells can adopt specialized differentiation programs in the periphery that are controlled by transcription factors usually associated with T helper differentiation. We demonstrate that expression of the transcription factor Blimp1 defines a population of Treg cells that localize predominantly to mucosal sites and produces IL-10. Blimp1 is required for IL-10 production by these cells and for their tissue homeostasis. A list of differentially expressed genes were identified from this whole-genome expression profiling experiment. Mouse Blimp1 +/gfp and Blimp1 gfp/gfp regulatory T cells were analyzed. Three replicates each.
Project description:Antibody-secreting plasma cells are the terminal stage of the B-cell lineage. Plasma cell differentiation requires a major resetting of gene expression to silence the B cell transcriptional program, whilst establishing secretory function and long-term survival. The transcription factors Blimp1 and Irf4 are essential for the initial differentiation of activated B cells to antibody-secreting cells, however their function in mature plasma cells remains elusive. We have found that while Irf4 was essential for plasma cell survival, Blimp1 was dispensable. Blimp1-deficient cells retained the unique plasma cell transcriptional signature, but lost the ability to secrete antibody or to maintain the characteristic size and ultrastructure of plasma cells. Blimp1 was required for full expression of many components of the unfolded protein response (UPR), including Xbp1 and Atf6, as well as for the appropriate processing of Igh mRNA. The overlap of Blimp1 and Xbp1 function was restricted to the UPR genes, with Blimp1 uniquely regulating activity of the mTOR pathway, plasma cell size and morphology. These studies establish Blimp1 as a major regulator of the UPR pathway that is also required for the unique metabolic requirements of plasma cells enabling the secretion of protective antibody. RNA-seq was performed on wild type, Blimp1-/- and Xbp1-/- mouse plasma cells. Between two to four biological replicates were generated and sequenced for each sample.
Project description:Blimp1 is an essential regulator of plasma cells. Here we studied its functions in early plasmablast differentiation by identifying regulated Blimp1 target genes. Blimp1 promoted plasmablast migration and adhesion by controlling many genes involved in these processes. It repressed several transcription factor genes and Aicda, thus silencing B-cell-specific gene expression, antigen presentation and class switch recombination in plasmablasts. It also directly activated genes, leading to increased expression of the plasma cell regulator IRF4 and proteins involved in immunoglobulin secretion. Blimp1 strongly induced immunoglobulin gene transcription by controlling the activity of Igh and Igk 3’ enhancers and regulated the posttranscriptional switch of expression from the membrane-bound to secreted immunoglobulin heavy-chain by activating Ell2. Notably, Blimp1 recruited chromatin-remodeling and histone-modifying complexes to regulate its target gene. Hence, many essential functions of plasma cells are under Blimp1 control.
Project description:Antibody-secreting plasma cells are the terminal stage of the B-cell lineage. Plasma cell differentiation requires a major resetting of gene expression to silence the B cell transcriptional program, whilst establishing secretory function and long-term survival. The transcription factors Blimp1 and Irf4 are essential for the initial differentiation of activated B cells to antibody-secreting cells, however their function in mature plasma cells remains elusive. We have found that while Irf4 was essential for plasma cell survival, Blimp1 was dispensable. Blimp1-deficient cells retained the unique plasma cell transcriptional signature, but lost the ability to secrete antibody or to maintain the characteristic size and ultrastructure of plasma cells. Blimp1 was required for full expression of many components of the unfolded protein response (UPR), including Xbp1 and Atf6, as well as for the appropriate processing of Igh mRNA. The overlap of Blimp1 and Xbp1 function was restricted to the UPR genes, with Blimp1 uniquely regulating activity of the mTOR pathway, plasma cell size and morphology. These studies establish Blimp1 as a major regulator of the UPR pathway that is also required for the unique metabolic requirements of plasma cells enabling the secretion of protective antibody.
Project description:Comparative analysis of regulation of gene expression by Blimp1 in regulatory and effector CD4+ T cells. The hypothesis tested in the present study was that Blimp1 differentially regualte gene expression in different T cell subsets. Results provide important information of mechanisms underlying regulation of gene expression by Blimp1 in T cells