Transient expression of Bcl6 is sufficient for oncogenic function and induction of mature B-cell lymphoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE56310 | GEO | 2014/03/28
SECONDARY ACCESSION(S): PRJNA242887
REPOSITORIES: GEO
Similar Datasets
Project description:Reduced representation bisulfite sequencing (RRBS) of hematopoeitic stem/progenitor cells and mature B-cells from wild-type mice and mice transiently expressing Bcl6 under control of the Sca1 promoter. CBAxC57BL/6J mice were engineered to transiently express a Bcl6 cDNA in hematopoeitic stem/progenitor cells under control of the Sca1 promoter and then delete the transgene by cre-mediated recombination upon expression of Cd79a (Sca1-BCL6?). Hematopoeitic stem/progentior cells (HSPC, Sca1+Lin-) from the bone marrow and mature B-cells (B220+) from the peripheral blood were isolated from these mice and wild-type CBAxC57BL/6J mice by fluorescence activated cell sorting. Cells from 6-9 mice were pooled, for a total of 4 experimental conditions. DNA was extracted for each condition and analyzed by reduced representation bisulfite sequencing.
2014-03-28 | E-GEOD-56310 | biostudies-arrayexpress
Project description:Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma and can be separated into two subtypes based upon molecular features with similarities to germinal centre B-cells (GCB-like) or activated B-cells (ABC-like). Here we identify gain of 3q27.2 as being significantly associated with adverse outcome in DLBCL and linked with the ABC-like subtype. This lesion includes the BCL6 oncogene, but does not alter BCL6 transcript levels or target-gene repression. Separately, we identify expression of BCL6 in a subset of human haematopoietic stem/progenitor cells (HSPCs). We therefore hypothesize that BCL6 may act by 'hit-and-run' oncogenesis. We model this hit-and-run mechanism by transiently expressing Bcl6 within murine HSPCs, and find that it causes mature B-cell lymphomas that lack Bcl6 expression and target-gene repression, are transcriptionally similar to post-GCB cells, and show epigenetic changes that are conserved from HSPCs to mature B-cells. Together, these results suggest that BCL6 may function in a 'hit-and-run' role in lymphomagenesis.
| S-EPMC4321731 | biostudies-literature
Project description:We analyzed the transcriptome differences of BCL6-sufficient (CD4-Cre) and -insufficient (CD4-CrexBcl6fl/+) OT-II TFH cells. CD4-CrexBcl6fl/+ or control CD4-Cre OT-II T cells were transferred into CD45.1 Sap-/- mice. At day 3 post NP-OVA immunization, CXCR5hiPD-1hi TFH cells were sort-purified from the draining lymph node and prepared for RNA-seq analysis. Two technical repeats of ~200 cells per sample from each of 3 mice were included. BCL6-insufficient TFH cells differentially expressed many genes; among those downregulated were Stim1 and Plcg1, which code for STIM1 and PLCg1, respectively, that both impinge on calcium signaling downstream of TCR activation. Moreover, KEGG pathway analyses revealed that the calcium signaling-related pathway was generally upregulated in wildtype as compared to BCL6-insufficient TFH cells. These data support the notion that BCL6 control follicular T-B interactions by regulating multiple target genes involved in antigen-triggered calcium signaling in T cells.
2021-07-30 | GSE180924 | GEO
Project description:Most small-molecule protein degraders act as interface stabilizers ‘molecular glues’ between E3 ubiquitin ligases and target proteins to induce ternary complex formation and ubiquitin-dependent target protein degradation. Here we report polymerization as a novel mechanism for small molecule-induced degradation. Using functional screens in combination with molecular and biochemical assays, we found that BI-3802, which binds to the BTB domain of the oncogenic transcription factor BCL6, induces polymerization of BCL6 into regular helical structures in vitro and foci in vivo. Polymerization precedes degradation by the SIAH1 E3 ubiquitin ligase. Hereby, a VxP amino acid motif on BCL6, distal from the drug-binding BTB domain, is required for SIAH1 binding, ubiquitination and BI-3802-induced degradation. Our findings propose that small molecule-induced polymerization is not only a new modality for targeted protein degradation, but also provides synthetic biology with a tool for tunable protein polymerization and opens new avenues for future drug design.
2020-11-20 | PXD016185 | Pride
Project description:Gene expression data from CD22+B220+ FACS-purified splenocytes of adult wild-type, Sca1-Bcl6(floxed) and Sca1-Bcl6(Δ) knock-in CBAxC57BL/6J mice. The Bcl6 floxed vector was generated by inserting the mouse Bcl6–IRES-eGFP cassette flanked by loxP sites into the ClaI site of the pLy6 vector. The transgene fragment was excised from its vector by restriction digestion with NotI, purified and injected into CBAxC57BL/6J fertilized eggs. Two independent transgenic lines were generated and analyzed. Sca1-Bcl6(floxed) mice were bred to mb1-Cre mice to generate Sca1-Bcl6(Δ) mice. Splenic B220+CD22+ cells were FACS purified from wild-type, Sca1-Bcl6(floxed) and Sca1-Bcl6(Δ) mice and arrayed using Affymetrix Mouse Gene 1.0 ST arrays.
2014-03-01 | E-GEOD-36503 | biostudies-arrayexpress
Project description:Gene expression data from CD22+B220+ FACS-purified splenocytes of adult wild-type, Sca1-Bcl6(floxed) and Sca1-Bcl6(Δ) knock-in CBAxC57BL/6J mice.
2014-03-01 | GSE36503 | GEO
Project description:Innate T cells, including invariant natural killer T (iNKT) and mucosal-associated innate T (MAIT) cells, are a heterogeneous T lymphocyte population with effector properties pre-programmed during their thymic differentiation. How this program is initiated is currently unclear. Here, we show that the transcription factor BCL6 is transiently expressed in iNKT cells upon exit from positive selection and is required for their proper development beyond stage 0. Notably, development of MAIT cells is also impaired in Bcl6-deficient mice. We found that BCL6 regulates the expression of genes that are associated with the innate T cell lineage, including PLZF and its targets. BCL6 contributes to a chromatin accessibility landscape that is permissive for the expression of development-related genes and inhibitory for genes associated with naïve T cell programs. Our results reveal novel functions for BCL6 and indicate that this transcription factor controls the inception of innate T cell lineage programming.
2021-07-03 | GSE134211 | GEO
Project description:Innate T cells, including invariant natural killer T (iNKT) and mucosal-associated innate T (MAIT) cells, are a heterogeneous T lymphocyte population with effector properties pre-programmed during their thymic differentiation. How this program is initiated is currently unclear. Here, we show that the transcription factor BCL6 is transiently expressed in iNKT cells upon exit from positive selection and is required for their proper development beyond stage 0. Notably, development of MAIT cells is also impaired in Bcl6-deficient mice. We found that BCL6 regulates the expression of genes that are associated with the innate T cell lineage, including PLZF and its targets. BCL6 contributes to a chromatin accessibility landscape that is permissive for the expression of development-related genes and inhibitory for genes associated with naïve T cell programs. Our results reveal novel functions for BCL6 and indicate that this transcription factor controls the inception of innate T cell lineage programming.
2020-07-27 | GSE134210 | GEO
Project description:We aimed to identify the response mechanism to EGFR tyrosine kinase inhibition. A431 cells were transfected with mock siRNA or BCL6 siRNA. Cells were then treated with gefitinib. Harvesting was done at 0h, at 24h and at 48h. Two TMT10plex sets were organized as follows: TMT set1: mock 0h (3x, channels 126, 127N and 127C), mock 24h (3x, 128N, 128C and 129N), mock 48h (3x, 129C, 130N, 130C) and internal pooled standard (131) composed from equal aliquots of all samples (mock siRNA and BCL6 siRNA). TMT set2: siBCL6 0h (3x, channels 126, 127N and 127C), siBCL6 24h (3x, 128N, 128C and 129N), siBCL6 48h (3x, 129C, 130N, 130C) and the same internal pooled standard (131) as for set 1.
2020-12-09 | PXD016605 | Pride
Project description:gene expression data from wild-type and Bcl6-/- regulatory T cells in order to find genes regulated by Bcl6 in Treg cells FoxP3+ Tregs were sorted from wild-type (WT) and Bcl6-/- (KO) mice-- 8 samples, 2 from each type of Treg, 2 WT and 2 KO
2012-12-05 | E-GEOD-40493 | biostudies-arrayexpress