Transcription factor Zbtb1 interacts with bridging factor Lmo2 and maintains the T-lineage differentiation capacity of lymphoid progenitor cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA821203 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18518543.fastq.gz | Fastqsanger.gz | |||
| SRR18518544.fastq.gz | Fastqsanger.gz | |||
| SRR18518545.fastq.gz | Fastqsanger.gz | |||
| SRR18518546.fastq.gz | Fastqsanger.gz | |||
| SRR18518547.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 21 |
Similar Datasets
Project description:Hematopoietic stem and progenitor cells are able to differentiate into all blood cell types. Regulatory mechanisms underlying pluripotency in progenitors, such as the ability of lymphoid progenitor cells to differentiate into T-lineage, are not fully understood. We have previously reported that Lmo2, a bridging factor in large transcriptional complexes, is essential to retain the ability of lymphoid progenitors to differentiate into T-lineage. However, biochemical characterization of Lmo2 protein complexes in physiological hematopoietic progenitors has remained obscure. In this study, we identified around 600 of Lmo2 interacting molecules in a lymphoid progenitor cell line by two-step affinity purification with LC-MS/MS analysis. Among them, we found that Zbtb1 and Cbfa2t3 are functionally important binding partners of Lmo2. CRISPR/Cas9-mediated acute disruption of Zbtb1 or Cbfa2t3 in a lymphoid progenitor line or BM-derived primary hematopoietic progenitors caused significant defects in the initiation of T cell development when Notch signal is activated. Transcriptome analysis of Zbtb1- or Cbfa2t3-deficient lymphoid progenitors reveled that Tcf7, one the earliest Notch-target genes, is a common target of both factors. ChIP-seq analysis clearly showed that Lmo2, Zbtb1 and Cbfa2t3 co-bind to the Tcf7 upstream enhancer region, where is occupied by Notch intracellular domain/RBPJ transcriptional complex after Notch stimulation, in lymphoid progenitors. Moreover, transduction of Tcf7 restored the defect in the T-lineage potential of Zbtb1-deficient lymphoid progenitor cells. Thus, in lymphoid progenitors, Lmo2/Zbtb1/Cbfa2t3 complex directly binds to the Tcf7 locus and maintains responsiveness to the Notch-mediated inductive signaling for the T-lineage program.
2022-09-10 | GSE199696 | GEO
Project description:Lmo2 is an oncogenic transcription factor that is a frequent target of chromosomal abnormalities in this T-cell acute lymphoblastic leukemia (T-ALL). In transgenic mouse models, overexpression of Lmo2 causes thymocyte self-renewal leading to T-cell leukemia with long latency. However, the requirement of Lmo2 for maintenance of overt leukemia is poorly understood. We found that Lyl1, a critical cofactor for Lmo2-induced leukemia, is frequently lost in cell lines derived from Lmo2-transgenic mice, raising the possibility that Lmo2 function is dispensable at this stage. To study this, we developed a Tetracycline-repressible knock-in mouse model (Vav-TRE-Lmo2), which expresses Lmo2 throughout the haematopoietic system. This led to specific effects on T-cell development and the development of T-cell leukemia with long latency, preceded by the presence of self-renewing T-cells in the thymus. Repression of Lmo2 overcame the Lmo2-induced thymocyte developmental block at the preleukemic stage and led to elimination of Lmo2-induced thymocyte self-renewal in vivo. In contrast, Lmo2 function was dispensable for the majority of overt Lmo2-induced T-cell leukemias as well as leukemia-derived cell lines, implying an evolution of oncogene addiction in the majority of T-cell leukemias. Lmo2-dependence in T-ALL was associated with an immature gene expression profile, but could not be predicted by immunophenotype or assessment of Notch pathway activation. Thus, Lmo2 can give rise to both Lmo2-depenent and –independent T-cell leukemias. The Vav-TRE-Lmo2 model should be useful to determine the molecular features associated with Lmo2-dependence, as well as the critical components of the Lmo2-induced self-renewal pathways in T-ALL.
2022-01-01 | GSE125674 | GEO
Project description:Beauveria basiana is a well-known filamentous entomopathogenic fungus. Oxidation tolerance is an important determinant to fungal pathogenicity and biocontrol potential. B. bassiana transcriptional co-activator multiprotein bridging factor 1 (BbMBF1) contributes to fungal resistance to the oxidative stress. The interactome of BbMBF1 was revealed by the qualitative proteomic analysis integrated with the immuno-precipitation. This study is sought to unveil the comprehensive protein interaction of BbMBF1 and isolate the BbMBF1-mediated transcription factor under oxidative stress.
2017-09-11 | PXD005660 | Pride
Project description:To identify the binding partner of LMO2 for explanation of STAT3 signal-related protein in human glioblastoma
2022-08-11 | PXD028254 | Pride
Project description:LMO2 is an oncogenic transcription factor that is frequently overexpressed due to chromosomal abnormalities in T-cell acute lymphoblastic leukemia (T-ALL). In transgenic mouse models, Lmo2 overexpression causes thymocyte self-renewal resulting in T-cell leukemia with long latency. However, the requirement for Lmo2 for leukemia maintenance is poorly understood. To study this, we developed a Tetracycline-regulated knock-in mouse model that reversibly expresses Lmo2 throughout the haematopoietic system. This led to a specific impairment of T-cell development and the development of self-renewing preleukemic stem cells (pre-LSCs) in the thymus, followed by the development of fully penetrant T-lymphoblastic leukemia resembling human T-ALL. In preleukemic mice, repression of Lmo2 overcame the LMO2-induced thymocyte developmental block, reversed Lmo2-induced gene expression changes and eliminated self-renewing pre-LSCs in vivo. In contrast, overt T-lymphoblastic leukemias arising in this model were either immature, Lmo2-dependent leukemias resembling human ETP-ALL, or mature leukemias which were Lmo2-independent. Genomic analyses identified frequent loss of tumour suppressor genes in Lmo2-independent T-ALLs. Deletion of one of these, Ikaros (Ikzf1), was sufficient to transform Lmo2-dependent tumours to Lmo2-independence. Together these results indicate an evolution of oncogene addiction in T-ALL and that loss of Ikaros can promote self-renewal of T-ALL lymphoblasts in the absence of initiating oncogenes.
2020-12-31 | GSE144035 | GEO
Project description:LMO2 regulates gene expression facilitating the formation of multipartite DNA-binding complexes. In B cells, LMO2 is specifically up-regulated in the Germinal Center (GC) reaction and is expressed in GC-derived non-Hodgkin’s lymphomas. LMO2 is one of the most powerful prognostic indicators in DLBCL patients. However, its function in GC B cells and DLBCL is currently unknown. In the present study we characterized the LMO2 transcriptome and interactome in DLBCL cells. LMO2 regulates genes implicated in kinetochore function, chromosome assembly and mitosis. Overexpression of LMO2 in DLBCL cell lines results in centrosome amplification. In DLBCL, the LMO2 complex contains some of the traditional partners such as LDB1, E2A, HEB, Lyl1, ETO2 and SP1, but not TAL1 or GATA proteins. Furthermore, we identified novel LMO2 interacting partners: ELK1, NFATc1 and LEF-1 proteins. Reporter assays revealed that LMO2 increases transcriptional activity of NFATc1 and decreases transcriptional activity of LEF-1 proteins. Overall, our studies identified a novel LMO2 transcriptome and interactome in DLBCL and provide a platform for future elucidation of LMO2 function in GC B-cells and DLBCL pathogenesis.
2012-07-13 | GSE34576 | GEO
Project description:NANOG is a key stem cell pluripotency factor. NANOG’s unique ability to form prion-like assemblies provides a cooperative and concerted DNA bridging mechanism essential for chromatin reorganization and dose-sensitive activation of ground state pluripotency. We take advantage of Hi-C and ChIP-seq experiments to directly address whether NANOG can bridge DNA elements together in human cells, and our results support this.
2022-02-15 | GSE190567 | GEO
Project description:LMO2 regulates gene expression facilitating the formation of multipartite DNA-binding complexes. In B cells, LMO2 is specifically up-regulated in the Germinal Center (GC) reaction and is expressed in GC-derived non-Hodgkin’s lymphomas. LMO2 is one of the most powerful prognostic indicators in DLBCL patients. However, its function in GC B cells and DLBCL is currently unknown. In the present study we characterized the LMO2 transcriptome and interactome in DLBCL cells. LMO2 regulates genes implicated in kinetochore function, chromosome assembly and mitosis. Overexpression of LMO2 in DLBCL cell lines results in centrosome amplification. In DLBCL, the LMO2 complex contains some of the traditional partners such as LDB1, E2A, HEB, Lyl1, ETO2 and SP1, but not TAL1 or GATA proteins. Furthermore, we identified novel LMO2 interacting partners: ELK1, NFATc1 and LEF-1 proteins. Reporter assays revealed that LMO2 increases transcriptional activity of NFATc1 and decreases transcriptional activity of LEF-1 proteins. Overall, our studies identified a novel LMO2 transcriptome and interactome in DLBCL and provide a platform for future elucidation of LMO2 function in GC B-cells and DLBCL pathogenesis. RCK8 DLBCL cell lines were stably transfected with control plasmid or plasmid+LMO2
2012-07-12 | E-GEOD-34576 | biostudies-arrayexpress
Project description:Lmo2 is dispensable for maintenance of most Lmo2-induced murine T-cell leukemias
| PRJNA517144 | ENA
Project description:To understand the changes in the expression of genes in U87MG cells due to LMO2, we analyzed the transcriptome of U87MG cells overexpressing LMO2. As a result, we identify differentially expressed genes patterns so that the signaling mechanism regulated by LMO2 in GBM and changes in cells were observed. These RNA sequencing analysis results enable an understanding of the signaling mechanism by LMO2 in GBM.
2022-07-13 | GSE182169 | GEO