Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferative expansion and survival of B cells
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PROVIDER: PRJNA152013 | ENA |
REPOSITORIES: ENA
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Project description:This SuperSeries is composed of the following subset Series: GSE35910: Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferative expansion and survival of B cells [EBF1] GSE35914: Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferative expansion and survival of B cells [H3K4me2 and H3K4me3] Refer to individual Series See related Series GSE36061.
2012-04-02 | E-GEOD-35915 | biostudies-arrayexpress
Project description:Transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into differentiation stage-specific functions of Ebf1, we conditionally inactivated Ebf1. We found that Ebf1 is required for proliferation, survival and signaling of pro-B cells and peripheral B cell subsets. The proliferation defect of Ebf1-deficient pro-B cells, including the impaired expression of IL-7Ra and several cell cycle regulators, is overcome by transformation with v-Abl. The survival defect of transformed Ebf1fl/fl pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-xL. In mature B cells, Ebf1 deficiency interferes with the BAFF-R and BCR-dependent Akt signaling pathways, as well as with germinal center formation and class switch recombination. Genome-wide analyses of Ebf1 binding and Ebf1-mediated gene expression in mature B cells and comparison with reported data sets in pro-B cells provide insight into the basis for lineage- and stage-specific functions of Ebf1. EBF1 binding in splenic B cells in mice
2012-04-02 | E-GEOD-35910 | biostudies-arrayexpress
Project description:Transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into differentiation stage-specific functions of Ebf1, we conditionally inactivated Ebf1. We found that Ebf1 is required for proliferation, survival and signaling of pro-B cells and peripheral B cell subsets. The proliferation defect of Ebf1-deficient pro-B cells, including the impaired expression of IL-7Ra and several cell cycle regulators, is overcome by transformation with v-Abl. The survival defect of transformed Ebf1fl/fl pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-xL. In mature B cells, Ebf1 deficiency interferes with the BAFF-R and BCR-dependent Akt signaling pathways, as well as with germinal center formation and class switch recombination. Genome-wide analyses of Ebf1 binding and Ebf1-mediated gene expression in mature B cells and comparison with reported data sets in pro-B cells provide insight into the basis for lineage- and stage-specific functions of Ebf1.
2012-04-03 | GSE35910 | GEO
Project description:Transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into differentiation stage-specific functions of Ebf1, we conditionally inactivated Ebf1. We found that Ebf1 is required for proliferation, survival and signaling of pro-B cells and peripheral B cell subsets. The proliferation defect of Ebf1-deficient pro-B cells, including the impaired expression of IL-7Ra and several cell cycle regulators, is overcome by transformation with v-Abl. The survival defect of transformed Ebf1fl/fl pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-xL. In mature B cells, Ebf1 deficiency interferes with the BAFF-R and BCR-dependent Akt signaling pathways, as well as with germinal center formation and class switch recombination. Genome-wide analyses of Ebf1 binding and Ebf1-mediated gene expression in mature B cells and comparison with reported data sets in pro-B cells provide insight into the basis for lineage- and stage-specific functions of Ebf1. Localistaion of histone modification (H3K4me2 and H3K4me3) in splenic B cells in mice by ChIP-seq
2012-04-02 | E-GEOD-35914 | biostudies-arrayexpress
Project description:Transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into differentiation stage-specific functions of Ebf1, we conditionally inactivated Ebf1. We found that Ebf1 is required for proliferation, survival and signaling of pro-B cells and peripheral B cell subsets. The proliferation defect of Ebf1-deficient pro-B cells, including the impaired expression of IL-7Ra and several cell cycle regulators, is overcome by transformation with v-Abl. The survival defect of transformed Ebf1fl/fl pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-xL. In mature B cells, Ebf1 deficiency interferes with the BAFF-R and BCR-dependent Akt signaling pathways, as well as with germinal center formation and class switch recombination. Genome-wide analyses of Ebf1 binding and Ebf1-mediated gene expression in mature B cells and comparison with reported data sets in pro-B cells provide insight into the basis for lineage- and stage-specific functions of Ebf1.
2012-04-03 | GSE35914 | GEO
Project description:Lineage restricted transcription factors are frequently found mutated in B-lymphoid leukemia, suggesting a close link between normal and malignant B-cell development. One of these transcription factors is EBF1, a protein of critical importance for specification but also survival of B-lymphoid progenitors. We here report that impaired EBF1 function in mouse B-cell progenitors results in reduced expression of Myc. Ectopic expression of MYC rescued B-cell expansion in the absence of EBF1 both in vivo and in vitro. Using chromosome conformation analysis in combination with ATAC, ChIP-seq and reporter gene assays, identified six EBF responsive enhancer elements that could be annotated to the Myc gene. Crispr-Cas9 mediated targeting of EBF1 binding sites identified one element of importance for Myc expression and pro-B cell expansion providing evidence for that Myc is a direct target for EBF1. Furthermore, ChIP-seq analysis suggested that several regulatory elements in the Myc gene were targeted by PAX5. However, ectopic expression of PAX5 in EBF1 deficient cells was found to induce a cell cycle block and reduce Myc expression suggesting that EBF1 and PAX5 act in an opposing manner at this shared target gene. This hypothesis was further substantiated by the finding that Pax5 inactivation reduced the need for EBF1 in pro-B cell expansion. The binding of EBF1 and PAX5 to regulatory elements in the human MYC gene in a B-ALL cell line indicate that this regulatory loop may be of relevance for our understanding of both normal and malignant B-cell development.
2021-03-05 | GSE159957 | GEO
Project description:Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferative expansion and survival of B cells [EBF1]
| PRJNA155693 | ENA
Project description:EBF1 and PAX5 are two transcription factors targeted in human B-ALL. Their importance for normal B-cell differentiation has led to the suggestion that impaired function of these proteins contributes to the developmental block observed in B-lineage leukemia. However, increased understanding of the function of these proteins has suggested more complex roles in malignant transformation. We here report that the loss of EBF1 function in B-cell progenitors results in reduced expression of c-MYC. Ectopic expression of c-MYC rescues B-cell expansion in the absence of EBF1 both in vivo and in vitro and ChIP-seq analysis identifies multiple binding sites for EBF1 in putative regulatory elements of the mouse c-Myc gene. On the contrary, expression of PAX5 in EBF1 deficient cells resulted in down regulation of c-Myc and inhibition of cell expansion. Since both EBF1 and PAX5 bind multiple regulatory elements in the c-Myc gene, these data suggest that EBF1 and PAX5 have opposing functions with regard to regulation of c-Myc expression. This suggests the existence of a lineage restricted regulatory loop controlling the expansion of B-lineage progenitors. The binding of EBF1 and PAX5 to multiple regulatory elements in the human c-MYC gene indicate that this regulatory loop may be of relevance for our understanding of leukemia formation.
2019-11-30 | GSE136238 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2012-04-03 | GSE35915 | GEO
Project description:Early B cell factor 1 (EBF1) is one of the key transcription factors required for orchestrating B-cell lineage development. Although studies have shown that Ebf1 haploinsufficiency is involved in the development of leukemia, no study has been conducted that characterizes the global effect of Ebf1 heterozygosity on the proteome of pro-B lymphocytes. Here, we employ both DIA (Data Independent Acquisition) and shotgun DDA (Data Dependent Acquisition) workflows for profiling proteins that are differently expressed between Ebf1+/+ and Ebf1+/- cells. Both DDA and DIA were able to reveal the downregulation of the EBF1 transcription factor in Ebf1+/- pro-B lymphocytes. Further examination of differentially expressed proteins by DIA revealed that, similar to EBF1, the expression of other B-cell lineage regulators, such as TCF3 and Pax5, is also down-regulated in Ebf1 heterozygous cells. Functional DIA analysis of differentially expressed proteins showed that EBF1 heterozygosity resulted in the deregulation of at least 8 transcription factors involved in lymphopoiesis, and to the deregulation of key proteins playing crucial roles in survival, development and differentiation of pro-B lymphocytes.
2017-12-20 | PXD008396 | Pride