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Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferative expansion and survival of B cells [EBF1]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE35910 | GEO | 2012/04/03

SECONDARY ACCESSION(S): PRJNA155693

REPOSITORIES: GEO

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Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferative expansion and survival of B cells [EBF1]

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

Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferative expansion and survival of B cells [H3K4me2 and H3K4me3]

2012-04-02 | E-GEOD-35914 | biostudies-arrayexpress

Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferative expansion and survival of B cells [H3K4me2 and H3K4me3]

2012-04-03 | GSE35914 | GEO

A comprehensive Proteomic Investigation of Ebf1 Heterozygosity in pro-B lymphocytes utilizing Data Independent Acquisition

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

Ebf1 ChIP

Project description:Ebf1 is a key determinant of B-lymphocyte specification. In order to identify unknown transcriptional targets, endogenous Ebf1 was isolated by chromatin-IP from primary pro-B cells and the copurified DNA was hybridized to promoter tiling arrays. Ebf1 was ChIPed using a polyclonal antibody directed against an N-terminal peptide from primary pro-B cells grown in the presence of Il7. The resulting DNA was analyzed by tiling array hybridization.

2010-06-24 | E-GEOD-21469 | biostudies-arrayexpress

Gene expression analysis after reconstitution of Ebf1-deficient pre-pro-B cells with Ebf1

Project description:Ebf1 deficient pre-pro B-cells (Fraction A) can be cultured in the presence of stromal feeders and cytokines. The retroviral transduction of these cells with Ebf1 was used as gain-of-function experiment for the analysis of direct and functional target genes of Ebf1. Ebf1 deficient pre-pro B-cells were retrovirally transduced with an Ebf1-expressing or control retrovirus. 24h after transduction the infected cells were isolated and their gene expression profile was compared.

2010-07-29 | E-GEOD-21455 | biostudies-arrayexpress

Essential role of EBF1 in B cell immunity by controlling the generation and function of distinct mature B cell types

Project description:The transcription factor EBF1 is essential for lineage specification in early B cell development. Here we demonstrate by conditional mutagenesis that EBF1 was required for B cell commitment, pro-B cell development and subsequent transition to pre-B cells. Later in B cell development, EBF1 was essential for the generation and maintenance of distinct mature B cell types. Marginal zone and B-1 B cells were lost, whereas follicular and germinal center B cells were reduced in the absence of EBF1. Activation of the B cell receptor resulted in impaired intracellular signaling, proliferation and survival of EBF1-deficient follicular B cells. Immune responses were severely reduced upon Ebf1 inactivation, as germinal centers were formed but not maintained. ChIP- and RNA-sequencing of follicular B cells identified EBF1-activated genes that code for receptors, signal transducers and transcriptional regulators implicated in B cell signaling. Notably, ectopic expression of EBF1 efficiently induced the development of B-1 cells at the expense of conventional B cells. These gain- and loss-of-function analyses uncovered novel important functions of EBF1 in controlling B cell immunity. 29 samples (4 ChIP-seq,16 input, 9 RNA-seq), All ChIP-seq in 2 biological replicates, but EBF1 ChIP-seq Pro-B in 2 technical replicates; All RNA-seq in 2 biological replicates but RNA-seq mature B_FO B_Cd23-Cre Ebf1(fl/–). WT and experimental samples are provided.

2012-03-20 | E-GEOD-35857 | biostudies-arrayexpress

Genome-wide mapping of EBF1 binding sites in murine pre B-cells

Project description:Early B cell factor-1 (Ebf1), a transcription factor expressed in B cells, adipocytes and neuronal cells, has been identified as a determinant in the specification of the B cell lineage in which Ebf1 acts in a regulatory network with the transcription factors E2A and Pax5. To gain insight into the molecular basis of Ebf1 function in early stage B cells, we compared the data set of a genome-wide ChIP sequencing analysis with gain- and loss-of-function transcriptome analyses. Identification of genetic loci enriched by chromatin-immunoprecipitation using antibodies against EBF1.

2010-05-06 | E-GEOD-19971 | biostudies-arrayexpress

Genome-wide occupancy of EBF1-wt & EBF1-H240A

Project description:To study the function of EBF1-H240 residue, genome-wide EBF1 ChIP was performed in A-MuLV transformed pro-B (Ebf1fl/fl;RERTCre) cells transduced with Ebf1wt and Ebf1H240A expressing vectors.

2016-11-21 | GSE87636 | GEO

Dynamic EBF1 occupancy directs sequential epigenetic and transcriptional events in B cell programming [EBF1-ChIP-Seq-Cre]

Project description:EBF1 is essential for B cell specification and commitment. To explore the dynamics of EBF1 initiated B cell programming, we performed EBF1 ChIP-seq, ATAC-seq, bisulfite-seq, RNA-seq and several histone ChIP-seq analyses at different stages of the transition from Ebf1-/- pre-pro-B to pro-B triggered by EBF1 restoration. We also performed Pax5 ChIP-seq in Ebf1-/- pre-pro-B cell and EBF1-restored pro-B cell to study the pioneering function of EBF1 that allows other transcription factors to access certain chromatin sites.

2018-02-20 | GSE107236 | GEO

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