Affinage

EBF1

Transcription factor COE1 · UniProt Q9UH73

Length
591 aa
Mass
64.5 kDa
Annotated
2026-04-28
100 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EBF1 is a pioneer transcription factor that orchestrates B lymphocyte lineage specification, commitment, and maintenance while also regulating adipogenesis, osteoblast-adipocyte balance, and mesenchymal stromal cell function. Its DNA-binding domain adopts a pseudoimmunoglobulin/Rel-homology-like fold with a unique zinc knuckle, and a C-terminal prion-like domain mediates liquid-liquid phase separation with FUS and recruitment of the Brg1 chromatin remodeler, enabling EBF1 to open naive chromatin, initiate DNA demethylation, and establish de novo regulatory landscapes at previously inaccessible genomic sites (PMID:20876732, PMID:33159853, PMID:26982363, PMID:19549820). Operating downstream of IL-7R/STAT5 and E2A, EBF1 directly activates Pax5, Foxo1, surrogate light-chain genes, and Myc while repressing alternative-lineage determinants (Id2, Id3, TCF-1), and it engages in a positive feedback circuit with FOXO1 to reinforce B cell identity; conditional deletion in committed pro-B cells causes lineage conversion to innate lymphoid and T cells (PMID:10435576, PMID:23812095, PMID:23213261, PMID:33619557, PMID:19122139). EBF1 also interacts with the CCR4-NOT complex (via His240) to coordinate target gene transcription and mRNA stability, with TET2 to direct DNA demethylation, and serves as a chromatin anchor for EBV EBNA2 at CBF1-independent sites in infected B cells (PMID:27807034, PMID:23863747, PMID:28968461).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1995 High

    Establishing that EBF1 is essential for early B cell differentiation resolved whether this transcription factor, known from olfactory biology, had a required role in lymphopoiesis.

    Evidence Targeted gene disruption in mice showing a block before Ig gene rearrangement

    PMID:7542362

    Open questions at the time
    • Molecular targets downstream of EBF1 in B progenitors were unknown
    • Whether EBF1 functions instructively or permissively was unresolved
  2. 1995 High

    Domain dissection revealed that EBF1 uses a novel zinc coordination motif for DNA binding and a C-terminal HLH-related domain for dimerization, establishing its modular architecture.

    Evidence Mutational and deletion analysis with dimerization and transcriptional activation assays

    PMID:7796816

    Open questions at the time
    • No high-resolution structure was available
    • How EBF1 recognizes chromatin in vivo was unknown
  3. 1999 High

    Identification of Pax5 and surrogate light-chain genes as direct EBF1 targets, together with genetic synergy with E2A, placed EBF1 in the core B-lineage transcriptional hierarchy.

    Evidence EMSA for direct promoter binding, compound Ebf+/−E2a+/− mice, and synergistic activation of λ5/VpreB in Ba/F3 cells

    PMID:10435576 PMID:9252117

    Open questions at the time
    • How EBF1 expression itself was regulated was unknown
    • Whether EBF1 could specify B cell fate instructively was untested
  4. 2003 High

    Gain-of-function experiments showed EBF1 instructs B cell fate at the expense of T, NK, and dendritic cell lineages, establishing it as a lineage-instructive factor rather than merely a permissive one.

    Evidence Retroviral EBF transduction into HSCs followed by bone marrow reconstitution

    PMID:12970188

    Open questions at the time
    • Whether EBF1 could commit cells independently of Pax5 was unknown
    • Mechanisms of alternative lineage suppression were uncharacterized
  5. 2005 High

    Placing EBF1 downstream of IL-7R/STAT5 signaling and showing that EBF1 suppresses Id2/Id3 to liberate E2A activity defined the signaling input and a key effector mechanism for B cell specification.

    Evidence IL-7Rα−/− rescue by retroviral EBF1; overexpression of Id2/Id3 blocking B cell specification

    PMID:15837809 PMID:19122139

    Open questions at the time
    • Whether other signaling pathways converge on EBF1 expression was unknown
    • Direct chromatin-level mechanism of Id2/Id3 repression was not shown
  6. 2008 High

    EBF1 was shown to restrict alternative lineage options and induce Pax5 independently of Pax5 itself, separating EBF1's lineage-commitment function from Pax5-dependent steps and revealing it as a master regulator of B cell identity.

    Evidence Ectopic EBF expression in Pax5−/− progenitors blocking myeloid and T lineage potential in vivo

    PMID:18176567

    Open questions at the time
    • Genome-wide direct targets mediating lineage restriction were unmapped
    • How EBF1 maintained identity after commitment was unknown
  7. 2008 Medium

    Ebf1−/− mice displayed increased osteoblastogenesis and bone marrow adiposity, extending EBF1's function beyond lymphopoiesis to mesenchymal lineage regulation.

    Evidence Ebf1 knockout mouse bone histomorphometry and adipocyte quantification

    PMID:19130908

    Open questions at the time
    • Direct transcriptional targets in bone were not identified
    • Whether EBF1 acts cell-autonomously in osteoblasts was unclear
  8. 2009 High

    Discovery that EBF1 increases chromatin accessibility and initiates DNA demethylation at the mb-1 promoter, requiring SWI/SNF ATPases Brg1/Brm, provided the first evidence for EBF1's pioneer-like chromatin remodeling function.

    Evidence Conditional EBF:ER activation, shRNA knockdown of Brg1/Brm and Mi-2β, DNA methylation and accessibility assays

    PMID:19549820

    Open questions at the time
    • Whether pioneering activity was genome-wide or locus-specific was unknown
    • The EBF1 domain required for chromatin opening was unidentified
  9. 2010 High

    Crystal structures revealed that EBF1's DNA-binding domain adopts a Rel-homology-like fold with a unique zinc knuckle, resolving its structural classification and explaining its palindromic DNA recognition mechanism.

    Evidence X-ray crystallography of EBF1:DNA complex and domain modules

    PMID:20592035 PMID:20876732

    Open questions at the time
    • Structure of the C-terminal pioneering domain was unsolved
    • How dimerization integrates with chromatin binding in vivo was unclear
  10. 2012 High

    Conditional knockout studies and genome-wide binding analyses established that EBF1 is continuously required beyond specification—for pro-B cell proliferation, survival (via c-Myb, Bcl-xL), BCR/BAFF-R signaling, germinal center formation, and maintenance of B cell identity (preventing conversion to ILCs and T cells).

    Evidence Conditional Ebf1 deletion at multiple stages, ChIP-seq, RNA-seq, forced expression rescue, transfer into alymphoid hosts

    PMID:22431510 PMID:23812095

    Open questions at the time
    • The specific chromatin mechanisms maintaining identity were not resolved
    • Whether EBF1 functions continuously or is needed only at transitions was debated
  11. 2012 High

    Demonstration that EBF1 and FOXO1 operate in a mutual positive feedback circuit, with shared genome-wide target occupancy, explained how B cell identity is reinforced through intergenic transcriptional amplification.

    Evidence Reciprocal depletion in LY6D+ CLPs plus genome-wide ChIP-seq

    PMID:23213261

    Open questions at the time
    • Whether other factors participate in this circuit was unknown
    • Kinetics of the feedback loop during development were uncharacterized
  12. 2016 High

    Mapping the C-terminal domain as the element conferring pioneer function—enabling binding and chromatin opening at naive, inaccessible sites—separated EBF1's pioneering from its conventional transcriptional activation roles.

    Evidence Genome-wide DNaseI-seq and methylation analysis comparing EBF1 wild-type vs. ΔCTD reconstitution in Ebf1−/− progenitors

    PMID:26982363

    Open questions at the time
    • Molecular mechanism by which the CTD opens chromatin was unknown
    • Whether CTD activity depended on co-factors was unresolved
  13. 2016 High

    Identification of the CCR4-NOT complex as an EBF1 partner (via His240) revealed a dual transcription/mRNA-stability regulatory axis, explaining how EBF1 coordinates gene expression at multiple levels.

    Evidence SILAC proteomics, EBF1-H240A complementation, conditional Cnot3 knockout, RNA-seq and ChIP-seq

    PMID:27807034

    Open questions at the time
    • Which specific mRNAs are stabilized by EBF1-CCR4-NOT was not comprehensively mapped
    • Whether this interaction is B-cell-specific was unknown
  14. 2018 High

    Time-resolved genomic analysis confirmed EBF1 occupancy precedes chromatin opening genome-wide and showed transient EBF1 binding at lineage-inappropriate genes precedes their silencing, defining the temporal logic of pioneer activity.

    Evidence Inducible EBF1 in Ebf1−/− pre-pro-B cells with time-resolved ChIP-seq and ATAC-seq

    PMID:29440261

    Open questions at the time
    • How transient binding leads to silencing rather than activation was mechanistically unclear
    • Whether the kinetics differ at individual loci was unexplored
  15. 2020 High

    Discovery that the C-terminal prion-like domain mediates liquid-liquid phase separation with FUS and recruits Brg1, and that heterologous PLDs can substitute, provided a biophysical mechanism for EBF1's pioneering chromatin remodeling function.

    Evidence In vitro phase separation assays, Co-IP of EBF1-FUS and EBF1-Brg1, live imaging, domain swap with heterologous PLDs, ChIP-seq

    PMID:33159853

    Open questions at the time
    • In vivo relevance of phase separation condensates at endogenous loci was not fully established
    • Whether FUS is required for EBF1 pioneering in physiological B cell development was untested
  16. 2022 High

    EBF1 was shown to be exploited by EBV (via EBNA2's α1-helix) and to function as a genome-organizing factor whose nuclear repositioning in T-ALL drives widespread chromatin topology changes and therapy resistance, expanding EBF1's roles to viral pathogenesis and epigenetic adaptation in cancer.

    Evidence EBV Δα1 mutant with Co-IP and RNA-seq; Hi-C, ChIP-seq, ATAC-seq, and nuclear positioning imaging in therapy-resistant T-ALL

    PMID:35182476 PMID:35857872

    Open questions at the time
    • Whether EBF1 nuclear repositioning is a driver or consequence of resistance remains debated
    • Structural basis of EBF1-EBNA2 interaction at atomic resolution is lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the CTD/prion-like domain, the in vivo relevance of phase-separated condensates at endogenous loci during normal B cell development, and how EBF1's diverse tissue-specific functions (B cells, adipocytes, bone, pericytes, stroma) are differentially regulated.
  • No atomic-resolution structure of the CTD/PLD exists
  • Whether phase separation is required in vivo during physiological development is untested
  • Tissue-specific co-factor requirements and post-translational modifications are incompletely cataloged

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11 GO:0003677 DNA binding 8 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-168256 Immune System 8 R-HSA-1266738 Developmental Biology 5 R-HSA-4839726 Chromatin organization 5
Partners
BRG1E2AEBNA2FOXO1FUSPAX5TET2ZFP521
Complex memberships
CCR4-NOT complex (via CNOT3)

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 EBF (EBF1) is required for B cell differentiation; targeted gene disruption in mice blocks generation of immunoglobulin-expressing B cells at a stage before Ig gene rearrangement but after commitment to the B-lymphoid lineage, while non-lymphoid tissues expressing EBF (including olfactory neurons) are unaffected. Targeted gene disruption in mice (knockout), flow cytometry, immunological assays Nature High 7542362
1995 EBF contains a novel zinc coordination motif (H-X3-C-X2-C-X5-C) in its DNA-binding domain critical for DNA recognition, a C-terminal helix-loop-helix-related dimerization domain, and a serine/threonine-rich transcriptional activation domain; the DNA-binding domain alone is monomeric but can mediate dimer assembly on correctly spaced half-sites. Mutational analysis, deletion analysis, dimerization assays, heterologous domain transfer, transcriptional activation assays The EMBO journal High 7796816
1997 EBF and E47 synergize to induce expression of endogenous immunoglobulin surrogate light chain genes (lambda5 and VpreB) in hematopoietic Ba/F3 cells; multiple functional EBF and E47 binding sites were identified in the lambda5 promoter/enhancer, establishing lambda5 as a direct transcriptional target. Stable transfection of cDNAs into Ba/F3 cells, EMSA, promoter/enhancer binding site analysis, gene expression assays Immunity High 9252117
1999 EBF directly binds and activates the Pax5 promoter; EBF and E2A collaborate genetically in regulating B lymphopoiesis, and compound Ebf+/- E2a+/- mice show a marked pro-B cell differentiation defect with reduced expression of Pax5, Rag1, Rag2, and mb-1. Genetic compound heterozygous mouse model, EMSA for direct promoter binding, gene expression analysis Immunity High 10435576
2000 EBF (but not E2A) promotes VlambdaIII-Jlambda1 recombination in non-lymphoid cells; either E2A or EBF can activate IgH DH-JH recombination; EBF acts in concert with the V(D)J recombinase to generate a diverse Ig repertoire, and E2A's transactivation domains are required for IgK VJ recombination. Transfection of non-lymphoid embryonic kidney cells with E2A, EBF, RAG1, RAG2; PCR-based recombination assays Molecular cell High 10882075
2002 The EBF gene promoter is directly activated by E47 (E-protein binding) and by EBF itself (autoregulatory loop); a tissue-restricted factor also binds an upstream regulatory region in B-lineage cells. Promoter identification, primer extension, transient transfection reporter assays, EMSA Journal of immunology Medium 12077253
2003 Enforced EBF expression in hematopoietic stem cells restricts lymphopoiesis to the B cell lineage, causing near-complete absence of T lymphocytes, NK cells, and lymphoid-derived dendritic cells, demonstrating an instructive role in B cell fate specification. Retroviral transduction of EBF into hematopoietic progenitors, bone marrow reconstitution in mice, flow cytometry The EMBO journal High 12970188
2003 CD40-mediated B cell activation induces APE/Ref-1 nuclear translocation, which modulates the DNA-binding activity of EBF; Pax5a physically interacts with EBF and enhances EBF DNA-binding activity to its consensus sequence, and APE/Ref-1 may directly regulate EBF functional activity. CD40 cross-linking, EMSA, co-immunoprecipitation, reporter assay (blk promoter) The Journal of biological chemistry Medium 14594818
2005 Notch1 intracellular domain (Notch1-IC) inhibits EBF DNA-binding activity and down-regulates EBF-regulated promoters in B cells; ligand-induced Notch signaling (Delta4) mimics this effect, revealing that Notch signaling restricts B cell development in part by targeting EBF function. Transient transfection of Notch1-IC, reporter assays, EMSA for DNA binding, endogenous Notch ligand stimulation Blood Medium 15920012
2005 IL-7 receptor signaling promotes B cell development by upregulating EBF1 expression through STAT5 activation; enforced EBF1 expression partially rescues B cell development in IL-7Rα-/- mice, placing EBF1 downstream of IL-7R/STAT5 in the B lymphopoiesis transcription factor network. IL-7 knockout and IL-7Rα knockout mice, STAT5 activation, retroviral EBF rescue experiments, flow cytometry The Journal of experimental medicine High 15837809
2006 Ebf1 directly activates the PPARgamma1 promoter and directly binds and activates the C/EBPalpha promoter; Ebf1 is induced by C/EBPbeta and delta, which bind and activate its promoter; Ebf1 is placed within the known adipogenic transcriptional cascade, and shRNA knockdown of Ebf1 and Ebf2 blocks 3T3-L1 differentiation. Promoter reporter assays, chromatin immunoprecipitation, shRNA knockdown, adipogenesis assays in NIH 3T3 and 3T3-L1 cells Molecular and cellular biology High 17060461
2008 EBF1 is essential for B-lineage priming in common lymphoid progenitors (CLPs); EBF1-deficient CLPs lack B-lineage gene transcription and show reduced IgH rearrangement; Pax5, Pou2af1 (OcaB), and FoxO1 promoters contain functional EBF1 binding sites, establishing them as direct EBF1 targets. Fetal liver transplantation, flow cytometry, EMSA for promoter binding, gene expression analysis in EBF1-deficient CLPs Journal of immunology High 18714008
2008 EBF can restrict alternative lineage options (myeloid, T) and promote B cell fate commitment independently of Pax5; EBF induces Pax5 and antagonizes expression of C/EBPalpha, PU.1, and Id2; sustained EBF expression in Pax5-/- hematopoietic progenitors blocks myeloid and T lineage potential in vivo. Ectopic EBF expression in multipotential progenitors, in vivo transplantation, Pax5-/- genetic background experiments, gene expression analysis Nature immunology High 18176567
2009 EBF1 reprograms mb-1 (Ig-alpha) promoters by increasing chromatin accessibility and initiating DNA demethylation; SWI/SNF ATPases Brg1 and Brm are required for EBF-mediated transcriptional activation (knockdown inhibits activation), whereas Mi-2/NuRD (Mi-2beta knockdown) opposes EBF by maintaining hypermethylated chromatin; EBF and Pax5 together are required for efficient DNA demethylation. Conditional EBF:ER and Pax5:ER fusion activation, shRNA knockdown of chromatin remodeling components, chromatin accessibility assays, DNA methylation analysis Proceedings of the National Academy of Sciences of the United States of America High 19549820
2009 Enforced Ebf1 expression in IL-7Rα-/- bone marrow potently down-regulates Id2 and Id3 mRNA and restores B cell differentiation; overexpression of either Id2 or Id3 blocks B cell specification at the prepro-B cell stage, indicating that Ebf1 specifies B cell fate by suppressing Id2/Id3 and thereby increasing E47 activity post-translationally. Retroviral overexpression of Ebf1, Id2, Id3 in bone marrow, in vivo transplantation, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 19122139
2010 Crystal structure of an Ebf1 dimer bound to its palindromic DNA recognition site reveals a pseudoimmunoglobulin-like fold with novel topology but structural similarity to Rel homology domains of NFAT and NF-κB; DNA contact is made via two loop-based modules and a unique Zn coordination motif, with each Ebf1 monomer interacting with both palindromic half-sites. X-ray crystallography of Ebf1:DNA complex Genes & development High 20876732
2010 Crystal structures of EBF domain modules reveal that the DNA-binding domain resembles the Rel homology superfamily and contains a unique zinc knuckle; EBF proteins also contain an IPT/TIG domain and an atypical helix-loop-helix domain with a novel dimerization motif. X-ray crystallography of structured EBF domain modules The Journal of biological chemistry High 20592035
2010 E2A and EBF1 bind regulatory elements in the Foxo1 locus; E2A, EBF1, and Foxo1 are wired together by cis-regulatory sequences; E2A occupancy promotes H3K4 monomethylation at putative enhancer regions, and these associations are dynamic during developmental progression. ChIP-sequencing, genome-wide binding analysis, histone modification mapping in pro-B cells Nature immunology High 20543837
2012 Conditional inactivation of Ebf1 reveals it is required for proliferation, survival, and signaling of pro-B cells and peripheral B cell subsets; Ebf1 targets c-Myb and Bcl-xL (forced expression rescues survival); Ebf1 deficiency impairs BAFF-R- and BCR-dependent Akt signaling in mature B cells; Ebf1 is also required for germinal center formation and class switch recombination. Conditional Ebf1 knockout, v-Abl transformation rescue, forced expression of targets, genome-wide ChIP and RNA-seq, B cell receptor signaling assays Genes & development High 22431510
2012 Runx1-Cbfβ complexes bind the Ebf1 proximal promoter (Runx-binding motifs required for reporter expression), and Runx1 deficiency leads to increased repressive H3K27 trimethylation at the Ebf1 promoter; retroviral Ebf1 (but not Pax5) restores B cell development in Runx1-deficient progenitors. Conditional Runx1/Cbfβ deletion, ChIP for Runx1-Cbfβ at Ebf1 promoter, histone modification ChIP, retroviral rescue The Journal of experimental medicine High 22665574
2013 EBF1 is required for B cell identity maintenance in committed pro-B cells; conditional deletion of Ebf1 after transfer causes lineage conversion to innate lymphoid cells and T cells; EBF1 directly binds and represses genes encoding Id2 and TCF-1 to prevent alternative lineage fates. Conditional Ebf1 deletion in committed pro-B cells, transfer into alymphoid mice, gene expression analysis, ChIP for EBF1 target binding Nature immunology High 23812095
2013 EBF1 interacts with TET2 as identified by analysis of sequence motifs surrounding hypermethylated sites in IDH-mutant cancers; this interaction was validated by chromatin immunoprecipitation and western blotting, suggesting EBF1 provides sequence-specific targeting for TET2-mediated DNA demethylation. Meta-analysis of methylation data, motif analysis, ChIP, western blotting for EBF1-TET2 interaction Nature communications Medium 23863747
2013 EBF1 directly regulates components of metabolic and inflammatory signaling pathways in mature adipocytes including PI3K/AKT, MAPK, and STAT1 signaling; EBF1 occupies ~35,000 sites in adipocytes, predominantly at enhancers; knockdown reduces insulin-stimulated glucose uptake and lipogenesis. Transcriptional profiling of EBF1-deficient adipocytes, genome-wide EBF1 ChIP-sequencing, functional signaling assays The Journal of biological chemistry High 24174531
2013 Zfp521 interacts with EBF1 protein and represses its transcriptional activity; in bone, Zfp521 knockout leads to increased EBF1 activity in osteoblasts and osteoclasts, and the bone phenotype of Zfp521+/- mice is rescued in Zfp521+/-:Ebf1+/- mice, placing Zfp521 as an upstream repressor of EBF1 in bone homeostasis. Co-immunoprecipitation (Zfp521-EBF1 interaction), compound heterozygous mouse genetic rescue, conditional knockout, in vivo bone phenotyping The Journal of experimental medicine High 23569325
2013 Ebf1 directly targets and represses Rag transcription downstream of STAT5/IL-7R signaling by negatively regulating Foxo1 binding to the Rag locus; Ebf1 achieves this through direct negative regulation of Foxo1 expression and positive regulation of Gfi1b expression; c-Myb acts downstream of Ebf1 in this repression. shRNA knockdown of Ebf1 and c-Myb, ChIP analysis of Foxo1 binding at Rag locus, gene expression analysis in Abl-transformed B cells Journal of immunology Medium 24068669
2014 Ebf1 binds directly to the Atp2a1 (Serca1) promoter and synergizes with MyoD to induce Atp2a1 expression in skeletal muscle; loss of Ebf3 (the closely related family member expressed in diaphragm) impairs Serca1 expression and Ca2+ efflux-related muscle function. Direct promoter binding assay (ChIP), transient transfection/reporter assays, Ebf3 knockout mice, transgenic rescue with Serca1 Nature communications Medium 24786561
2016 The C-terminal domain (CTD) of EBF1 confers pioneering function by promoting chromatin accessibility and DNA demethylation at previously naive (inaccessible) genomic regions; CTD allows EBF1 to bind inaccessible regions that offer limited co-occupancy by other transcription factors, whereas it is dispensable for binding at regions occupied by multiple transcription factors. Genome-wide DNaseI hypersensitivity, DNA methylation analysis, ChIP-seq in Ebf1-/- progenitors with EBF1wt vs. EBF1ΔC reconstitution Immunity High 26982363
2016 CCR4-NOT complex component CNOT3 interacts with EBF1 (histidine 240 in EBF1 critical for this interaction); EBF1-CCR4-NOT interaction regulates specific EBF1 target gene transcription and mRNA stability; EBF1H240A mutation causes partial pro-B cell differentiation block and altered occupancy/expression of specific target genes; conditional Cnot3 inactivation recapitulates the block and impairs EBF1 autoregulation. SILAC mass spectrometry of EBF1-associated proteins, EBF1H240A complementation, RNA-seq, ChIP-seq, conditional Cnot3 knockout Genes & development High 27807034
2016 MEF2C co-regulates B cell-specific transcription with EBF1 at a shared subset of genomic targets; the p38 MAPK pathway activates MEF2C to drive B cell differentiation; MEF2C interacts with HDAC7 to repress the myeloid transcription program. Genome-wide ChIP-seq of MEF2C and EBF1, Mef2c knockout mice, Co-IP for MEF2C-HDAC7 interaction, gene expression analysis PLoS genetics Medium 26900922
2017 EBF1 binds to EBNA2 (Epstein-Barr virus nuclear antigen 2) via its N-terminal domain, serving as a sequence-specific chromatin anchor for EBNA2 at CBF1-independent binding sites in B cells; EBF1 is required for EBNA2 binding at these sites. CBF1-deficient B cells, ChIP-seq of EBNA2, EBF1 motif enrichment analysis, co-immunoprecipitation of EBF1-EBNA2 PLoS pathogens High 28968461
2018 Time-resolved analysis shows EBF1 occupancy precedes formation of chromatin accessibility (pioneer function); transient EBF1 occupancy at lineage-inappropriate genes precedes their silencing; continuous EBF1 function is required for Cd79a promoter activity and maintenance of accessible chromatin permissive for other transcription factor binding. Inducible EBF1 expression in Ebf1-/- pre-pro-B cells, time-resolved ChIP-seq, ATAC-seq, gene expression analysis Genes & development High 29440261
2020 The C-terminal domain (CTD) of EBF1 harbors a prion-like domain (PLD) capable of liquid-liquid phase separation; EBF1 interacts with the RNA-binding protein FUS to enhance phase separation; EBF1 recruits Brg1 (chromatin remodeler) via the CTD; phase separation ability enables pioneering function (chromatin opening) and B-lineage programming; heterologous PLDs confer pioneering function on EBF1ΔCTD. Phase separation assays (liquid-liquid condensate formation), Co-immunoprecipitation of EBF1-FUS and EBF1-Brg1, live imaging of condensates in pro-B cells, domain swap experiments with heterologous PLDs, ChIP-seq Immunity High 33159853
2020 Conditional deletion of Ebf1 in bone marrow mesenchymal stromal cells (CAR cells, PαS cells) impairs HSC adhesion, reduces HSC quiescence, and diminishes myeloid output; EBF1-deficient stroma alters chromatin structure and gene expression (including reduced adhesion-related genes), and changes in HSCs persist in serial transplantations. Conditional Ebf1 deletion in MSCs, single-cell analysis, ATAC-seq, serial transplantation, HSC adhesion assays Nature immunology High 32066955
2021 EBF1 directly controls Myc expression via six EBF1-responsive enhancer elements in the Myc locus; CRISPR-Cas9 targeting of EBF1 binding sites identifies one element critical for Myc expression and pro-B cell expansion; PAX5 also occupies regulatory elements in the Myc locus but acts in opposition to EBF1 to regulate Myc levels. Chromosome conformation analysis (3C), ATAC-seq, ChIP-seq, reporter assays, CRISPR-Cas9 mutagenesis of enhancer elements, ectopic expression experiments Blood High 33619557
2022 EBF1 forms a transcriptional complex with HIF1α in triple-negative breast cancer cells and suppresses p300 activity to fine-tune HIF1α target gene expression, thereby preventing extensive mitophagy-induced cell death; EBF1 depletion induces mitophagy and inhibits tumor growth. Co-immunoprecipitation of EBF1-HIF1α complex, genome-wide mapping of EBF1 transcriptional regulatory network, EBF1 knockdown/knockout, p300 activity assays, mitophagy measurement Proceedings of the National Academy of Sciences of the United States of America Medium 35867755
2022 EBNA2 exploits EBF1 via its N-terminal dimerization (END) domain α1-helix for binding; EBNA2-EBF1 complexes promote MYC expression and metabolic processes driving S-phase progression in EBV-infected B cells; EBV mutants lacking the α1-helix fail to complete early S phase and show impaired MYC and E2F target expression. EBV mutant lacking α1-helix (EBVΔα1), Co-immunoprecipitation, RNA-seq, cell cycle analysis in infected B cells Proceedings of the National Academy of Sciences of the United States of America High 35857872
2022 EBF1 repositioning from the heterochromatic nuclear envelope to the euchromatic interior in therapy-resistant T-ALL cells instructs widespread genome refolding (compartment changes, domain boundary alterations, enhancer repositioning) that promotes therapy resistance; EBF1 derepression drives epigenetic adaptation in leukemic T cells. Hi-C, ChIP-seq, ATAC-seq, imaging of EBF1 nuclear positioning, integration of chromatin organization data in sensitive vs. resistant T-ALL Molecular cell High 35182476
2012 EBF1 and FOXO1 operate in a positive intergenic feedback circuitry: EBF1 depletion in LY6D+ CLPs severely reduces FOXO1 mRNA, while FOXO1 depletion ablates EBF1 transcript levels; genome-wide occupancy shows shared target gene sets. EBF1 and FOXO1 depletion experiments in LY6D+ CLPs, transcription signatures, genome-wide ChIP-seq Proceedings of the National Academy of Sciences of the United States of America High 23213261
2008 Ebf1 plays a role in regulating osteoblast and adipocyte development in vivo; Ebf1-/- mice show increased osteoblastogenesis (increased OB numbers, osteoid volume, bone formation rate, serum osteocalcin) and dramatic increase in bone marrow adipocyte numbers, establishing Ebf1 as a regulator of both osteoblast and adipocyte lineages from mesenchymal progenitors. Ebf1-/- mouse bone phenotyping (histomorphometry, serum markers), bone marrow adipocyte quantification, in vitro osteoclast assays Bone Medium 19130908
2021 EBF1 is expressed in pericytes; EBF1 silencing in human brain vascular pericytes significantly reduces expression of PDGFRβ, CD146, VEGF, angiopoietin-1, NG2, and TGF-β, indicating a functional role for EBF1 in pericyte cell fate commitment. Immunohistochemistry, RT-qPCR, FACS, EBF1 siRNA knockdown in human brain vascular pericytes Histochemistry and cell biology Medium 34272603

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Plant responses to ethylene gas are mediated by SCF(EBF1/EBF2)-dependent proteolysis of EIN3 transcription factor. Cell 628 14675532
1995 Failure of B-cell differentiation in mice lacking the transcription factor EBF. Nature 539 7542362
2003 EIN3-dependent regulation of plant ethylene hormone signaling by two arabidopsis F box proteins: EBF1 and EBF2. Cell 512 14675533
2010 A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate. Nature immunology 410 20543837
1999 Coordinate regulation of B cell differentiation by the transcription factors EBF and E2A. Immunity 250 10435576
1997 EBF and E47 collaborate to induce expression of the endogenous immunoglobulin surrogate light chain genes. Immunity 205 9252117
2008 Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5. Nature immunology 200 18176567
1996 Role of Olf-1 and Pax-6 transcription factors in neurodevelopment. The Journal of neuroscience : the official journal of the Society for Neuroscience 192 8756438
1998 Induction of early B cell factor (EBF) and multiple B lineage genes by the basic helix-loop-helix transcription factor E12. The Journal of experimental medicine 190 9705952
2006 Critical role for Ebf1 and Ebf2 in the adipogenic transcriptional cascade. Molecular and cellular biology 182 17060461
2005 IL-7 receptor signaling is necessary for stage transition in adult B cell development through up-regulation of EBF. The Journal of experimental medicine 180 15837809
1997 The characterization of the Olf-1/EBF-like HLH transcription factor family: implications in olfactory gene regulation and neuronal development. The Journal of neuroscience : the official journal of the Society for Neuroscience 180 9151732
1999 Ebf1 controls early cell differentiation in the embryonic striatum. Development (Cambridge, England) 172 10556054
2013 Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells. Nature immunology 167 23812095
2004 Cellular immune response to parasitization in Drosophila requires the EBF orthologue collier. PLoS biology 161 15314643
2000 E2A and EBF act in synergy with the V(D)J recombinase to generate a diverse immunoglobulin repertoire in nonlymphoid cells. Molecular cell 154 10882075
1997 Family of Ebf/Olf-1-related genes potentially involved in neuronal differentiation and regional specification in the central nervous system. Developmental dynamics : an official publication of the American Association of Anatomists 148 9389446
2013 Meta-analysis of IDH-mutant cancers identifies EBF1 as an interaction partner for TET2. Nature communications 140 23863747
2012 Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells. Genes & development 135 22431510
2011 Ebf1 or Pax5 haploinsufficiency synergizes with STAT5 activation to initiate acute lymphoblastic leukemia. The Journal of experimental medicine 135 21606506
2001 The COE--Collier/Olf1/EBF--transcription factors: structural conservation and diversity of developmental functions. Mechanisms of development 120 11578857
2003 Ebf gene function is required for coupling neuronal differentiation and cell cycle exit. Development (Cambridge, England) 119 14573522
1995 EBF contains a novel zinc coordination motif and multiple dimerization and transcriptional activation domains. The EMBO journal 119 7796816
2015 Seedlings Transduce the Depth and Mechanical Pressure of Covering Soil Using COP1 and Ethylene to Regulate EBF1/EBF2 for Soil Emergence. Current biology : CB 118 26748855
2006 ETHYLENE-INSENSITIVE5 encodes a 5'-->3' exoribonuclease required for regulation of the EIN3-targeting F-box proteins EBF1/2. Proceedings of the National Academy of Sciences of the United States of America 116 16920797
2009 Opposing effects of SWI/SNF and Mi-2/NuRD chromatin remodeling complexes on epigenetic reprogramming by EBF and Pax5. Proceedings of the National Academy of Sciences of the United States of America 114 19549820
2008 EBF1 is essential for B-lineage priming and establishment of a transcription factor network in common lymphoid progenitors. Journal of immunology (Baltimore, Md. : 1950) 113 18714008
2016 EBF1-PDGFRB fusion in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL): genetic profile and clinical implications. Blood 106 26872634
2012 Essential role of EBF1 in the generation and function of distinct mature B cell types. The Journal of experimental medicine 106 22473956
2017 Light-Dependent Degradation of PIF3 by SCFEBF1/2 Promotes a Photomorphogenic Response in Arabidopsis. Current biology : CB 105 28736168
1998 XCoe2, a transcription factor of the Col/Olf-1/EBF family involved in the specification of primary neurons in Xenopus. Current biology : CB 104 9501982
2016 Pioneering Activity of the C-Terminal Domain of EBF1 Shapes the Chromatin Landscape for B Cell Programming. Immunity 101 26982363
2010 Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's syndrome. Genes and immunity 98 20861858
2009 Emerging roles of the EBF family of transcription factors in tumor suppression. Molecular cancer research : MCR 93 19996307
2012 Positive intergenic feedback circuitry, involving EBF1 and FOXO1, orchestrates B-cell fate. Proceedings of the National Academy of Sciences of the United States of America 86 23213261
2014 Collier/OLF/EBF-dependent transcriptional dynamics control pharyngeal muscle specification from primed cardiopharyngeal progenitors. Developmental cell 80 24794633
2018 Dynamic EBF1 occupancy directs sequential epigenetic and transcriptional events in B-cell programming. Genes & development 76 29440261
2008 Ebf1-dependent control of the osteoblast and adipocyte lineages. Bone 74 19130908
2015 Identification of MEF2B, EBF1, and IL6R as Direct Gene Targets of Epstein-Barr Virus (EBV) Nuclear Antigen 1 Critical for EBV-Infected B-Lymphocyte Survival. Journal of virology 71 26468528
2002 Cloning of a novel Olf-1/EBF-like gene, O/E-4, by degenerate oligo-based direct selection. Molecular and cellular neurosciences 71 12139918
2009 Ebf1-mediated down-regulation of Id2 and Id3 is essential for specification of the B cell lineage. Proceedings of the National Academy of Sciences of the United States of America 69 19122139
2003 Enforced expression of EBF in hematopoietic stem cells restricts lymphopoiesis to the B cell lineage. The EMBO journal 66 12970188
2002 Cloning and characterization of a promoter flanking the early B cell factor (EBF) gene indicates roles for E-proteins and autoregulation in the control of EBF expression. Journal of immunology (Baltimore, Md. : 1950) 66 12077253
2019 EBF1-Mediated Upregulation of Ribosome Assembly Factor PNO1 Contributes to Cancer Progression by Negatively Regulating the p53 Signaling Pathway. Cancer research 65 30862720
2011 IL-7 mediates Ebf-1-dependent lineage restriction in early lymphoid progenitors. Blood 65 21652681
2020 A Prion-like Domain in Transcription Factor EBF1 Promotes Phase Separation and Enables B Cell Programming of Progenitor Chromatin. Immunity 64 33159853
2007 Selective expression of Knot/Collier, a transcriptional regulator of the EBF/Olf-1 family, endows the Drosophila sensory system with neuronal class-specific elaborated dendritic patterns. Genes to cells : devoted to molecular & cellular mechanisms 63 17825045
2015 The EBF transcription factor Collier directly promotes Drosophila blood cell progenitor maintenance independently of the niche. Proceedings of the National Academy of Sciences of the United States of America 57 26150488
2012 Lentiviral vector induced insertional haploinsufficiency of Ebf1 causes murine leukemia. Molecular therapy : the journal of the American Society of Gene Therapy 52 22472950
2002 Oscillation between B-lymphoid and myeloid lineages in Myc-induced hematopoietic tumors following spontaneous silencing/reactivation of the EBF/Pax5 pathway. Blood 52 12406913
2005 Inhibition of EBF function by active Notch signaling reveals a novel regulatory pathway in early B-cell development. Blood 50 15920012
2004 Expression of AmphiCoe, an amphioxus COE/EBF gene, in the developing central nervous system and epidermal sensory neurons. Genesis (New York, N.Y. : 2000) 50 14994268
2013 Early B-cell factor-1 (EBF1) is a key regulator of metabolic and inflammatory signaling pathways in mature adipocytes. The Journal of biological chemistry 46 24174531
2012 Runx1-Cbfβ facilitates early B lymphocyte development by regulating expression of Ebf1. The Journal of experimental medicine 46 22665574
2014 Ebf factors and MyoD cooperate to regulate muscle relaxation via Atp2a1. Nature communications 45 24786561
2010 Reduced EBF expression underlies loss of B-cell potential of hematopoietic progenitors with age. Aging cell 45 20331442
2013 A capture-sequencing strategy identifies IRF8, EBF1, and APRIL as novel IGH fusion partners in B-cell lymphoma. Blood 44 23775715
2010 Compound haploinsufficiencies of Ebf1 and Runx1 genes impede B cell lineage progression. Proceedings of the National Academy of Sciences of the United States of America 43 20385820
2022 F-box protein EBF1 and transcription factor ABI5-like regulate banana fruit chilling-induced ripening disorder. Plant physiology 42 34791491
2014 Gene by stress genome-wide interaction analysis and path analysis identify EBF1 as a cardiovascular and metabolic risk gene. European journal of human genetics : EJHG 42 25271088
2010 Structure of an Ebf1:DNA complex reveals unusual DNA recognition and structural homology with Rel proteins. Genes & development 42 20876732
2017 Aryl Hydrocarbon Receptor Activation Suppresses EBF1 and PAX5 and Impairs Human B Lymphopoiesis. Journal of immunology (Baltimore, Md. : 1950) 41 28978690
2013 Coordinated transcriptional regulation of bone homeostasis by Ebf1 and Zfp521 in both mesenchymal and hematopoietic lineages. The Journal of experimental medicine 38 23569325
2005 The UNC-3 Olf/EBF protein represses alternate neuronal programs to specify chemosensory neuron identity. Developmental biology 38 16143323
2003 CD40 stimulation induces Pax5/BSAP and EBF activation through a APE/Ref-1-dependent redox mechanism. The Journal of biological chemistry 38 14594818
2018 Defining B Cell Chromatin: Lessons from EBF1. Trends in genetics : TIG 37 29336845
2015 Combined heterozygous loss of Ebf1 and Pax5 allows for T-lineage conversion of B cell progenitors. The Journal of experimental medicine 37 26056231
2002 Roles of EBF and Pax-5 in B lineage commitment and development. Seminars in immunology 37 12457614
2015 Ebf1 heterozygosity results in increased DNA damage in pro-B cells and their synergistic transformation by Pax5 haploinsufficiency. Blood 36 25838350
2021 The RING E3 ligase SDIR1 destabilizes EBF1/EBF2 and modulates the ethylene response to ambient temperature fluctuations in Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America 35 33526703
2011 EBF proteins participate in transcriptional regulation of Xenopus muscle development. Developmental biology 34 21839736
2016 MEF2C and EBF1 Co-regulate B Cell-Specific Transcription. PLoS genetics 33 26900922
2012 Role of early B-cell factor 1 (EBF1) in Hodgkin lymphoma. Leukemia 33 23174882
2021 EBF1 and PAX5 control pro-B cell expansion via opposing regulation of the Myc gene. Blood 32 33619557
2020 EBF1-deficient bone marrow stroma elicits persistent changes in HSC potential. Nature immunology 32 32066955
2017 Differentiation of human telencephalic progenitor cells into MSNs by inducible expression of Gsx2 and Ebf1. Proceedings of the National Academy of Sciences of the United States of America 32 28137879
2011 A dose-dependent role for EBF1 in repressing non-B-cell-specific genes. European journal of immunology 31 21469119
2011 EBF factors drive expression of multiple classes of target genes governing neuronal development. Neural development 31 21529371
2022 EBNA2-EBF1 complexes promote MYC expression and metabolic processes driving S-phase progression of Epstein-Barr virus-infected B cells. Proceedings of the National Academy of Sciences of the United States of America 29 35857872
2020 TMPO-AS1/miR-98-5p/EBF1 feedback loop contributes to the progression of bladder cancer. The international journal of biochemistry & cell biology 29 32087328
2017 Comprehensive Proteomic Investigation of Ebf1 Heterozygosity in Pro-B Lymphocytes Utilizing Data Independent Acquisition. Journal of proteome research 29 29181981
2002 Impact of targeted vector design on Co/E1 plasmid replication. Trends in biotechnology 29 12007494
2017 EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes in B cells. PLoS pathogens 28 28968461
2013 The Epstein-Barr virus microRNA BART11-5p targets the early B-cell transcription factor EBF1. American journal of blood research 28 23997984
2005 Evi3, a zinc-finger protein related to EBFAZ, regulates EBF activity in B-cell leukemia. Oncogene 28 15580294
2022 EBF1 nuclear repositioning instructs chromatin refolding to promote therapy resistance in T leukemic cells. Molecular cell 27 35182476
2021 EBF1 is expressed in pericytes and contributes to pericyte cell commitment. Histochemistry and cell biology 27 34272603
2016 Rewiring of an ancestral Tbx1/10-Ebf-Mrf network for pharyngeal muscle specification in distinct embryonic lineages. Development (Cambridge, England) 27 27802138
2016 Interaction of CCR4-NOT with EBF1 regulates gene-specific transcription and mRNA stability in B lymphopoiesis. Genes & development 27 27807034
2023 Brassinosteroids promote etiolated apical structures in darkness by amplifying the ethylene response via the EBF-EIN3/PIF3 circuit. The Plant cell 25 36321994
2010 Subtilase cytotoxin induces apoptosis in HeLa cells by mitochondrial permeabilization via activation of Bax/Bak, independent of C/EBF-homologue protein (CHOP), Ire1alpha or JNK signaling. Microbial pathogenesis 25 20561923
2010 Structural determination of functional domains in early B-cell factor (EBF) family of transcription factors reveals similarities to Rel DNA-binding proteins and a novel dimerization motif. The Journal of biological chemistry 25 20592035
2004 Expression patterns of the coe/ebf transcription factor genes during chicken and mouse limb development. Gene expression patterns : GEP 25 15261831
2020 EBF1 and Pax5 safeguard leukemic transformation by limiting IL-7 signaling, Myc expression, and folate metabolism. Genes & development 24 33004416
2017 Deregulation of kinase signaling and lymphoid development in EBF1-PDGFRB ALL leukemogenesis. Leukemia 24 28555080
2015 ZNF423 and ZNF521: EBF1 Antagonists of Potential Relevance in B-Lymphoid Malignancies. BioMed research international 24 26788497
2019 An ancient role for collier/Olf/Ebf (COE)-type transcription factors in axial motor neuron development. Neural development 23 30658714
2013 Ebf1 and c-Myb repress rag transcription downstream of Stat5 during early B cell development. Journal of immunology (Baltimore, Md. : 1950) 23 24068669
2022 EBF1 promotes triple-negative breast cancer progression by surveillance of the HIF1α pathway. Proceedings of the National Academy of Sciences of the United States of America 22 35867755
2020 Long intergenic noncoding RNA 00844 promotes apoptosis and represses proliferation of prostate cancer cells through upregulating GSTP1 by recruiting EBF1. Journal of cellular physiology 22 32329523