Affinage

EBF1

Transcription factor COE1 · UniProt Q9UH73

Length
591 aa
Mass
64.5 kDa
Annotated
2026-06-09
100 papers in source corpus 44 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EBF1 is a lineage-instructive pioneer transcription factor that specifies and maintains the B lymphocyte program, acting at the earliest committed progenitor stages before immunoglobulin gene rearrangement (PMID:7542362, PMID:18714008). It operates within a transcriptional hierarchy downstream of IL-7R/STAT5 signaling and the E2A protein E12, which induce EBF1 expression, and downstream of Runx1-Cbfβ, which epigenetically activates the Ebf1 promoter (PMID:9705952, PMID:15837809, PMID:22665574); EBF1 in turn sustains its own expression through an autoregulatory loop and wires a positive feedback circuit with FOXO1 (PMID:12077253, PMID:23213261). EBF1 recognizes palindromic DNA sites through a pseudoimmunoglobulin-like/Rel-homology-related DNA-binding domain bearing a unique zinc-coordination motif, dimerizes via an atypical helix-loop-helix domain, and activates transcription through a serine/threonine-rich activation domain (PMID:7796816, PMID:20876732, PMID:20592035). Its pioneer activity resides in a C-terminal prion-like domain that drives liquid-liquid phase separation with FUS and recruits the SWI/SNF remodeler Brg1, enabling EBF1 to open and demethylate previously naive chromatin ahead of accessibility formation (PMID:19549820, PMID:26982363, PMID:29440261, PMID:33159853). Through these mechanisms EBF1 directly activates the B-cell network—Pax5, Foxo1, the surrogate light-chain genes Igll1/Vpreb1, and Myc—and promotes Igh locus accessibility by repressing the cohesin-release factor Wapl, while repressing alternative-lineage determinants including Id2, Id3, and TCF-1, an activity it also coordinates with the CCR4-NOT complex through a direct CNOT3 interaction (PMID:9252117, PMID:10435576, PMID:18714008, PMID:23812095, PMID:27807034, PMID:33619557, PMID:39179932). Loss of EBF1 in committed pro-B cells permits their conversion to T and innate lymphoid cells, and EBF1 additionally controls pro-B proliferation, survival, and BCR/BAFF-R signaling at later developmental stages (PMID:22431510, PMID:23812095, PMID:22473956). Beyond the B lineage, EBF1 governs striatal neuronal differentiation, the osteoblast/adipocyte balance, adipogenesis and adipocyte insulin signaling, bone-marrow stromal support of hematopoietic stem cells, and pericyte commitment, demonstrating broadly redeployed differentiation-control function (PMID:10556054, PMID:17060461, PMID:19130908, PMID:24174531, PMID:32066955).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1995 High

    Established that EBF1 is genetically required for B cell development at a defined stage, fixing its place in the B-lineage hierarchy before immunoglobulin rearrangement.

    Evidence Targeted gene disruption in mice with flow cytometry and gene expression analysis

    PMID:7542362

    Open questions at the time
    • Did not define direct molecular targets
    • Did not establish DNA-binding mechanism
  2. 1995 High

    Defined the modular architecture of EBF1, showing how a novel zinc-coordination DNA-binding domain, an HLH-related dimerization domain, and an activation domain together enable sequence-specific transactivation.

    Evidence Mutational analysis with DNA-binding and transcriptional activation assays using heterologous domain fusions

    PMID:7796816

    Open questions at the time
    • No structural model at this stage
    • C-terminal pioneer/phase-separation function not yet recognized
  3. 1997 High

    Demonstrated that EBF1 directly activates endogenous B-lineage target genes (surrogate light chains) in synergy with E2A, moving beyond requirement to direct gene control.

    Evidence Stable cDNA transfection in Ba/F3 cells with binding-site identification

    PMID:9252117

    Open questions at the time
    • Synergy mechanism with E47 not resolved
    • Chromatin context not assessed
  4. 1998 High

    Placed E2A upstream of EBF1, ordering the transcription factor cascade of B-lineage specification.

    Evidence Ectopic E12 and EBF expression in a macrophage-like line with gene expression analysis

    PMID:9705952

    Open questions at the time
    • Mechanism of E2A-driven Ebf1 induction not defined
    • Did not address feedback architecture
  5. 1999 High

    Identified Pax5 as a direct EBF1 target and demonstrated genetic collaboration between EBF1 and E2A, linking the two factors quantitatively in pro-B differentiation.

    Evidence Compound heterozygous mouse genetics with promoter binding and expression analysis

    PMID:10435576

    Open questions at the time
    • Did not separate EBF1-dependent from Pax5-dependent commitment functions
  6. 1999 High

    Extended EBF1 function beyond hematopoiesis, showing it controls striatal neuronal differentiation, indicating a broadly redeployed differentiation-control role.

    Evidence Knockout mouse with in situ hybridization and histology

    PMID:10556054

    Open questions at the time
    • Direct neuronal targets not identified
    • Mechanistic overlap with B-lineage function unknown
  7. 2003 High

    Showed EBF1 is instructive rather than permissive for B fate, since enforced expression restricts hematopoietic output almost exclusively to B cells.

    Evidence Retroviral transduction of progenitors with transplantation and flow cytometry

    PMID:12970188

    Open questions at the time
    • Did not define the repressive targets enforcing fate restriction
  8. 2005 High

    Positioned IL-7R/STAT5 signaling upstream of EBF1 and showed EBF1 can substitute for IL-7R, integrating cytokine signaling into the transcriptional hierarchy.

    Evidence IL-7 and IL-7Ralpha knockout mice with retroviral EBF rescue and STAT5 experiments

    PMID:12811842 PMID:15837809

    Open questions at the time
    • Quantitative contribution of STAT5 versus other inputs to Ebf1 induction unresolved
  9. 2008 High

    Established EBF1 as a dual activator/repressor that commits cells to B lineage partly independently of Pax5 by antagonizing C/EBPalpha, PU.1, and Id2.

    Evidence Conditional deletion plus ectopic expression with in vivo lineage and expression profiling

    PMID:18176567 PMID:18714008

    Open questions at the time
    • Mechanism of alternative-lineage gene repression not defined at chromatin level
  10. 2009 High

    Revealed the chromatin-reprogramming mechanism: EBF1 increases accessibility and initiates DNA demethylation via SWI/SNF (Brg1/Brm), opposed by Mi-2/NuRD, priming targets for Pax5.

    Evidence Inducible EBF:ER/Pax5:ER systems with shRNA knockdown, accessibility and methylation assays

    PMID:19549820

    Open questions at the time
    • Did not identify the EBF1 domain responsible for pioneering
    • Phase-separation basis not yet known
  11. 2009 High

    Demonstrated that EBF1-mediated repression of Id2 and Id3 is essential for B specification, and identified non-hematopoietic roles in the osteoblast/adipocyte balance and adipogenesis.

    Evidence In vivo rescue with Id overexpression; knockout histomorphometry; promoter activation and knockdown in adipocyte models

    PMID:17060461 PMID:19122139 PMID:19130908

    Open questions at the time
    • Shared versus lineage-specific cofactors across tissues not defined
  12. 2010 High

    Provided high-resolution structural basis for DNA recognition, showing a pseudoimmunoglobulin/Rel-homology-related fold with a unique zinc knuckle and an atypical HLH dimerization motif.

    Evidence X-ray crystallography of the EBF1 dimer-DNA complex and isolated domains

    PMID:20592035 PMID:20876732

    Open questions at the time
    • Structure of the C-terminal/prion-like region not determined
    • Did not address phase separation
  13. 2010 High

    Mapped EBF1 genome-wide in a regulatory network with E2A and Foxo1, linking factor occupancy to enhancer histone marks in pro-B cells.

    Evidence ChIP-seq with genome-wide regulatory element and histone modification analysis

    PMID:20543837

    Open questions at the time
    • Direction of causality among the three factors not fully resolved here
  14. 2011 High

    Defined EBF1 as a positive feedback partner of FOXO1 and a controller of pro-B proliferation, survival, and mature B-cell signaling via direct targets including c-Myb and Bcl-xL.

    Evidence Conditional inactivation, reciprocal depletion, forced target expression, and genome-wide ChIP-seq/RNA analysis

    PMID:22431510 PMID:23213261

    Open questions at the time
    • How the EBF1-FOXO1 loop is initiated remains unresolved
  15. 2012 High

    Showed EBF1 actively maintains commitment, since its loss in committed pro-B cells permits conversion to T and innate lymphoid cells, and identified Runx1-Cbfβ as an upstream epigenetic activator of Ebf1.

    Evidence Conditional deletion with lineage tracing and ChIP; conditional Runx1/Cbfβ deletion with reporter mutagenesis and retroviral rescue

    PMID:22473956 PMID:22665574 PMID:23812095

    Open questions at the time
    • Mechanism keeping alternative-lineage genes silenced after commitment not fully defined
  16. 2013 High

    Identified the CCR4-NOT complex as a direct EBF1 partner (via CNOT3 at His240) coupling EBF1 to mRNA stability and autoregulation, and defined adipocyte-specific genome-wide EBF1 functions in insulin signaling.

    Evidence SILAC mass spectrometry, H240A mutagenesis, conditional Cnot3 knockout; adipocyte ChIP-seq with metabolic assays

    PMID:23569325 PMID:24174531 PMID:27807034

    Open questions at the time
    • How EBF1 directs gene-specific mRNA stability via CCR4-NOT not mechanistically resolved
  17. 2016 High

    Localized pioneer function to the EBF1 C-terminal domain, which is required for de novo accessibility and demethylation at sites with limited co-occupancy by other factors.

    Evidence Genome-wide DNaseI HS, methylation, and ChIP-seq comparing EBF1wt and EBF1ΔC in Ebf1-/- progenitors

    PMID:26982363

    Open questions at the time
    • Biophysical basis of CTD pioneering not yet known at this point
  18. 2018 High

    Demonstrated by time-resolved analysis that EBF1 occupancy precedes accessibility formation, formally establishing pioneer kinetics and a requirement for continuous EBF1 to maintain accessible domains.

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

    PMID:29440261

    Open questions at the time
    • Did not resolve the molecular machinery converting binding to accessibility
  19. 2020 High

    Provided the biophysical mechanism of pioneering: the CTD prion-like domain drives phase separation enhanced by FUS and recruits Brg1 into condensates to stabilize chromatin occupancy.

    Evidence Phase separation assays, FUS/Brg1 Co-IP, live imaging, FRAP, and heterologous PLD rescue

    PMID:32066955 PMID:33159853

    Open questions at the time
    • In vivo relevance of condensate formation at endogenous loci not fully quantified
  20. 2021 High

    Established Myc as a direct EBF1 target driving pro-B expansion through defined enhancers, and extended EBF1 roles to pericyte commitment.

    Evidence Chromosome conformation, ATAC/ChIP-seq, CRISPR-Cas9 enhancer mutagenesis, and rescue; pericyte siRNA knockdown

    PMID:33619557 PMID:34272603

    Open questions at the time
    • Relative contribution of individual Myc enhancers in vivo not fully dissected
  21. 2024 High

    Acute degradation showed EBF1 acts predominantly as an activator inducing open chromatin, with largely unique targets, and revealed it promotes Igh locus loop extrusion by repressing Wapl.

    Evidence In vivo degron-based acute degradation with ATAC-seq, ChIP-seq, and RNA-seq across B-cell stages

    PMID:39179932

    Open questions at the time
    • How EBF1 represses Wapl mechanistically not resolved
    • Stage-specific cofactor switching not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EBF1 condensate formation, cofactor selection (CCR4-NOT, Brg1, FUS), and activator-versus-repressor output are integrated to produce cell-type-specific programs across B cells, adipocytes, neurons, stroma, and tumors remains unresolved.
  • No unified model linking phase separation to gene-specific outcomes
  • Cross-tissue cofactor determinants unknown
  • Mechanism of context-dependent repression incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 3
Localization
GO:0005654 nucleoplasm 3 GO:0005634 nucleus 2
Pathway
R-HSA-4839726 Chromatin organization 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 4
Partners
BRG1/SMARCA4CNOT3E2A/E47FOXO1FUSMEF2CSTAT5ZNF521

Evidence

Reading pass · 44 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 shows EBF-deficient mice lack B cells with rearranged immunoglobulin D and JH gene segments but contain B220+CD43+ progenitor cells, placing EBF function at a stage before Ig gene rearrangement but after B-lymphoid commitment. Targeted gene disruption (knockout mouse), flow cytometry, gene expression analysis 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 can mediate both dimerization on optimized half-sites and transcriptional activation. Mutational analysis, DNA-binding assays, transcriptional activation assays with heterologous domain fusions The EMBO journal High 7796816
1997 EBF and E47 synergize to induce expression of the endogenous immunoglobulin surrogate light chain genes lambda5 and VpreB in Ba/F3 hematopoietic cells; multiple functional EBF and E47 binding sites were identified in the lambda5 promoter/enhancer, establishing lambda5 as a direct genetic target. Stable transfection of cDNAs encoding EBF or E47 into Ba/F3 cells, endogenous gene expression analysis, binding site identification Immunity High 9252117
1998 E2A protein E12 induces EBF expression in a macrophage-like cell line, and EBF alone activates a subset of B lineage genes, placing E2A upstream of EBF in the transcriptional hierarchy of B cell lineage specification. Ectopic expression of E12 and EBF in 70Z/3-derived macrophage line, gene expression analysis The Journal of experimental medicine High 9705952
1999 EBF directly binds and activates the Pax5 promoter; genetic collaboration between EBF and E2A is demonstrated by Ebf+/- E2a+/- compound heterozygous mice showing stronger defects in pro-B cell differentiation than single mutants, with reduced Pax5, Rag1, Rag2, and mb-1 expression. Compound heterozygous mouse genetics, promoter binding assays, gene expression analysis Immunity High 10435576
1999 Ebf1 controls cell differentiation in the murine embryonic striatum; Ebf1 targeted disruption causes failure to downregulate SVZ-restricted genes and failure to activate mantle-specific genes in postmitotic cells, followed by increased cell death and dramatic reduction in postnatal striatum size. Targeted gene disruption (knockout mouse), in situ hybridization, histological analysis Development (Cambridge, England) High 10556054
2000 EBF promotes VlambdaIII-Jlambda1 recombination in non-lymphoid embryonic kidney cells when co-expressed with RAG1/RAG2, while E2A (but not EBF) activates IgK VK1J rearrangement; either E2A or EBF can activate IgH DH4J recombination, demonstrating distinct and partially overlapping roles in V(D)J recombination. Transfection of E2A, EBF, RAG1/RAG2 into embryonic kidney cells, PCR-based detection of recombination products Molecular cell Medium 10882075
2002 The EBF gene promoter contains functional binding sites for E-proteins (E47 activates the promoter) and for EBF itself, establishing an autoregulatory loop; a tissue-restricted factor also binds an upstream regulatory region in B-lineage cells. Primer extension, reporter gene assays, EMSA, transfection assays Journal of immunology Medium 12077253
2003 Enforced expression of EBF in hematopoietic stem cells restricts lymphopoiesis almost exclusively to the B cell lineage at the expense of T cells, NK cells, and lymphoid dendritic cells, demonstrating an instructive role for EBF in B cell fate specification. Retroviral transduction of EBF into hematopoietic progenitors, bone marrow transplantation, flow cytometric analysis The EMBO journal High 12970188
2003 STAT5 (phosphorylated downstream of IL-7 receptor) binds to the EBF-binding site in the Pax5 promoter (SBM) and enhances EBF-mediated transcription of Pax5, providing a direct mechanistic link between IL-7R signaling and Pax5 expression via EBF. Reporter gene assays, EMSA, chromatin immunoprecipitation European journal of immunology Medium 12811842
2005 IL-7 receptor signaling upregulates EBF expression (via STAT5 activation) in pre-pro-B cells, and enforced EBF expression partially rescues B cell development in IL-7Ralpha-/- mice, placing IL-7R signaling upstream of EBF in the transcriptional hierarchy. IL-7 knockout and IL-7Ralpha knockout mouse analysis, retroviral EBF transduction, STAT5 activation experiments, in vivo rescue The Journal of experimental medicine High 15837809
2005 Notch signaling (Notch1-IC or Delta4 ligand-induced) inhibits EBF function by reducing EBF DNA-binding activity, thereby down-regulating EBF-regulated promoters; this provides a mechanism by which Notch promotes T cell fate over B cell fate by targeting both EBF and E2A. Transient transfection of Notch1-IC into pre-B cell line, reporter assays, DNA-binding assays, ligand stimulation of endogenous Notch receptors Blood Medium 15920012
2006 Ebf1 promotes adipogenesis by directly activating the PPARgamma1 promoter and the C/EBPalpha promoter; Ebf1 itself is induced by C/EBPbeta and delta binding its promoter; knockdown of Ebf1 and Ebf2 by shRNA blocks 3T3-L1 differentiation, establishing a critical role for Ebf1 within the adipogenic transcriptional cascade. Overexpression in NIH 3T3 fibroblasts, shRNA knockdown in 3T3-L1 cells, promoter binding assays, reporter assays Molecular and cellular biology High 17060461
2008 EBF restricts alternative lineage options (myeloid, T lineage) and promotes B cell fate commitment independently of Pax5; ectopic EBF in multipotent progenitors directs B cell generation, antagonizes C/EBPalpha, PU.1 and Id2 expression, and sustained EBF expression in Pax5-/- pro-B cells is sufficient to repress myeloid and T lineage genes. Conditional deletion of EBF, ectopic expression in multipotential progenitors, in vivo lineage fate analysis, gene expression profiling Nature immunology High 18176567
2008 EBF1 is required for B-lineage priming in common lymphoid progenitors (CLPs); EBF1-deficient CLPs show no B lineage gene transcription and lack IgH chain recombination; Pax5, Pou2af1 (OcaB), and FoxO1 promoters contain functional EBF1 binding sites, establishing them as direct EBF1 target genes. Bone marrow transplantation of EBF1-deficient fetal liver cells, gene expression analysis, promoter binding site validation Journal of immunology High 18714008
2009 EBF reprograms mb-1 (Ig-alpha) promoters by increasing chromatin accessibility and initiating DNA demethylation, facilitating subsequent promoter activation by Pax5. SWI/SNF ATPases (Brg1/Brm) are required for transcriptional activation by EBF, while Mi-2/NuRD complex (Mi-2beta) opposes EBF by maintaining hypermethylated chromatin; knockdown of Mi-2beta greatly enhances chromatin accessibility and mb-1 transcription in response to EBF. Inducible EBF:ER and Pax5:ER fusion systems, shRNA knockdown of Brg1/Brm and Mi-2beta, chromatin accessibility assays, DNA methylation analysis Proceedings of the National Academy of Sciences of the United States of America High 19549820
2009 Ebf1-mediated downregulation of both Id2 and Id3 is essential for B cell lineage specification; enforced Ebf1 expression in IL-7Ralpha-/- bone marrow potently downregulates Id2 and Id3 mRNA and restores B cell differentiation in vivo; overexpression of either Id2 or Id3 in wild-type bone marrow blocks B cell specification at the prepro-B cell stage. Retroviral transduction of Ebf1 in IL-7Ralpha-/- bone marrow, in vivo rescue, Id2/Id3 overexpression Proceedings of the National Academy of Sciences of the United States of America High 19122139
2009 Ebf1 plays a role in regulating both the osteoblast and adipocyte lineages in vivo; Ebf1-/- mice show increased osteoblast numbers, bone formation parameters, and serum osteocalcin, as well as dramatically increased adipocyte numbers in bone marrow; Ebf1-deficient mice display features of lipodystrophy. Ebf1 knockout mouse analysis, histomorphometry, serum markers, histology Bone High 19130908
2010 The crystal structure of Ebf1 dimer bound to its palindromic recognition site reveals a pseudoimmunoglobulin-like fold with structural similarity to Rel homology domains of NFAT and NF-κB; each Ebf1 monomer contacts both palindromic half-sites via two loop-based modules and a unique Zn coordination motif, generating an extended contact area. X-ray crystallography Genes & development High 20876732
2010 Crystal structures of EBF family protein domains reveal: (1) DNA-binding domain resembling Rel homology superfamily but containing a unique zinc knuckle; (2) an IPT/TIG domain; (3) an atypical helix-loop-helix domain with a novel dimerization motif. X-ray crystallography of structured domains The Journal of biological chemistry High 20592035
2010 E2A and EBF1 bind regulatory elements in the Foxo1 locus; E2A and EBF1, as well as E2A and Foxo1, are wired together by cis-regulatory sequences; E47 occupancy directly results in H3K4 monomethylation across enhancer regions, establishing a positive regulatory network among E2A, EBF1, and Foxo1 in pro-B cells. ChIP-seq, genome-wide analysis of regulatory elements, histone modification analysis Nature immunology High 20543837
2010 EBF1 identifies the TET2 interaction partner; ChIP and western blotting show EBF1 interacts with TET2, suggesting a sequence-specific mechanism for TET2-mediated DNA demethylation. Chromatin immunoprecipitation, western blotting, sequence motif analysis Nature communications Low 23863747
2011 EBF1 is required for proliferation and survival of pro-B cells, and for signaling and function of peripheral B-cell subsets including B1 cells and marginal zone B cells; EBF1 targets c-Myb and Bcl-xL rescue survival defects; in mature B cells, EBF1 deficiency impairs BAFF-R and BCR-dependent Akt signaling; EBF1 is required for germinal center formation and class switch recombination. Conditional Ebf1 inactivation, v-Abl transformation, forced expression of EBF1 targets, genome-wide ChIP-seq and RNA analysis Genes & development High 22431510
2011 EBF1 and FOXO1 act in a positive intergenic feedback circuitry; depletion of EBF1 severely reduces FOXO1 mRNA abundance in LY6D+ CLPs, and depletion of FOXO1 ablates EBF1 transcript levels; their transcriptional signatures in deficient cells are strikingly similar, indicating a common set of target genes. EBF1 and FOXO1 knockout mouse analysis, genome-wide transcription factor occupancy (ChIP-seq), transcriptome analysis Proceedings of the National Academy of Sciences of the United States of America High 23213261
2011 Ebf1 represses Rag transcription in pro-B cells downstream of Stat5/IL-7R signaling; Ebf1 directly regulates c-Myb, which also represses Rag; Ebf1 and c-Myb antagonize Foxo1 binding to the Rag locus; Ebf1 directly represses Foxo1 expression and directly activates Gfi1b expression. shRNA knockdown, chromatin immunoprecipitation, gene expression analysis in Abelson-transformed B cells Journal of immunology Medium 24068669
2012 Conditional deletion of Ebf1 in committed pro-B cells causes their conversion into innate lymphoid cells and T cells; EBF1 directly binds and represses Id2 and TCF-1 genes; both EBF1 and Pax5 are required for B lineage commitment by repressing distinct and common determinants of alternative cell fates. Conditional Ebf1 deletion in committed pro-B cells, lineage tracing, ChIP, gene expression analysis Nature immunology High 23812095
2012 Runx1-Cbfβ complexes bind the Ebf1 proximal promoter and are required for its epigenetic activation (Runx1-binding motifs are essential for reporter expression; Runx1-deficient pro-B cells have excessive H3K27 trimethylation at the Ebf1 proximal promoter); retroviral Ebf1 (but not Pax5) transduction into Runx1-deficient progenitors restores B cell development, establishing Runx1-Cbfβ as an upstream activator of Ebf1. Conditional Runx1/Runx3/Cbfβ deletion, ChIP, reporter assay, retroviral rescue The Journal of experimental medicine High 22665574
2012 EBF1 is essential for B cell commitment, pro-B to pre-B cell transition, and for generation of marginal zone, B-1, follicular and germinal center B cells; BCR activation results in impaired intracellular signaling in EBF1-deficient follicular B cells; ectopic EBF1 expression efficiently induces B-1 cell development at the expense of conventional B cells. Conditional mutagenesis, BCR signaling assays, ChIP-seq, RNA-seq The Journal of experimental medicine High 22473956
2013 EBF1 in mature adipocytes directly regulates components of PI3K/AKT, MAPK, and STAT1 signaling pathways; EBF1 knockdown significantly reduces insulin-stimulated glucose uptake and lipogenesis; genome-wide EBF1 occupies ~35,000 sites in adipocytes, mostly at enhancers, with cell-type-specific patterns distinct from B cells. EBF1 knockdown, transcriptional profiling, ChIP-seq, glucose uptake and lipogenesis assays The Journal of biological chemistry High 24174531
2013 Zfp521 physically interacts with EBF1 and represses its transcriptional activity; deletion of Zfp521 leads to increased Ebf1 activity in osteoblasts and osteoclasts; the bone phenotype of Zfp521+/- mice is rescued in Zfp521+/-:Ebf1+/- mice, establishing a Zfp521-EBF1 rheostat for bone homeostasis. Co-immunoprecipitation, conditional deletion, genetic rescue (double heterozygotes), transcriptional assays The Journal of experimental medicine High 23569325
2015 EBF1 heterozygosity results in increased DNA damage in pro-B cells and reduced expression of DNA repair genes including Rad51; ChIP data indicate Rad51 is a direct EBF1 target; combined heterozygous mutations in Ebf1 and Pax5 dramatically increase pro-B cell leukemia frequency in mice. Gene expression analysis, ChIP, DNA damage assays (UV), mouse leukemia model Blood Medium 25838350
2016 The EBF1 C-terminal domain (CTD) is required for a specific set of B-lineage genes and promotes de novo chromatin accessibility and DNA demethylation in previously naive chromatin (pioneer function); the CTD enables EBF1 to bind inaccessible genomic regions with 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, comparison of EBF1wt and EBF1ΔC-expressing Ebf1-/- progenitor cells Immunity High 26982363
2016 CCR4-NOT complex interacts with EBF1; CNOT3 directly interacts with EBF1 at histidine 240 (H240A mutation disrupts this); the EBF1–CCR4-NOT interaction regulates gene-specific transcription and mRNA stability; mice with conditional Cnot3 inactivation phenocopy the block in early B cell differentiation, associated with impaired EBF1 autoregulation and reduced pre-BCR component expression. SILAC-based mass spectrometry of EBF1-associated proteins, mutagenesis (H240A), complementation of Ebf1-/- progenitors, conditional Cnot3 knockout, gene expression analysis Genes & development High 27807034
2016 MEF2C and EBF1 co-regulate a subset of B cell-specific genes at shared binding sites; MEF2C interacts with HDAC7 to repress myeloid transcription programs; the p38 MAPK pathway activates MEF2C to drive B cell differentiation. Genome-wide MEF2C and EBF1 ChIP-seq, Mef2c knockout mouse, co-immunoprecipitation PLoS genetics Medium 26900922
2017 EBF1 binds EBNA2 via EBNA2's N-terminal domain; EBF1 promotes assembly of EBNA2 chromatin complexes at CBF1-independent binding sites in B cells; EBNA2 exploits EBF1 to support metabolic processes and cell cycle progression (S-phase) in EBV-infected B cells, with the α1-helix of EBNA2's END domain promoting EBF1 binding. Co-immunoprecipitation, ChIP-seq, CBF1-deficient B cell analysis, EBV mutant analysis PLoS pathogens High 28968461
2018 EBF1 functions as a pioneer transcription factor: in a time-resolved analysis, EBF1 occupancy precedes formation of chromatin accessibility; EBF1 also transiently occupies lineage-inappropriate genes prior to their silencing in pro-B cells; continuous EBF1 function is required for Cd79a promoter activity and maintenance of an accessible chromatin domain. Inducible EBF1 expression system in Ebf1-/- pre-pro-B cells, time-resolved ATAC-seq, ChIP-seq, gene expression analysis Genes & development High 29440261
2019 EBF1 regulates glomerular development through its actions in Foxd1+ stromal/mesangial progenitor cells; EBF1 deficiency in Foxd1-lineage cells impairs calcineurin/NFATc1 activation and decreases COX-2 expression; overexpressing COX-2 in EBF1-deficient mice partially restores glomerular development. Conditional Ebf1 deletion (Foxd1-cre, Podocin-cre), COX-2 overexpression rescue, signaling pathway analysis Journal of the American Society of Nephrology Medium 31405952
2020 EBF1's C-terminal domain (CTD) harbors a prion-like domain (PLD) capable of liquid-liquid phase separation, which is enhanced by interaction with the RNA-binding protein FUS; the CTD stabilizes EBF1 chromatin occupancy via recruitment of the chromatin remodeler Brg1; Brg1 partitions into phase-separated FUS condensates and co-localizes with EBF1 and FUS foci in pro-B cells; heterologous PLDs can confer pioneering function on EBF1ΔCTD. Phase separation assays, co-immunoprecipitation of FUS and Brg1, live-cell imaging, FRAP, heterologous domain rescue Immunity High 33159853
2020 Conditional deletion of Ebf1 in bone marrow mesenchymal stromal cells (CAR cells/PαS cells) alters their cellular composition, chromatin structure, and gene expression (including reduced adhesion-related genes), impairs HSC adhesion leading to reduced HSC quiescence and diminished myeloid output, and causes persistent changes in HSC chromatin structure that persist through serial transplantations. Conditional Ebf1 deletion in MSCs, single-cell analysis, ATAC-seq, serial transplantation Nature immunology High 32066955
2021 EBF1 directly activates Myc expression through six EBF1-responsive enhancer elements within the Myc locus, with one element of key importance identified by CRISPR-Cas9 targeting of EBF1-binding sites; PAX5, in contrast, represses Myc expression; ectopic MYC partially rescues B-cell expansion in EBF1-deficient cells, establishing Myc as a direct EBF1 target in pro-B-cell expansion. Chromosome conformation analysis, ATAC-seq, ChIP-seq, reporter assays, CRISPR-Cas9 mutagenesis, in vivo and in vitro rescue Blood High 33619557
2021 EBF1 is expressed in pericytes and contributes to pericyte cell commitment; EBF1 silencing in human brain vascular pericytes reduces PDGFRβ, CD146, VEGF, angiopoietin-1, NG2, and TGF-β expression but not CD90, a mesenchymal marker. Immunohistochemistry, RT-qPCR, FACS, EBF1 siRNA knockdown in human pericytes Histochemistry and cell biology Medium 34272603
2022 EBF1 drives triple-negative breast cancer tumorigenicity by assembling a transcriptional complex with HIF1α that suppresses p300 activity, thereby fine-tuning HIF1α target gene expression and preventing excessive mitophagy-induced cell death; EBF1 depletion induces extensive cell mitophagy. EBF1 depletion, genome-wide ChIP-seq, co-immunoprecipitation, mitophagy assays Proceedings of the National Academy of Sciences of the United States of America Medium 35867755
2022 Derepression and nuclear repositioning of EBF1 from the heterochromatic nuclear envelope to the euchromatic nuclear interior in T-ALL cells instructs widespread genome refolding (alterations in compartments, domain boundaries, enhancer positioning) and promotes targeted therapy resistance. Hi-C, ATAC-seq, ChIP-seq, imaging of nuclear repositioning, integrated multi-omics in therapy-sensitive and -resistant T-ALL Molecular cell Medium 35182476
2024 Acute in vivo protein degradation reveals that Ebf1 functions predominantly as a transcriptional activator by inducing open chromatin at its target genes; Ebf1 represses Wapl (cohesin-release factor) to mediate prolonged loop extrusion across the Igh locus; Ebf1 directly activates surrogate light-chain genes Igll1 and Vpreb1 in pro-B cells; Ebf1 has largely unique target genes compared to E2A and Pax5 and is essential for early B cell maintenance. Acute protein degradation in mice (degron system), ATAC-seq, ChIP-seq, RNA-seq across pro-B, small pre-B, and immature B cells Nature immunology High 39179932

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 636 14675532
1995 Failure of B-cell differentiation in mice lacking the transcription factor EBF. Nature 539 7542362
2010 A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate. Nature immunology 413 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
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 183 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 168 23812095
2004 Cellular immune response to parasitization in Drosophila requires the EBF orthologue collier. PLoS biology 162 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 141 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
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 122 26748855
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
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) 114 18714008
2012 Essential role of EBF1 in the generation and function of distinct mature B cell types. The Journal of experimental medicine 108 22473956
2016 EBF1-PDGFRB fusion in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL): genetic profile and clinical implications. Blood 106 26872634
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 87 23213261
2014 Collier/OLF/EBF-dependent transcriptional dynamics control pharyngeal muscle specification from primed cardiopharyngeal progenitors. Developmental cell 81 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 72 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
2009 Silencing Sl-EBF1 and Sl-EBF2 expression causes constitutive ethylene response phenotype, accelerated plant senescence, and fruit ripening in tomato. Journal of experimental botany 69 19903730
2020 A Prion-like Domain in Transcription Factor EBF1 Promotes Phase Separation and Enables B Cell Programming of Progenitor Chromatin. Immunity 66 33159853
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
2011 IL-7 mediates Ebf-1-dependent lineage restriction in early lymphoid progenitors. Blood 65 21652681
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
2003 EBF-regulating Pax5 transcription is enhanced by STAT5 in the early stage of B cells. European journal of immunology 61 12811842
1998 Molecular cloning of Zcoe2, the zebrafish homolog of Xenopus Xcoe2 and mouse EBF-2, and its expression during primary neurogenesis. Mechanisms of development 61 9784615
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
2016 EBNA2 Drives Formation of New Chromosome Binding Sites and Target Genes for B-Cell Master Regulatory Transcription Factors RBP-jκ and EBF1. PLoS pathogens 56 26752713
2002 Oscillation between B-lymphoid and myeloid lineages in Myc-induced hematopoietic tumors following spontaneous silencing/reactivation of the EBF/Pax5 pathway. Blood 53 12406913
2012 Lentiviral vector induced insertional haploinsufficiency of Ebf1 causes murine leukemia. Molecular therapy : the journal of the American Society of Gene Therapy 52 22472950
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 47 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
2017 Aryl Hydrocarbon Receptor Activation Suppresses EBF1 and PAX5 and Impairs Human B Lymphopoiesis. Journal of immunology (Baltimore, Md. : 1950) 42 28978690
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
2015 Combined heterozygous loss of Ebf1 and Pax5 allows for T-lineage conversion of B cell progenitors. The Journal of experimental medicine 38 26056231
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
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
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
2020 TMPO-AS1/miR-98-5p/EBF1 feedback loop contributes to the progression of bladder cancer. The international journal of biochemistry & cell biology 30 32087328
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
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
2022 EBF1 nuclear repositioning instructs chromatin refolding to promote therapy resistance in T leukemic cells. Molecular cell 28 35182476
2017 EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes in B cells. PLoS pathogens 28 28968461
2016 Rewiring of an ancestral Tbx1/10-Ebf-Mrf network for pharyngeal muscle specification in distinct embryonic lineages. Development (Cambridge, England) 28 27802138
2005 Evi3, a zinc-finger protein related to EBFAZ, regulates EBF activity in B-cell leukemia. Oncogene 28 15580294
2023 Brassinosteroids promote etiolated apical structures in darkness by amplifying the ethylene response via the EBF-EIN3/PIF3 circuit. The Plant cell 27 36321994
2021 EBF1 is expressed in pericytes and contributes to pericyte cell commitment. Histochemistry and cell biology 27 34272603
2016 Interaction of CCR4-NOT with EBF1 regulates gene-specific transcription and mRNA stability in B lymphopoiesis. Genes & development 27 27807034
2015 ZNF423 and ZNF521: EBF1 Antagonists of Potential Relevance in B-Lymphoid Malignancies. BioMed research international 25 26788497
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
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 24 35867755
2020 EBF1 and Pax5 safeguard leukemic transformation by limiting IL-7 signaling, Myc expression, and folate metabolism. Genes & development 24 33004416
2019 An ancient role for collier/Olf/Ebf (COE)-type transcription factors in axial motor neuron development. Neural development 24 30658714
2017 Deregulation of kinase signaling and lymphoid development in EBF1-PDGFRB ALL leukemogenesis. Leukemia 24 28555080
2013 Ebf1 and c-Myb repress rag transcription downstream of Stat5 during early B cell development. Journal of immunology (Baltimore, Md. : 1950) 23 24068669
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
2019 Early B Cell Factor 1 (EBF1) Regulates Glomerular Development by Controlling Mesangial Maturation and Consequently COX-2 Expression. Journal of the American Society of Nephrology : JASN 22 31405952
2017 MicroRNAs-361-5p and miR-574-5p associate with human adipose morphology and regulate EBF1 expression in white adipose tissue. Molecular and cellular endocrinology 22 29191698
2024 Transcriptional function of E2A, Ebf1, Pax5, Ikaros and Aiolos analyzed by in vivo acute protein degradation in early B cell development. Nature immunology 21 39179932

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