| 2013 |
EBF2 recruits PPARγ to brown adipose-specific binding sites to determine brown versus white adipocyte identity; the EBF DNA-binding motif is highly enriched within brown adipose-specific PPARγ binding sites identified by ChIP-seq, and expression of EBF2 in myoblasts or white preadipose cells reprograms cells to a brown fat fate. |
ChIP-seq, ectopic expression in myoblasts/white preadipose cells, Ebf2 knockout mice |
Cell metabolism |
High |
23499423
|
| 2017 |
EBF2 physically interacts with the BAF chromatin remodeling complex (via BRG1) and recruits it to lineage-specific enhancers in brown adipocytes; EBF2 directly transcriptionally activates DPF3, a brown fat-selective BAF subunit, which in turn is required for chromatin accessibility at EBF2-bound enhancers and for brown fat gene programming. |
ChIP-seq, co-immunoprecipitation (EBF2–BRG1 interaction), DPF3 loss-of-function (ATAC-seq/chromatin accessibility), direct promoter activation assays |
Genes & development |
High |
28428261
|
| 2021 |
ZFP423 physically interacts with EBF2 and recruits the NuRD corepressor complex to EBF2-bound thermogenic gene enhancers in white adipocytes; disruption of the ZFP423–EBF2 protein–protein interaction via CRISPR-Cas9 editing triggers an EBF2 NuRD-to-BAF coregulator switch, shifts PPARγ occupancy toward thermogenic genes, and induces widespread browning of WAT. |
Co-IP, CRISPR-Cas9 disruption of protein–protein interaction, ChIP-seq (PPARγ occupancy), Zfp423 conditional KO |
Genes & development |
High |
34620682
|
| 2005 |
EBF2 binds to sequences in the Opg (osteoprotegerin) promoter and transactivates it in synergy with the Wnt-responsive LEF1/TCF:β-catenin pathway; loss of Ebf2 in mice causes downregulation of OPG, leading to increased osteoclast numbers and reduced bone mass. |
Promoter binding/transactivation assays, Ebf2 targeted knockout mice, osteoclast phenotype analysis |
Developmental cell |
High |
16326388
|
| 2006 |
EBF1 and EBF2 promote adipogenesis by directly activating the PPARγ1 and C/EBPα promoters; EBF1 is itself induced by C/EBPβ/δ; knockdown of Ebf1/Ebf2 by shRNA blocks 3T3-L1 differentiation, placing EBF proteins within the core adipogenic transcriptional cascade. |
Promoter activation assays (direct binding), shRNA knockdown in 3T3-L1 cells, ectopic expression in NIH 3T3 fibroblasts |
Molecular and cellular biology |
Medium |
17060461
|
| 2003 |
Loss of Ebf2 in mice causes defective migration of GnRH-synthesizing neurons, impaired formation of the neuroendocrine axis, and hypogonadotropic hypogonadism; Ebf2-null peripheral nerves show axon-sorting defects, hypomyelination, and severely reduced motor nerve conduction velocity, establishing EBF2 as required for GnRH neuron migration and peripheral nerve development. |
Targeted Ebf2 gene deletion in mice, histological/neuroanatomical analysis, electrophysiology (motor nerve conduction velocity) |
Development (Cambridge, England) |
High |
12466206
|
| 2014 |
Ebf2 marks and regulates embryonic brown adipogenic precursor cells; Ebf2-expressing cells from brown fat tissue uniformly differentiate into brown adipocytes, those from white fat into beige adipocytes; loss of Ebf2 reduces brown preadipose-signature genes while ectopic Ebf2 expression in myoblasts activates brown preadipose-specific genes. |
Ebf2-GFP reporter mouse, prospective cell isolation, RNA-seq, loss-of-function (Ebf2 KO), ectopic expression in myoblasts |
Proceedings of the National Academy of Sciences of the United States of America |
High |
25197048
|
| 2015 |
EBF2 is required for beige adipocyte development; Ebf2 knockout mice fail to induce UCP1 or a thermogenic program in subcutaneous WAT following adrenergic stimulation, and EBF2 overexpression in adipocyte cultures or transgenic adipose tissue is sufficient to induce UCP1 expression, brown-like differentiation, and increased mitochondrial function. |
Ebf2 KO mice, transgenic Ebf2 overexpression in adipose tissue, primary adipose cell cultures, adrenergic stimulation, UCP1 and mitochondrial function assays |
Molecular metabolism |
High |
26844207
|
| 2009 |
EBF2 functions as a transcriptional activator of OPG in osteosarcoma; knockdown of EBF2 reduces OPG levels and increases sensitivity to TRAIL-induced apoptosis, demonstrating that EBF2-driven OPG expression contributes to TRAIL resistance in osteosarcoma. |
Lentiviral shRNA knockdown of EBF2, real-time PCR, ELISA (OPG protein), caspase-3/7 apoptosis assay |
Clinical cancer research |
Medium |
19671856
|
| 2011 |
Ebf2 is expressed in Schwann cells; loss of Ebf2 delays the onset of myelination, downregulates Schwann cell differentiation markers, causes nodal region abnormalities, shorter internodal length, and impairs motor nerve conduction velocity and amplitude, establishing EBF2 as required for peripheral nerve myelination and Schwann cell differentiation. |
Ebf2 KO mice, immunohistochemistry, electrophysiology (nerve conduction), morphometric analysis |
Neurobiology of disease |
High |
21220016
|
| 2016 |
EBF1 and EBF2 act as positive regulators of myelination in Schwann cells; combined knockdown of Ebf genes in myelinating dorsal root ganglia cultures severely impairs myelin formation, rescued by specific overexpression; EBF target gene profiling identifies Gliomedin as a direct target regulated by EBF factors in peripheral myelination. |
siRNA/shRNA knockdown and overexpression in DRG myelinating cultures, EBF target gene profiling, promoter regulation assays for Gliomedin |
Molecular neurobiology |
Medium |
27889898
|
| 2012 |
Loss of Ebf2 causes a transient decrease in Cajal-Retzius cell numbers on the cortical surface due to a migratory defect originating from the cortical hem; both EBF2 and EBF3 directly control CR cell migration in vitro. |
Ebf2 KO mice, fate-mapping studies, in vitro cortical hem preparations with migration assays |
Developmental biology |
Medium |
22421355
|
| 2011 |
Ebf2 overexpression increases the generation of early-born neurons including Cajal-Retzius cells, while Ebf2 knockdown decreases it, demonstrating a direct regulatory role for EBF2 in cortical neurogenesis and CR neuron generation without affecting other layer-specific neurons. |
Lentiviral-mediated knockdown and overexpression in cortical cultures, Ebf2-EGFP transgenic reporter line |
Developmental neuroscience |
Medium |
22042145
|
| 2015 |
Loss of Ebf2 in vivo causes a marked reduction in dopaminergic neuron number specifically in the midbrain periaqueductal gray matter but not in the substantia nigra or ventral tegmental area, demonstrating a selective requirement for EBF2 in PAG DA neuron development. |
Ebf2 KO mice, immunohistochemistry, quantification of TH+ neurons across midbrain subregions |
Developmental neurobiology |
Medium |
25762221
|
| 2023 |
EBF2 binds H3K4me1 (monomethylated histone H3 Lys4) and cooperates with KMT2D (which catalyzes H3K4me1) at the KLLN gene promoter region to activate KLLN transcription; KMT2D and EBF2 cooperatively suppress PDAC cell proliferation, migration, and invasion through KLLN upregulation. |
ChIP-seq, RNA-seq, co-occupancy analysis, functional assays (proliferation, migration, invasion), EBF2 identified as H3K4me1-binding protein |
Advanced science |
Medium |
38015024
|
| 2024 |
SOX4 activates EBF2 transcription by directly binding its promoter; SOX4 and EBF2 cooperate to activate thermogenic gene expression in brown adipose tissue; phosphorylation of SOX4 at Ser235 by PKA promotes its nuclear translocation and thereby enhances EBF2 transcription. |
Sox4 conditional KO mice, SOX4 overexpression in BAT, ChIP assays (SOX4 binding to EBF2 promoter), co-immunoprecipitation (SOX4–EBF2 complex), PKA phosphorylation assays |
Cell death and differentiation |
Medium |
39402212
|
| 2025 |
The deubiquitinating enzyme USP2 physically interacts with EBF2 and stabilizes it by removing ubiquitin, thereby preventing EBF2 degradation; BAT-specific Usp2 knockdown impairs thermogenic programs, while Usp2 overexpression in BAT protects against obesity; EBF2 was identified as the substrate of USP2 mediating its thermogenic function. |
Co-immunoprecipitation, quantitative proteomics (substrate identification), adeno-associated virus and lentivirus KD/OE in vivo and in vitro, metabolic phenotyping |
Molecular metabolism |
Medium |
40189098
|
| 2025 |
EBF2 directly regulates mitochondrial membrane phospholipid composition in brown adipocytes; Myf5Cre-driven Ebf2 deletion drastically reduces cardiolipin and phosphatidylethanolamine abundance and alters acyl chain remodeling; EBF2 directly binds the Srebf1 promoter and regulates expression of cardiolipin/PE-synthesizing genes; Ebf2 deletion reduces DRP1 and OPA1 levels, impairing mitochondrial fission-fusion dynamics. |
Myf5Cre conditional Ebf2 KO mice, lipidomics, ChIP (EBF2 binding to Srebf1), gene expression analysis, electron microscopy |
Journal of lipid research |
Medium |
40865612
|
| 2026 |
Cars2-generated cysteine persulfide post-translationally modifies EBF2 via persulfidation; persulfidated EBF2 shows enhanced interaction with PPARγ and BRG1, increasing recruitment of the EBF2–PPARγ complex to browning gene promoters to drive brown fat development and thermogenesis; Cars2 is itself a direct transcriptional target of EBF2. |
Co-IP (EBF2–PPARγ and EBF2–BRG1 interactions after persulfidation), ChIP (EBF2-PPARγ complex at browning gene promoters), Cars2 KO in thermogenic fat, H2S donor treatment, EBF2 persulfidation biochemical assays |
Advanced science |
Medium |
41849685
|
| 2026 |
EBF2 contains a low-complexity C-terminal domain (CTD) that drives biomolecular condensate (phase separation) formation; deletion of the CTD or mutation of conserved proline residues disrupts EBF2 phase separation without affecting genomic occupancy; EBF2 condensates sequester the transcriptional repressor ZFP423 and exclude HDAC1, creating a permissive chromatin environment for thermogenic gene expression; fusion of an IDR from FUS but not MED1 rescues condensate function. |
EBF2 ΔCTD/proline mutants in vitro and in male mice, live-cell condensate imaging, co-immunoprecipitation (ZFP423/HDAC1 in condensates), ChIP, small-molecule condensate screen |
Nature communications |
Medium |
42026085
|
| 2026 |
A heterozygous nonsense EBF2 variant (p.E165X) impairs adipocyte differentiation and adipose tissue remodeling in vitro and in Ebf2E165X/+ knock-in mice; the variant causes excess accumulation of undifferentiated CD34+ cells, defective extracellular matrix remodeling, abnormal adipocyte hypertrophy, reduced adiponectin/leptin expression, glucose intolerance, and downregulation of mitochondrial fatty acid metabolism genes specifically in adipose tissue. |
Heterozygous knock-in (Ebf2E165X/+) mice, in vitro adipogenesis assays, gene expression analysis, metabolic phenotyping, histology |
The Journal of clinical investigation |
High |
41615236
|
| 2024 |
EBF2 interacts with transcriptional co-activators CBP/P300 to induce H3K27ac deposition and chromatin activation at brown adipose tissue-associated genes, driving progressive specification of the brown fat lineage from Pax7+ mesodermal stem cells; EBF2 expression during a critical embryonic window (E10.5–E14.5 in mouse) is required for BAT lineage specification. |
ChIP-seq (H3K4me3, H3K27me3, H3K27ac dynamics), Co-IP (EBF2–CBP/P300 interaction), comparative mouse/pig analysis, ectopic EBF2 expression in mesodermal stem cells |
Journal of advanced research |
Medium |
39736442
|
| 2025 |
SOX4 forms two independent complexes with EBF2 and with PPARγ to promote thermogenic gene expression in BAT; SOX4 directly binds the promoter regions of thermogenic genes independent of EBF2; deletion of SOX4 in BAT (Sox4-BKO mice) downregulates thermogenic and oxidative phosphorylation genes and reduces mitochondrial numbers. |
Co-immunoprecipitation (SOX4–EBF2 and SOX4–PPARγ complexes), ChIP (SOX4 direct binding to thermogenic gene promoters), Sox4 conditional KO (Ucp1Cre+), in vitro loss-of-function |
Advanced biology |
Medium |
40977422
|
| 2018 |
miR-204-5p directly binds the 3' UTR of EBF2 mRNA to regulate its stability; overexpression of EBF2 inhibits apoptosis and promotes migration and invasion of osteosarcoma cells, and EBF2 overexpression rescues the pro-apoptotic/anti-migratory phenotype caused by miR-204-5p overexpression. |
Luciferase reporter assay (miR-204-5p binding to EBF2 3'UTR), EBF2 overexpression rescue experiments, apoptosis assays, migration/invasion assays, xenograft model |
Biochimie |
Medium |
30529043
|