Affinage

EGR1

Early growth response protein 1 · UniProt P18146

Length
543 aa
Mass
57.5 kDa
Annotated
2026-06-09
100 papers in source corpus 44 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EGR1 is an immediate-early zinc-finger transcription factor that converts extracellular growth factor, stress, and hormonal cues into nuclear gene programs by binding GC-rich promoter and enhancer elements (consensus GCGGGGGCG) through its zinc fingers (PMID:7891721). Its protein contains four distinct activation domains and a discrete inhibitory (R1) domain whose deletion sharply increases activity by relieving a titratable cellular repressor (PMID:8413279); this domain is the docking site for the corepressors NAB1 and NAB2, which repress EGR1- and Krox20-directed transcription without blocking DNA binding or nuclear import, NAB1 acting through an active repression domain (NCD2) in its carboxy terminus (PMID:7624335, PMID:9418898, PMID:8668170). EGR1 expression and protein output are driven principally through EGFR–MEK–ERK signaling (PMID:19414352, PMID:31725811), with GR/glucocorticoid–MAPK input in the hippocampus (PMID:15834420) and additional control by the mTORC1/4E-BP translational axis (PMID:25814662); its stability and activity are further tuned post-translationally, with Akt phosphorylation at S350/T309 promoting ARF/Ubc9-dependent sumoylation required for PTEN induction (PMID:19057511), DNA-PKcs phosphorylation at S301 protecting EGR1 from proteasomal degradation to sustain IL-2 transcription (PMID:34562454), and sumoylation-coupled ubiquitination promoting turnover (PMID:21998680). As a transcriptional node EGR1 activates or represses context-specific targets—activating Col1a1/Col2a1 in tendon differentiation (PMID:21173153, PMID:23863709), TAp73 and p53 in stress apoptosis (PMID:16990849, PMID:30887692), Per1 within the circadian feedback loop (PMID:26471974), TFEB (PMID:36888606), CCND1 (PMID:29246166), and SNAI2 in cancer (PMID:36932397), while repressing PFKL to limit glycolysis (PMID:38287371) and inflammatory enhancer genes via the NuRD complex (PMID:33523892). It cooperates with coactivators p300/CBP (PMID:36932397, PMID:33980611), recruits TET1 for neuronal DNA demethylation (PMID:31467272), and partners with SMAD3, TBX2, RUNX2, and TET2 to set target-gene output in a context-dependent manner (PMID:20149866, PMID:29719592, PMID:32324256, PMID:35115654). Genetic loss of Egr1 in mice causes sterility, failed LHβ synthesis in gonadotropes, and somatotrope deficits (PMID:9440815), underscoring its requirement across reproductive, tendon, cardiac, circadian, and metabolic processes.

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1989 Medium

    Establishing the EGR1 gene's structure and inducibility defined it as an NGF/serum-responsive immediate-early gene with its DNA-contacting zinc fingers encoded in a single 3' exon.

    Evidence Gene cloning/sequencing and CAT reporter transfection of the 5' flanking region in PC12 cells

    PMID:2492104

    Open questions at the time
    • Did not define the DNA target sequence recognized by the protein
    • Promoter dissection in a single cell type
  2. 1993 High

    Dissecting the EGR1 protein into functional domains showed it carries multiple activation domains plus an inhibitory domain that binds a titratable cellular factor, explaining why its intrinsic activity is held in check.

    Evidence GAL4-fusion cotransfection, deletion/point mutagenesis (I293F), and competition assays in mammalian and Drosophila cells

    PMID:8413279

    Open questions at the time
    • Identity of the titratable inhibitory factor not established in this study
    • No DNA-binding or in vivo target validation
  3. 1995 High

    Identifying the consensus GC-rich binding site and the NAB1 corepressor explained how EGR1 selects targets and how its activity is silenced without affecting DNA binding or localization.

    Evidence PCR-based random site selection with EMSA/affinity measurements, and yeast two-hybrid plus cotransfection repression assays

    PMID:7624335 PMID:7891721 PMID:9418898

    Open questions at the time
    • Mechanism by which NAB1 represses once bound not yet defined
    • Family selectivity (no repression of Egr3/NGFI-C) mechanism unclear
  4. 1996 High

    NAB2, a co-induced paralog of NAB1, was shown to bind the same R1 domain and repress EGR1, establishing a feedback corepressor module coupled to EGR1 induction.

    Evidence Domain interaction mapping, cotransfection repression, and Northern blot expression analysis

    PMID:8668170

    Open questions at the time
    • Repression mechanism downstream of binding not defined here
    • Physiological context of NAB2 feedback not tested in vivo
  5. 1998 High

    Genetic ablation and mapping of an active NAB1 repression domain (NCD2) resolved how EGR1 silencing works and demonstrated EGR1's developmental necessity for endocrine cell lineages.

    Evidence GAL4-tethered repression/mutagenesis assays and Egr1 null mouse histopathology/hormone analysis

    PMID:9418898 PMID:9440815

    Open questions at the time
    • Corepressor machinery recruited by NCD2 not identified
    • Cell-autonomy of somatotrope/gonadotrope defects not fully resolved
  6. 2006 High

    Defining EGR1 activation of TAp73 (and later p53) placed EGR1 within a stress-responsive apoptotic transcriptional network with feedback amplification.

    Evidence Promoter reporter assays, binding-site mutagenesis, ChIP, and in vivo mouse genotoxic stress experiments

    PMID:16990849

    Open questions at the time
    • Stress-specific signaling that activates EGR1 in this network not defined
    • Cofactor requirements for TAp73 induction unspecified
  7. 2008 High

    Mapping Akt-driven phosphorylation/ARF-dependent sumoylation versus sumoylation-coupled ubiquitination revealed that PTMs both license target induction (PTEN) and control EGR1 turnover.

    Evidence In vivo phosphorylation/sumoylation assays, co-IP, site-directed mutagenesis, ARF-/- mice (PTEN axis), and SUMO-1/Ubc9 cotransfection with MG132 ubiquitination assays

    PMID:19057511 PMID:21998680

    Open questions at the time
    • How sumoylation can both activate and destabilize EGR1 reconciled only partially
    • Physiological stimuli balancing these PTMs unclear
  8. 2009 Medium

    Pharmacological pathway dissection established that EGFR signaling induces EGR1 specifically through MEK/ERK rather than PI3K, defining the dominant upstream route.

    Evidence Expression profiling with MEK (U0126) versus PI3K (LY294002) inhibitors in mutant-EGFR cells

    PMID:19414352

    Open questions at the time
    • Single cell-line pharmacology
    • Transcription factors mediating ERK-to-EGR1 induction not identified
  9. 2013 High

    In vivo ChIP and rescue experiments established EGR1 as a direct activator of collagen genes driving tendon differentiation and repair via TGF-β2.

    Evidence In vivo ChIP at Col1a1/Col2a1, Egr1-/- tendon analysis, MSC overexpression, and a rat Achilles tendon injury model with TGF-β2 neutralization

    PMID:21173153 PMID:23863709

    Open questions at the time
    • Cofactors enabling tenogenic versus other programs not defined
    • Extent of TGF-β2-independent contribution unresolved
  10. 2008 High

    Genome-wide promoter mapping after UV/EGFR activation showed EGR1 binds hundreds of promoters, including EGFR-pathway and pro-apoptotic genes, defining it as a broad signal-responsive regulatory hub.

    Evidence ChIP-on-chip with ChIP-qPCR validation, siRNA knockdown, and UV-induced apoptosis assays

    PMID:19032775

    Open questions at the time
    • Functional contribution of most bound promoters untested
    • Determinants of activation versus repression at each site unclear
  11. 2019 High

    Discovery that EGR1 recruits TET1 for neuron-specific demethylation and activates TFEB defined EGR1 as a writer of chromatin/epigenetic state coupling to lysosomal/metabolic programs.

    Evidence EGR1 ChIP-seq, WGBS, parallel Egr1-/-/Tet1-/- cortex comparison; and EGR1 ChIP-seq with KO and Trametinib in TFEB study

    PMID:31467272 PMID:36888606

    Open questions at the time
    • Direct EGR1–TET1 contact interface not mapped
    • Selectivity for neuronal versus glial recruitment mechanistically unexplained
  12. 2021 High

    Genome-wide profiling in myeloid cells demonstrated EGR1 represses inflammatory enhancers through the NuRD corepressor complex, defining a direct repressive mechanism complementary to its activator role.

    Evidence EGR1 ChIP-seq, ATAC-seq, NuRD co-IP, and EGR1 knockdown with inflammatory gene readout; plus DNA-PKcs-stabilized EGR1 sustaining IL-2

    PMID:33523892 PMID:34562454

    Open questions at the time
    • How EGR1 binds non-canonical (motif-less) enhancers unclear
    • Switch between NAB/NuRD repression and p300 activation not defined
  13. 2024 High

    Conditional-KO and multi-omics studies extended EGR1 to cardiac regeneration, hepatoprotective β-oxidation, and tumor-suppressive glycolytic control, broadening its physiological reach.

    Evidence Conditional Egr1 KO with proteomics/scRNA-seq (cardiac agrin model), liver-specific KO with ChIP-seq/Seahorse (Acaa2), and ChIP with organoid/xenograft models (PFKL)

    PMID:35813467 PMID:38287371 PMID:39196027

    Open questions at the time
    • Tissue-specific cofactors directing opposite (activating vs repressing) outputs not resolved
    • Whether shared upstream ERK/Akt input distinguishes these programs unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what molecular logic dictates whether EGR1 acts as an activator (with p300/CBP, TET1) or a repressor (with NAB1/2, NuRD, TET2/HDAC) at a given locus.
  • No structural or rule-based model linking partner choice to gene-specific outcome
  • Crosstalk between phosphorylation/sumoylation PTM state and cofactor recruitment not integrated
  • Determinants of binding at non-canonical enhancers undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 2 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-4839726 Chromatin organization 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9909396 Circadian clock 1
Partners
EP300NAB1NAB2RUNX2SMAD3TBX2TET1TET2
Complex memberships
NuRD complex

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 NGFI-A (EGR1) contains four transcriptional activation domains (acidic, proline/glutamine-rich, Krox-20 homology, and a novel domain) and an inhibitory domain whose removal causes a 15-fold increase in activity; competition and point-mutation experiments demonstrated the inhibitory domain interacts with a titratable cellular factor, and the I293F mutation in this domain abolishes the inhibitory interaction. GAL4-fusion cotransfection assay, deletion/point mutagenesis, competition experiments in mammalian and Drosophila cells Molecular and cellular biology High 8413279
1995 NAB1 is a nuclear corepressor that physically interacts with the inhibitory (R1) domain of NGFI-A (EGR1) and represses NGFI-A- and Krox20-mediated transcription, but does not repress Egr3 or NGFI-C, providing a mechanism for differential regulation of EGR family members. NAB1 does not block DNA binding or nuclear localization of NGFI-A. Yeast two-hybrid isolation, cotransfection repression assays, domain mapping Proceedings of the National Academy of Sciences of the United States of America High 7624335 9418898
1996 NAB2, a second corepressor highly related to NAB1, physically interacts with the R1 domain of NGFI-A (EGR1) through its first conserved domain and represses both NGFI-A and Krox20 transcriptional activity; NAB2 expression is induced by the same stimuli (serum, NGF) that induce NGFI-A. Domain interaction mapping, cotransfection repression assays, Northern blot expression analysis Molecular and cellular biology High 8668170
1998 Nab1 repression of EGR1 is not mediated by blocking DNA binding or nuclear localization; instead, Nab1 contains an active repression domain localized to the conserved NCD2 region in its carboxy terminus, and this domain can repress multiple types of activation domains when tethered directly to DNA, independent of promoter context or distance. GAL4-tethered repression assays, deletion/replacement mutagenesis, nuclear localization experiments, gel shift assays Molecular and cellular biology High 9418898
1995 EGR1 (NGFI-A) and related family members (NGFI-C, Egr3, Krox20) bind the consensus GC-rich sequence GCGGGGGCG; PCR-mediated random site selection revealed a broader consensus T-G-C-G-T/g-G/A-G-G-C/a/t-G-G/T and an optimal 10-nucleotide binding site. NGFI-C has >3-fold lower DNA binding affinity than NGFI-A/Egr3/Krox20 due to protein context outside the zinc fingers. PCR-based random site selection, gel shift assays, kinetic binding measurements Molecular and cellular biology High 7891721
1989 The rat NGFI-A (EGR1) gene spans 3789 nt with a single intron; all three zinc-finger domains are encoded in the 3' exon. The 5' flanking region contains an NGF-responsive element (with serum response elements, CRE, Sp1 site, TATA box) demonstrated by CAT reporter transfection in PC12 cells. Gene cloning/sequencing, CAT reporter transfection assay, transcription start site mapping Proceedings of the National Academy of Sciences of the United States of America Medium 2492104
2008 EGR1 is sumoylated in ECV304 cells upon EGF stimulation; SUMO-1/Ubc9 overexpression stabilizes ERK1/2 phosphorylation and increases EGR1 gene transcription, but simultaneously enhances EGR1 protein ubiquitination and proteasomal degradation, indicating that sumoylation promotes EGR1 turnover. Cotransfection of SUMO-1/Ubc9 constructs, immunoblotting, proteasome inhibitor (MG132) experiments, ubiquitination assays PloS one Medium 21998680
2008 EGR1 is phosphorylated by Akt at S350 and T309; this promotes interaction of EGR1 with ARF at K272 in its repressor domain, enabling ARF/Ubc9/SUMO-mediated sumoylation of EGR1, which is required for EGR1-dependent transcriptional induction of PTEN in vivo. ARF knockout mice show reduced EGR1 sumoylation and reduced PTEN. In vivo phosphorylation/sumoylation assays, co-immunoprecipitation, ARF-/- mouse analysis, site-directed mutagenesis The EMBO journal High 19057511
2021 DNA-PKcs phosphorylates EGR1 at serine 301 in activated T cells; inhibition of DNA-PKcs or S301A CRISPR mutation increases proteasomal degradation of EGR1 and decreases EGR1-dependent IL-2 transcription, identifying DNA-PKcs as a kinase that stabilizes EGR1. Quantitative phosphoproteomics, DNA-PKcs inhibitor (NU7441), shRNA knockdown, CRISPR-Cas9 S301A mutation, proteasome inhibitor assays, luciferase/transcription assays The Journal of biological chemistry High 34562454
2019 EGR1 recruits the DNA demethylase TET1 to EGR1 binding sites during postnatal brain development, establishing hypomethylation specifically in neurons (not glia); Egr1-/- and Tet1-/- frontal cortices share strikingly similar gene expression and DNA methylation profiles. EGR1 ChIP-seq, WGBS methylation profiling, knockout mouse comparison (Egr1-/-, Tet1-/-), co-immunoprecipitation/recruitment assays Nature communications High 31467272
2010 EGR1 (and EGR2) directly bind and trans-activate the proximal promoter of Col1a1 in tendon cells; FGF4 (muscle-derived) activates Egr1 expression and downstream collagen expression in chick limbs; Egr1-/- mice show reduced Col1a1 transcripts and fewer collagen fibrils in embryonic tendons. ChIP assay (EGR1 recruitment to Col1a1 promoter), luciferase reporter trans-activation, chick misexpression, Egr1-/- mouse analysis The Journal of biological chemistry High 21173153
2013 EGR1 is recruited to Col1a1 and Col2a1 promoters in postnatal mouse tendons in vivo; EGR1-expressing MSCs promote tendon-like tissue formation and Achilles tendon repair; EGR1's pro-tenogenic effect is partially mediated by TGF-β2. ChIP assay (in vivo promoter recruitment), Egr1-/- mouse tendon analysis, MSC overexpression, rat Achilles tendon injury model, TGF-β2 neutralization The Journal of clinical investigation High 23863709
2006 EGR1 transcriptionally activates the TAp73 promoter (TP73 P1) through five distinct EGR1-binding sites; EGR1 induction of TAp73 by genotoxic stress was confirmed in vivo in mice; EGR1, p53, and TAp73 form an inter-regulating network with feedback loops sustaining apoptotic gene expression under stress. Promoter reporter assays, EGR1-binding site mutagenesis, ChIP, in vivo mouse genotoxic stress experiments Cell death and differentiation High 16990849
2005 EGR1 binds to the heparanase (HPSE) gene promoter in vivo in tumor cells; two functional EGR1 binding sites in a 280-bp critical promoter region were identified by site-directed mutagenesis and EMSA; EGR1 activates heparanase promoter in prostate, breast, and colon carcinoma but represses it in melanoma cells. ChIP (in vivo promoter binding), luciferase reporter assays, site-directed mutagenesis, EMSA, EGR1 overexpression The Journal of biological chemistry High 16093249
2005 Glucocorticoid receptor activation in hippocampus increases MAPK (ERK) pathway activity and leads to increased Egr-1 mRNA and protein; MAPK pathway inhibition within hippocampus abolishes glucocorticoid-induced enhancement of contextual fear conditioning, placing EGR1 downstream of GR/MAPK signaling in stress-related fear memory. Brain-specific GR knockout mice (GR(NesCre)), cell lines with constitutively active GR (DeltaGR), MAPK inhibitor intra-hippocampal injection, fear conditioning behavioral assay Nature neuroscience High 15834420
2012 NGFI-A (EGR1) binds to the exon 1(7) glucocorticoid receptor (GR) promoter in hippocampus in a manner dynamically regulated by maternal licking/grooming; serotonin (5-HT) induces NGFI-A-dependent GR transcription in hippocampal neurons; thyroid hormones and 5-HT mediate LG-induced NGFI-A binding to the GR promoter. ChIP (NGFI-A binding to GR promoter), hippocampal neuron reporter assay, NGFI-A overexpression, thyroid hormone/5-HT pharmacological manipulations Philosophical transactions of the Royal Society of London. Series B, Biological sciences Medium 22826348
2014 MBD2 (methyl-CpG binding domain protein-2) collaborates with NGFI-A (EGR1) to activate the methylated exon 17 GR promoter; MBD2 knockdown abolishes exon 17 GR promoter activation; site-directed mutagenesis of the NGFI-A response element within the methylated promoter confirmed that NGFI-A binding is required. MBD2 knockdown in hippocampal primary culture, ectopic co-expression in HEK293 cells, site-directed mutagenesis of NGFI-A response element, luciferase reporter assay Philosophical transactions of the Royal Society of London. Series B, Biological sciences Medium 25135974
2008 UV irradiation activates EGF receptor, induces EGR1, and EGR1 then binds to 288 gene promoters (ChIP-on-chip); a major subgroup of bound targets is the EGFR signal-transduction pathway (24 genes); EGR1 binding impacts target gene expression, and siRNA depletion of EGR1 abolishes UV-induced apoptosis in prostate M12 cells, identifying FasL, MAX, and RRAS2 as novel EGR1 targets. ChIP-on-chip (genome-wide promoter binding), conventional ChIP-qPCR validation, siRNA knockdown, UV-induced apoptosis assay Genome biology High 19032775
2010 SMAD3 and EGR1 physically interact via the SMAD3 MH2 domain and the EGR1 DNA-binding domain; SMAD3 inhibits EGR1-induced human LHB promoter activity but potentiates EGR1-induced murine Lhb promoter activity; this species-specific difference depends on SMAD-binding elements (SBEs) present in the murine but not human promoter. Co-immunoprecipitation, domain mapping, promoter reporter assays, SBE site-directed mutagenesis, ChIP Cellular signalling High 20149866
2011 EGR1 directly binds to the heparanase gene promoter via two functional EGR1 sites and activates its expression in cancer cells; EGR1-driven chromatin remodeling and transactivation of HPSE is potentiated by p300-mediated activation (in the hnRNPU/p300/EGR1/HPSE axis). ChIP assay, luciferase reporter, co-IP (EGR1–p300/CBP interaction verified) Oncogene Medium 29511351
2023 EGR1 physically interacts with p300/CBP (verified by co-IP) and together transcriptionally activates SNAI2 (Slug) promoter, driving EMT and invasion in pancreatic cancer; EGR1 binding to the SNAI2 promoter was confirmed by ChIP-qPCR. Co-IP (EGR1–p300/CBP), ChIP-qPCR (EGR1 at SNAI2 promoter), dual-luciferase reporter, Transwell invasion assay, in vivo liver metastasis model Journal of translational medicine Medium 36932397
2015 EGR1 directly binds the proximal promoter of Per1 to activate its transcription; EGR1 is itself transactivated by the CLOCK/BMAL1 heterodimer through a conserved E-box; in Egr1-/- mice the amplitude (but not phase) of hepatic clock genes including Bmal1, Per1, Per2, Rev-erbα/β is reduced. ChIP (EGR1 at Per1 promoter), luciferase reporter assay (E-box CLOCK/BMAL1 transactivation), Egr1-/- mouse circadian gene expression analysis Scientific reports High 26471974
2021 In differentiating macrophages, EGR1 binds inflammatory enhancers (many without its canonical motif) and represses inflammatory genes through the NuRD corepressor complex; in monocytes, EGR1 binds enhancers regulating developmental genes like CSF1R. EGR1 ChIP-seq (monocytes vs macrophages), ATAC-seq, NuRD complex co-immunoprecipitation, EGR1 knockdown with inflammatory gene expression readout Science advances High 33523892
2009 Mutant EGFR (delE746_A750) constitutively upregulates EGR1 expression through the ERK (MEK/ERK) pathway, not through PI3K; MEK inhibitor U0126 blocks EGR1 expression in mutant EGFR cells, while PI3K inhibitor LY294002 does not. Gene expression profiling, RT-PCR/immunoblotting, MEK inhibitor (U0126), PI3K inhibitor (LY294002), EGFR-TKI treatment Anticancer research Medium 19414352
2021 EGR1 is a downstream effector of B-cell receptor/JAK1 signaling in DLBCL; EGR1 upregulates MYC and E2F pathway genes through the CBP/p300/H3K27ac/BRD4 axis and represses type I IFN pathway genes by interacting with corepressor NAB2. EGR1 ChIP-seq, H3K27ac ChIP-seq, co-IP (EGR1–NAB2, EGR1–CBP/p300), EGR1 knockdown/knockout, xenograft mouse models Molecular cancer research : MCR High 33980611
2018 EGR1 acts as a transcriptional activator of KLK7 through direct binding to the EBS in the KLK7 proximal promoter in response to IL-13; ERK1/2 MAPK pathway is required for IL-13-induced EGR1-dependent KLK7 transcription; Egr1-/- mice lack IL-13/DNCB-induced KLK7 expression in AD-like skin lesions. Promoter reporter assay (EBS point mutation), ChIP (EGR1 at KLK7 promoter), EGR1 shRNA knockdown, Egr1-/- mice, ERK1/2 inhibitor experiments Biochemical and biophysical research communications High 33276948
2019 EGR1 is a direct transcriptional activator of leptin gene expression in breast cancer cells; the EGR1-binding motif in the proximal leptin promoter is required for TNF-α-induced leptin transcription (shown by point mutation); EGR1 overexpression activates leptin promoter and EGR1 knockdown reduces TNF-α-induced leptin accumulation; ERK1/2 pathway mediates this response. Promoter reporter assay (EBS point mutation), EGR1 overexpression, EGR1 siRNA knockdown, ERK1/2 pathway inhibition Molecular biology reports Medium 30417207
2022 EGR1 directly binds the Sox9 gene promoter and activates SOX9 expression in renal tubular cells; EGR1-induced SOX9 promotes tubular cell proliferation through the Wnt/β-catenin pathway; genetic Egr1 knockout aggravates AKI severity in mouse models. ChIP assay (EGR1 at Sox9 promoter), dual-luciferase reporter, Egr1-/- mice with IRI and nephrotoxic AKI models, RNA sequencing Theranostics High 35910788
2019 EGR1 directly binds the METTL3 promoter (confirmed by ChIP) to transcriptionally activate METTL3 expression; METTL3-mediated m6A modification of VIM mRNA downregulates VIM expression, thereby protecting hippocampal neurons from injury in epilepsy. ChIP assay (EGR1 at METTL3 promoter), EGR1/METTL3/VIM knockdown in epilepsy cell and mouse models, m6A modification assay Neurochemical research Medium 37268752
2024 EGR1 directly binds the PFKL (phosphofructokinase-1, liver type) promoter and represses PFKL gene expression, thereby inhibiting aerobic glycolysis and suppressing hepatocellular carcinoma growth; EGR1 overexpression in mouse HCC models and human hepatoma organoids validated this tumor-suppressive mechanism. ChIP (EGR1 at PFKL promoter), EGR1 overexpression/knockdown in vitro and in vivo, xenograft tumor model, human hepatoma organoid, glycolysis assays Journal of experimental & clinical cancer research : CR Medium 38287371
2015 EGR1 regulates ATGL (adipose triglyceride lipase) expression and fat storage in adipocytes; EGR1 protein expression is predominantly regulated via the mTORC1/4E-BP translational axis rather than transcriptionally; 4E-BP1/2 knockout cells translate Egr1 mRNA more efficiently, express less ATGL, and accumulate more fat. 35S-labeling (translational efficiency), MEK inhibitor/mTORC1 inhibitor pharmacology, 4E-BP1/2-null and TSC2-null MEFs, ATGL expression and fat accumulation assays The Journal of biological chemistry Medium 25814662
2019 EGR1 transcriptionally activates TFEB expression by directly binding the TFEB promoter; in the absence of EGR1, the TFEB-mediated transcriptional response to starvation is impaired; pharmacological inhibition of EGR1 (via MEK1/2 inhibitor Trametinib) reduces proliferation of cells with constitutive TFEB activation. EGR1 ChIP-seq (EGR1 at TFEB promoter), EGR1 genetic knockout, MEK1/2 inhibitor (Trametinib), 3D culture proliferation assay, BHD patient-derived cells PLoS biology High 36888606
2018 EGR1 interacts with TBX2 (co-immunoprecipitation); TBX2 binding inhibits EGR1-dependent transcription of target genes including p21 (CDKN1A), PTEN, NDRG1, and CST6; EGR1 overexpression in ARMS cells reduces proliferation and induces apoptosis via the intrinsic pathway (BAX activation, BAD dephosphorylation). Co-immunoprecipitation (EGR1-TBX2), EGR1 overexpression, reporter gene assays, apoptosis flow cytometry, western blot Oncotarget Medium 29719592
2022 EGR1 controls TET2 recruitment to the MIF promoter through protein-protein interaction; TET2 downregulation disrupts this interaction with EGR1 and histone deacetylases at the MIF promoter, leading to enhanced EGR1-driven MIF transcription and MIF secretion in resting monocytes. ChIP (TET2, EGR1 at MIF promoter), co-IP (TET2-EGR1-HDAC complex), TET2 knockdown in mouse and human cells, MIF secretion ELISA Communications biology Medium 35115654
2022 Egr1 is required for dopaminergic signaling during social behavior in zebrafish; egr1 mutant fish show reduced social approach and tyrosine hydroxylase (TH) expression is markedly decreased in TH-positive neurons of the anterior parvocellular preoptic nucleus; chemogenetic ablation of ~30% of these TH+ neurons phenocopies the egr1 social behavior deficit. Egr1 zebrafish mutant (loss-of-function), in situ hybridization for TH, chemogenetic neuronal ablation, behavioral assays eNeuro Medium 35346959
2024 Egr1 regulates regenerative senescence in the adult mouse heart; in cardiac fibroblasts, Egr1 is activated by the integrin-FAK-ERK-Akt1 signaling axis in response to agrin; Egr1 facilitates angiogenesis and cardiomyocyte proliferation in neonatal hearts and is required for agrin-induced senescence-mediated cardiac repair in adult mice. Proteomics, single-cell RNA sequencing, Egr1 conditional KO in cardiac fibroblasts, agrin-treatment mouse model, pathway inhibition (FAK-ERK-Akt1) Nature cardiovascular research High 39196027
2019 EGR1 binds the viral genome upstream of the CMV UL138 latency gene and is sufficient to promote UL138 expression; disruption of EGR1 binding upstream of UL138 prevents the establishment of CMV latency in CD34+ hematopoietic progenitor cells; EGR1 is induced downstream of EGFR/MEK/ERK signaling in HPCs. EGR1 ChIP on viral genome, EGR1 overexpression (sufficient for UL138 induction), mutation of EGR1 binding site in viral genome, CMV latency assay in CD34+ HPCs PLoS pathogens High 31725811
2019 EGR1 transcriptionally activates GnRH-responsive AMH receptor type 2 (AMHR2) expression in gonadotrope cells; EGR1 mediates both basal and GnRH-dependent AMHR2 promoter activity through a proximal -53/-37 bp binding site; FOXO1 acts as a negative regulator of EGR1-dependent AMHR2 expression. Promoter deletion constructs, site-directed mutagenesis of Egr1 motif, siRNA knockdown of Egr1, constitutively active FOXO1 mutant, perifusion of LβT2 gonadotrope cells Neuroendocrinology Medium 30368511
2020 EGR1 directly activates CCND1 (cyclin D1) promoter transcription (confirmed by ChIP assay with EGF stimulation); EGR1 silencing inhibits glioma cell proliferation and induces G1 phase arrest, establishing EGR1-CCND1 as a proliferative axis in glioma. ChIP assay (EGR1 at CCND1 promoter), siRNA EGR1 knockdown, cell cycle analysis, proliferation assays in U251/U87 cells and in vivo xenograft Journal of experimental & clinical cancer research : CR Medium 29246166
1998 Targeted disruption of Egr-1 (Krox-24) in mice causes sterility and reduced body size; specifically, Egr-1 null gonadotropes fail to synthesize the LHβ subunit and somatotropes are reduced in number, indicating EGR1 is required for LHβ transcription in gonadotropes and for somatotrope proliferation/survival. Gene targeting (null allele), histopathology, immunohistochemistry, hormone measurement in Egr1-/- mice Molecular endocrinology (Baltimore, Md.) High 9440815
2019 EGR1 directly upregulates p53 transcription by binding the p53 promoter; EGR1 promotes p53-dependent apoptosis in retinal vascular endothelial cells under high-glucose conditions; downregulation of Egr1 reduces apoptosis and tube formation in vivo through p53 reduction. EGR1 shRNA knockdown, p53 overexpression rescue, in vivo sh-Egr1 delivery in diabetic rats, apoptosis/tube formation assays Journal of cellular and molecular medicine Medium 30887692
2019 EGR1 identified as a novel splicing isoform: a shorter EGR1 protein lacking part of the N-terminal activation domain can enter the nucleus but cannot fully activate transcription compared to canonical EGR1. RT-PCR cloning of novel transcript, nuclear localization assay, transcriptional activation reporter assay International journal of molecular sciences Low 30925677
2022 EGR1 promotes hepatoprotection in acetaminophen-induced liver injury by transcriptionally upregulating Acaa2 (a key gene for mitochondrial fatty acid β-oxidation); liver-specific Egr1 knockout worsens AILI while adenoviral EGR1 overexpression ameliorates it; Acaa2 knockdown abolishes EGR1's protective effect. Liver-specific Egr1-KO mice, adenoviral EGR1 overexpression, ChIP-seq (EGR1 at Acaa2 locus), RNA-seq, Seahorse metabolic assay, Acaa2 siRNA knockdown International journal of biological sciences High 35813467
2020 RUNX2 and EGR1 co-occupy Htra1 enhancers in osteoblasts (validated by Re-ChIP assay) and together co-repress Htra1 while promoting expression of osterix, osteocalcin, and osteoprotegerin; co-knockdown of RUNX2 and EGR1 reduces osteoblast calcification and ALP activity. RUNX2 ChIP-seq, RNA-seq (Runx2 heterozygous mice), dual-luciferase enhancer assays, Re-ChIP (RUNX2+EGR1 co-occupancy), siRNA double knockdown, Alizarin red/ALP staining Journal of cellular physiology Medium 32324256

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 NAB2, a corepressor of NGFI-A (Egr-1) and Krox20, is induced by proliferative and differentiative stimuli. Molecular and cellular biology 329 8668170
2004 A gene for neuronal plasticity in the mammalian brain: Zif268/Egr-1/NGFI-A/Krox-24/TIS8/ZENK? Progress in neurobiology 312 15556287
1995 DNA-binding specificity of NGFI-A and related zinc finger transcription factors. Molecular and cellular biology 298 7891721
2017 The Role of Early Growth Response 1 (EGR1) in Brain Plasticity and Neuropsychiatric Disorders. Frontiers in behavioral neuroscience 284 28321184
1995 Identification of NAB1, a repressor of NGFI-A- and Krox20-mediated transcription. Proceedings of the National Academy of Sciences of the United States of America 240 7624335
1998 Multiple pituitary and ovarian defects in Krox-24 (NGFI-A, Egr-1)-targeted mice. Molecular endocrinology (Baltimore, Md.) 233 9440815
2021 The Role of the Transcription Factor EGR1 in Cancer. Frontiers in oncology 221 33842351
2013 Transcription factor EGR1 directs tendon differentiation and promotes tendon repair. The Journal of clinical investigation 201 23863709
2005 The MAPK pathway and Egr-1 mediate stress-related behavioral effects of glucocorticoids. Nature neuroscience 195 15834420
2010 EGR1 and EGR2 involvement in vertebrate tendon differentiation. The Journal of biological chemistry 166 21173153
1995 Growth and differentiation proceeds normally in cells deficient in the immediate early gene NGFI-A. The Journal of biological chemistry 153 7730380
1989 Structure of the NGFI-A gene and detection of upstream sequences responsible for its transcriptional induction by nerve growth factor. Proceedings of the National Academy of Sciences of the United States of America 153 2492104
2014 The transcription factor Zif268/Egr1, brain plasticity, and memory. Progress in molecular biology and translational science 151 24484699
2001 Impaired prostate tumorigenesis in Egr1-deficient mice. Nature medicine 150 11135623
2019 EGR1 regulates angiogenic and osteoclastogenic factors in prostate cancer and promotes metastasis. Oncogene 128 31312026
2021 EGR1 is a gatekeeper of inflammatory enhancers in human macrophages. Science advances 127 33523892
2012 Maternal licking regulates hippocampal glucocorticoid receptor transcription through a thyroid hormone-serotonin-NGFI-A signalling cascade. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 123 22826348
2019 EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity. Nature communications 119 31467272
2008 PTEN regulation by Akt-EGR1-ARF-PTEN axis. The EMBO journal 116 19057511
2011 Actinium-225 in targeted alpha-particle therapeutic applications. Current radiopharmaceuticals 114 22202153
2016 A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer. Nature communications 104 27041221
1991 5' upstream sequence and genomic structure of the human primary response gene, EGR-1/TIS8. Oncogene 104 2052361
2009 Is EGR1 a potential target for prostate cancer therapy? Future oncology (London, England) 99 19792968
1998 Nab1, a corepressor of NGFI-A (Egr-1), contains an active transcriptional repression domain. Molecular and cellular biology 98 9418898
2018 HPSE enhancer RNA promotes cancer progression through driving chromatin looping and regulating hnRNPU/p300/EGR1/HPSE axis. Oncogene 93 29511351
1996 Unimpaired macrophage differentiation and activation in mice lacking the zinc finger transplantation factor NGFI-A (EGR1). Molecular and cellular biology 89 8754857
2006 A network of p73, p53 and Egr1 is required for efficient apoptosis in tumor cells. Cell death and differentiation 88 16990849
1993 Transcriptional activity of the zinc finger protein NGFI-A is influenced by its interaction with a cellular factor. Molecular and cellular biology 88 8413279
1990 Expression of the nerve growth factor-regulated NGFI-A and NGFI-B genes in the developing rat. Development (Cambridge, England) 86 2081458
2023 Nuclear PD-L1 promotes EGR1-mediated angiogenesis and accelerates tumorigenesis. Cell discovery 81 36977660
2020 EGR1-mediated linc01503 promotes cell cycle progression and tumorigenesis in gastric cancer. Cell proliferation 81 33145887
2005 Ethanol-induced liver injury: potential roles for egr-1. Alcoholism, clinical and experimental research 79 16344600
2005 Early growth response gene 1 (EGR1) regulates heparanase gene transcription in tumor cells. The Journal of biological chemistry 76 16093249
2014 Expression, regulation and function of Egr1 during implantation and decidualization in mice. Cell cycle (Georgetown, Tex.) 66 25486203
2019 Friend or foe, the role of EGR-1 in cancer. Medical oncology (Northwood, London, England) 63 31748910
2019 Host signaling and EGR1 transcriptional control of human cytomegalovirus replication and latency. PLoS pathogens 61 31725811
2022 Transient upregulation of EGR1 signaling enhances kidney repair by activating SOX9+ renal tubular cells. Theranostics 59 35910788
2017 Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy. PLoS biology 54 28358805
2024 EGR1 suppresses HCC growth and aerobic glycolysis by transcriptionally downregulating PFKL. Journal of experimental & clinical cancer research : CR 50 38287371
2017 Inhibition of EGR1 inhibits glioma proliferation by targeting CCND1 promoter. Journal of experimental & clinical cancer research : CR 50 29246166
2018 MicroRNA-181a-5p suppresses cell proliferation by targeting Egr1 and inhibiting Egr1/TGF-β/Smad pathway in hepatocellular carcinoma. The international journal of biochemistry & cell biology 49 30503931
2019 Egr1 mediates retinal vascular dysfunction in diabetes mellitus via promoting p53 transcription. Journal of cellular and molecular medicine 47 30887692
2003 Egr1 signaling in prostate cancer. Cancer biology & therapy 44 14688464
2022 Examining the role of EGR1 during viral infections. Frontiers in microbiology 42 36338037
2014 The methylated-DNA binding protein MBD2 enhances NGFI-A (egr-1)-mediated transcriptional activation of the glucocorticoid receptor. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 42 25135974
2019 Targeted alpha therapy with bismuth-213 and actinium-225: Meeting future demand. Journal of labelled compounds & radiopharmaceuticals 41 31369165
2012 Consistency test of the cell cycle: roles for p53 and EGR1. Cancer research 41 22315347
2008 Egr1 regulates the coordinated expression of numerous EGF receptor target genes as identified by ChIP-on-chip. Genome biology 39 19032775
2020 225Ac- and 213Bi-Substance P Analogues for Glioma Therapy. Seminars in nuclear medicine 38 32172799
2023 EGR1 induces EMT in pancreatic cancer via a P300/SNAI2 pathway. Journal of translational medicine 37 36932397
2005 Mechanisms of prostate tumorigenesis: roles for transcription factors Nkx3.1 and Egr1. Annals of the New York Academy of Sciences 37 16382041
2015 EGR1 regulates hepatic clock gene amplitude by activating Per1 transcription. Scientific reports 35 26471974
1997 Increased expression of NGFI-A mRNA in the rat striatum following burst stimulation of the medial forebrain bundle. The European journal of neuroscience 35 9464931
2011 Coordinated sumoylation and ubiquitination modulate EGF induced EGR1 expression and stability. PloS one 34 21998680
2022 [225Ac]Ac-SibuDAB for Targeted Alpha Therapy of Prostate Cancer: Preclinical Evaluation and Comparison with [225Ac]Ac-PSMA-617. Cancers 33 36428743
2022 EGR1 Upregulation during Encephalitic Viral Infections Contributes to Inflammation and Cell Death. Viruses 32 35746681
1999 Expression of c-fos, NGFI-A and secretogranin II mRNA in brain regions during initiation of cocaine self-administration in mice. The European journal of neuroscience 32 10564376
2021 Early growth response 1 (EGR1) activation in initial stages of host-pathogen interactions. Molecular biology reports 30 33783681
1997 NGFI-A expression in the rat brain after sleep deprivation. Brain research. Molecular brain research 30 9191088
2018 EGR1 interacts with TBX2 and functions as a tumor suppressor in rhabdomyosarcoma. Oncotarget 29 29719592
2009 EGFR mutation up-regulates EGR1 expression through the ERK pathway. Anticancer research 29 19414352
2008 Egr1 involvement in evening gene regulation by melatonin. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 29 19019852
2024 Egr1 regulates regenerative senescence and cardiac repair. Nature cardiovascular research 28 39196027
2022 Macrophage migration inhibitory factor is overproduced through EGR1 in TET2low resting monocytes. Communications biology 25 35115654
2015 4E-BPs Control Fat Storage by Regulating the Expression of Egr1 and ATGL. The Journal of biological chemistry 25 25814662
1997 5-Hydroxytryptamine induces TIS8/egr-1 and c-fos expression in PC12 cells. Involvement of tyrosine protein phosphorylation. The European journal of neuroscience 25 9042572
2022 Egr1 confers protection against acetaminophen‑induced hepatotoxicity via transcriptional upregulating of Acaa2. International journal of biological sciences 24 35813467
2017 Phosphorylation of Serine 225 in Hepatitis C Virus NS5A Regulates Protein-Protein Interactions. Journal of virology 24 28615203
2013 Changes in the Egr1 and Arc expression in brain structures of pentylenetetrazole-kindled rats. Pharmacological reports : PR 24 23744421
2002 Expression of the zinc finger Egr1 gene during zebrafish embryonic development. Mechanisms of development 24 12351200
1999 Involvement of the NGFI-A gene in the differentiation of neuroblastoma cells. FEBS letters 24 10561492
2022 Nitroxoline suppresses metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway. International journal of biological sciences 22 35982887
2020 Evaluation of Actinium-225 Labeled Minigastrin Analogue [225Ac]Ac-DOTA-PP-F11N for Targeted Alpha Particle Therapy. Pharmaceutics 22 33198403
2009 Early growth response 1 (EGR1): a gene with as many names as biological functions. Cancer biology & therapy 22 20009530
1998 Kindling and associated mossy fibre sprouting are not affected in mice deficient of NGFI-A/NGFI-B genes. Neuroscience 22 9466414
2021 Chrysin Inhibits TNFα-Induced TSLP Expression through Downregulation of EGR1 Expression in Keratinocytes. International journal of molecular sciences 21 33919431
2019 Glucocorticoids delay RAF-induced senescence promoted by EGR1. Journal of cell science 21 31371485
2022 Egr1 Is Necessary for Forebrain Dopaminergic Signaling during Social Behavior. eNeuro 20 35346959
2018 GnRH Transactivates Human AMH Receptor Gene via Egr1 and FOXO1 in Gonadotrope Cells. Neuroendocrinology 20 30368511
2010 SMAD3 and EGR1 physically and functionally interact in promoter-specific fashion. Cellular signalling 20 20149866
2014 Egr-1 upregulates Siva-1 expression and induces cardiac fibroblast apoptosis. International journal of molecular sciences 19 24451137
2000 Cyclical expression of egr-1/NGFI-A in the rat anterior pituitary: a molecular signal for ovulation? Journal of neuroendocrinology 19 10849212
2021 DNA-PKcs kinase activity stabilizes the transcription factor Egr1 in activated immune cells. The Journal of biological chemistry 18 34562454
2008 Evaluation of EGR1 as a candidate gene for high myopia. Molecular vision 18 18636116
2022 LncRNA-COX2 inhibits Fibroblast Activation and Epidural Fibrosis by Targeting EGR1. International journal of biological sciences 17 35280679
2020 RUNX2 co-operates with EGR1 to regulate osteogenic differentiation through Htra1 enhancers. Journal of cellular physiology 17 32324256
2019 TBA225, a fusion toxoid vaccine for protection and broad neutralization of staphylococcal superantigens. Scientific reports 17 30824769
2023 DDIT3 aggravates pulpitis by modulating M1 polarization through EGR1 in macrophages. International immunopharmacology 16 37235961
2023 EGR1-Driven METTL3 Activation Curtails VIM-Mediated Neuron Injury in Epilepsy. Neurochemical research 16 37268752
2018 Leptin is a direct transcriptional target of EGR1 in human breast cancer cells. Molecular biology reports 16 30417207
2023 EGR1 drives cell proliferation by directly stimulating TFEB transcription in response to starvation. PLoS biology 15 36888606
2023 Actinium-225 Targeted Agents: Where Are We Now? Brachytherapy 15 37690972
2021 EGR1 Addiction in Diffuse Large B-cell Lymphoma. Molecular cancer research : MCR 15 33980611
2019 Functional analyses and effect of DNA methylation on the EGR1 gene in patients with schizophrenia. Psychiatry research 15 30952071
2019 Identification, Characterization, and Regulatory Mechanisms of a Novel EGR1 Splicing Isoform. International journal of molecular sciences 14 30925677
2007 Differential expression of egr1 and activation of microglia following irradiation in the rat brain. Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 14 17497096
2022 Cyclic mechanical stretch regulates the AMPK/Egr1 pathway in tenocytes via Ca2+-mediated mechanosensing. Connective tissue research 13 35229695
2020 Loss of EGR-1 uncouples compensatory responses of pancreatic β cells. Theranostics 13 32226550
2020 Altered light induced EGR1 expression in the SCN of PACAP deficient mice. PloS one 13 32379800
2020 EGR-1 acts as a transcriptional activator of KLK7 under IL-13 stimulation. Biochemical and biophysical research communications 13 33276948

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