Affinage

ELF3

ETS-related transcription factor Elf-3 · UniProt P78545

Length
371 aa
Mass
41.5 kDa
Annotated
2026-06-09
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ELF3 (ESE-1/ERT) is an epithelium-specific ETS-family transcription factor that programs epithelial differentiation and links pro-inflammatory signaling to target-gene control through sequence-specific binding at ETS sites (PMID:9234700, PMID:9417054). Its bipartite DNA-binding architecture combines an ETS domain with an A/T-hook, with the transactivation function residing in the amino terminus (PMID:9234700, PMID:9417054). As a context-dependent regulator it activates differentiation and signaling genes—SPRR2A and keratin K12 in keratinocyte/corneal differentiation, the TGF-β type II receptor to restore TGF-β growth suppression, and angiopoietin-1 and COX-2 in inflammation—while acting as a direct repressor of others such as COL2A1, MMP-9, and the miR-141/miR-144 microRNAs that gate ZEB1-driven EMT (PMID:9234700, PMID:9417054, PMID:10644990, PMID:11025204, PMID:14715662, PMID:15794755, PMID:18044710, PMID:18302674, PMID:29523781, PMID:35616822). ELF3 is itself an inflammatory effector: pro-inflammatory cytokines (IL-1β, TNF-α, IL-17A) induce its expression through NF-κB and the co-factor IκBζ, and Elf3-deficient mice show altered cytokine output and skewed dendritic-cell–driven T-cell differentiation (PMID:12746898, PMID:18475289, PMID:21948981, PMID:35792833). A distinctive feature is compartment-dependent dual function: nuclear ELF3 acts transcriptionally and can drive apoptosis, whereas cytoplasmic ELF3 transforms mammary epithelial cells through its serine/aspartate-rich (SAR) domain by a non-transcriptional mechanism, with localization governed by an A/T-hook NLS and two CRM1-dependent nuclear export signals (PMID:15169914, PMID:21871131). ELF3 also represses androgen receptor activity by physically interacting with AR and blocking its promoter recruitment (PMID:23435425). Upstream, ELF3 is positioned within a RIPK4→IRF6→GRHL3 keratinocyte cornification hierarchy and is controlled by super-enhancers, m6A modification (WTAP), and autoregulatory feedback at its own promoter (PMID:27667567, PMID:33622787, PMID:38481803). Across cancers ELF3 has both tumor-suppressive (TGF-β RII restoration, EREG/EGFR-mTORC1 repression) and oncogenic (LUAD amplification, ASCL1+ neuroendocrine super-enhancer network, hypoxic IGF1/VEGF angiogenesis) roles depending on tissue context (PMID:10644990, PMID:31780666, PMID:35695065, PMID:37345534, PMID:36840413).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1997 High

    Established the founding identity of ELF3 as an epithelium-restricted ETS transcription factor with a unique two-domain DNA-binding architecture, answering what kind of regulatory protein it is.

    Evidence Molecular cloning, EMSA, and reporter assays on the SPRR2A promoter and Endo A enhancer

    PMID:9234700

    Open questions at the time
    • Direct in vivo target repertoire not yet defined
    • Role of the A/T-hook versus ETS domain in target selection not dissected
  2. 1998 High

    Identified TGF-β type II receptor as a direct ELF3 target and mapped functional domains, connecting ELF3 to growth-suppressive signaling.

    Evidence Yeast one-hybrid, EMSA, reporter assays, and deletion mapping on the TGF-β RII promoter

    PMID:9417054

    Open questions at the time
    • Physiological consequence of TGF-β RII activation not tested in this study
  3. 2000 High

    Demonstrated that ELF3 restores TGF-β growth-inhibitory signaling and reduces tumorigenicity, establishing a tumor-suppressive axis in breast cancer.

    Evidence Retroviral overexpression, Northern blot, and xenograft assays in Hs578t cells

    PMID:10644990

    Open questions at the time
    • Whether endogenous ELF3 loss drives the tumor phenotype not addressed
    • Mechanism of TGF-β RII silencing not resolved
  4. 2000 Medium

    Linked ELF3 to epithelial differentiation programs beyond skin, showing it drives corneal keratin expression and is required for corneal epithelial differentiation.

    Evidence Reporter assays and antisense loss-of-function in corneal epithelial cells

    PMID:11025204

    Open questions at the time
    • Antisense specificity limited
    • Direct binding to K12 element vs. indirect effect not separated
  5. 2003 High

    Defined how inflammation engages ELF3, showing IL-1β induces ELF3 via direct NF-κB binding to its promoter, casting ELF3 as a downstream inflammatory effector.

    Evidence Reporter mutants, EMSA supershift, adenoviral IκB, and ChIP in primary cells

    PMID:12746898

    Open questions at the time
    • Downstream inflammatory targets not yet enumerated in this study
  6. 2003 Medium

    Showed ELF3 operates within multi-factor differentiation complexes, cooperating with Skn-1a to drive SPRR2A.

    Evidence Co-transfection reporter assays and domain mapping

    PMID:12624109

    Open questions at the time
    • Physical interaction with Skn-1a not directly shown
    • Cooperativity not validated at endogenous loci
  7. 2004 High

    Defined ELF3 as a direct activator of pro-inflammatory/angiogenic genes (Ang-1, and later COX-2), expanding its inflammatory transcriptional program.

    Evidence Promoter mutagenesis, EMSA, transcriptional profiling, and dominant-negative assays

    PMID:14715662 PMID:15794755

    Open questions at the time
    • In vivo requirement of ELF3 for Ang-1/COX-2 induction not tested
  8. 2004 High

    Revealed a compartment-specific dual mechanism: cytoplasmic ELF3 transforms via the SAR domain non-transcriptionally while nuclear ELF3 induces apoptosis transcriptionally.

    Evidence GFP localization, NLS/NES fusions, domain deletion, and transformation/apoptosis assays in mammary epithelial cells

    PMID:15169914

    Open questions at the time
    • Cytoplasmic SAR-domain effector partners not identified
    • Endogenous relevance of cytoplasmic pool not established
  9. 2008 High

    Established ELF3 as a direct transcriptional repressor in addition to an activator, repressing COL2A1 and MMP-9 and extending the cytokine-driven NF-κB induction to airway epithelium.

    Evidence ChIP, EMSA, siRNA, reporter mapping, invasion/zymography assays, and Elf3 KO mice

    PMID:18044710 PMID:18302674 PMID:18475289

    Open questions at the time
    • Determinants of activator vs. repressor mode at a given promoter not defined
    • Negative autoregulation mechanism partial
  10. 2008 High

    Connected ELF3 to drug-induced apoptosis via EGR-1 and showed pharmacological control of its nuclear translocation.

    Evidence EMSA, ChIP, reporter, siRNA, and nuclear translocation assays in colorectal cancer cells

    PMID:19074849

    Open questions at the time
    • Signal coupling tolfenamic acid to ELF3 translocation not resolved
  11. 2011 High

    Mapped the NLS/NES architecture controlling ELF3 localization and pinpointed NES2 as essential for SAR-domain transformation.

    Evidence GFP localization, site-directed mutagenesis of NLS/NES motifs, and transformation assays

    PMID:21871131

    Open questions at the time
    • Physiological signals regulating CRM1-dependent export not identified
  12. 2011 High

    Defined ELF3's organismal immune role, showing it controls dendritic-cell IL-12p40/IL-6 output and Th1/Th17 versus Th2 balance.

    Evidence Elf3 knockout mice, OVA airway models, ELISA, and flow cytometry

    PMID:21948981

    Open questions at the time
    • Direct ELF3 binding at IL-12p40 not demonstrated
    • Cell-intrinsic vs extrinsic contributions not fully separated
  13. 2013 High

    Uncovered a non-ETS-DNA mechanism of action: ELF3 physically binds the androgen receptor and blocks its promoter recruitment, repressing AR signaling.

    Evidence Co-IP/pulldown, ChIP of AR recruitment, siRNA/overexpression, and xenografts in prostate cancer

    PMID:23435425

    Open questions at the time
    • Interaction interface on ELF3/AR not mapped
    • Whether other nuclear receptors are similarly inhibited unknown
  14. 2016 Medium

    Placed ELF3 within an upstream keratinocyte cornification signaling hierarchy (RIPK4→IRF6→GRHL3→ELF3).

    Evidence Sequential siRNA epistasis, qRT-PCR, and Western blot in keratinocytes

    PMID:27667567

    Open questions at the time
    • Direct vs. indirect regulation of ELF3 by IRF6/GRHL3 not distinguished
    • Single-lab epistasis
  15. 2018 Medium

    Defined ELF3's role in EMT control by repressing ZEB1-activating microRNAs and antagonizing Wnt/RAS signaling, revealing context-dependent pro- and anti-EMT effects.

    Evidence ChIP at miR-141-3p promoter, RNA-seq, siRNA, and migration/invasion assays in liver and colorectal cancer

    PMID:29523781 PMID:30148686

    Open questions at the time
    • Opposing EMT directions across cancers not mechanistically reconciled
    • Direct binding shown only in some contexts
  16. 2019 Medium

    Demonstrated ELF3 can act as an amplified oncogenic driver dependent on tissue context in lung adenocarcinoma.

    Evidence Genomic copy-number/methylation analysis and functional knockdown with tumor growth readout

    PMID:31780666

    Open questions at the time
    • Oncogenic transcriptional targets in LUAD not defined here
    • Mechanism of subtype specificity unresolved
  17. 2021 High

    Revealed super-enhancer and autoregulatory control of ELF3 plus a MED-coactivator interaction required for HLA-C expression in trophoblasts.

    Evidence ChIP-PCR, siRNA, ATAC-seq, single-cell RNA-seq, and wrenchnolol disruption of ELF3-MED23

    PMID:33622787

    Open questions at the time
    • Generality of the autoregulatory loop beyond trophoblasts unknown
    • MED23 vs MED1 contributions not fully separated
  18. 2022 Medium

    Extended ELF3 functions to hypoxic angiogenesis (IGF1/VEGF) and to vertebrate ECM/tissue morphogenesis.

    Evidence siRNA, ELISA, angiogenesis/xenograft assays in ovarian cancer; morpholino and CRISPR knockdown phenotyping in zebrafish

    PMID:35695065 PMID:36383615

    Open questions at the time
    • Direct ELF3 binding to IGF1 promoter not fully confirmed
    • ECM target genes downstream of Elf3 in zebrafish not directly bound
  19. 2023 High

    Consolidated ELF3 as a bidirectional cancer regulator: tumor-suppressive via direct EREG repression limiting EGFR/mTORC1, and oncogenic via a super-enhancer-driven network in ASCL1+ neuroendocrine carcinoma.

    Evidence Autochthonous KPCE mouse model, organoids, ChIP, CRISPR epistasis (gallbladder); ATAC-seq, CUT&Tag, and KD-RNA-seq (neuroendocrine carcinoma)

    PMID:36840413 PMID:37345534

    Open questions at the time
    • What dictates suppressor vs. oncogene behavior across lineages unresolved
    • Cooperating factors in the NEC network not mapped
  20. 2024 Medium

    Identified post-transcriptional (m6A/WTAP) control of ELF3 and new direct targets driving fibroblast senescence (IRF8) and copper-dependent cell death (SLC31A1).

    Evidence m6A-seq, ChIP at IRF8 and SLC31A1 promoters, reporter assays, sh/siRNA, and in vivo aging/AKI models

    PMID:38462020 PMID:38481803

    Open questions at the time
    • Reader/eraser logic of ELF3 m6A regulation incomplete
    • Single-lab target validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what molecular switch determines ELF3's opposing transcriptional outputs—activator vs. repressor at a given promoter, and tumor-suppressor vs. oncogene across tissues—and how its nuclear/cytoplasmic partitioning is dynamically controlled in vivo.
  • No unified model of cofactor-dependent activator/repressor switching
  • Cytoplasmic SAR-domain effector pathway uncharacterized
  • Genome-wide direct binding map across cell types absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1643685 Disease 5 R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 4
Partners
ARMED1MED23WTAP

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 ELF3 (ESE-1) was identified as an epithelium-specific ETS transcription factor containing two DNA-binding domains: an ETS domain and an A/T hook domain (found in HMG proteins). It binds with high affinity to ETS binding sites in the SPRR2A promoter and transactivates SPRR2A and the Endo A gene enhancer, establishing it as a transcriptional activator of keratinocyte differentiation target genes. Molecular cloning, electrophoretic mobility shift assay (EMSA), transient transfection/luciferase reporter assay Molecular and cellular biology High 9234700
1998 ELF3 (ERT) activates transcription of the TGF-β type II receptor (RII) gene by binding to ETS binding sites in the TGF-β RII promoter (response element at +13 to +24 and multiple sites between -1816 and -82). Deletion mapping showed the transactivation domain resides in the amino terminus and the DNA-binding domain in the carboxyl-terminal region. Yeast one-hybrid screening, luciferase reporter assay, EMSA, deletion mapping The Journal of biological chemistry High 9417054
1999 The human ELF3 gene contains nine exons spanning ~5.8 kb. A 1.5-kb fragment of the 5' upstream region acts as a functional promoter in epithelial cell lines, containing TATA and CCAAT boxes and potential binding sites for Ets factors and NF-κB. Genomic cloning, transfection experiments with promoter-reporter constructs Genomics Medium 10049594
2000 ELF3 (ERT) overexpression in Hs578t breast cancer cells induces endogenous TGF-β type II receptor mRNA and protein expression, restores TGF-β growth inhibitory signaling (~50% growth reduction with exogenous TGF-β1), and reduces tumorigenicity in athymic mice, confirming ELF3 as a transcriptional activator of TGF-β RII in vivo. Retroviral overexpression, Northern blot, luciferase reporter assay, xenograft mouse model Oncogene High 10644990
2000 ELF3 (ESE-1) is expressed in corneal epithelial cells and is upregulated during differentiation. It transactivates the regulatory element of cornea-specific K12 keratin. Introduction of ESE-1 antisense RNA in immortalized human corneal epithelial cells impairs their differentiation. Northern blot, luciferase reporter assay, antisense RNA loss-of-function Mechanisms of development Medium 11025204
2001 Loss of ELF3 (ERT) expression in gastric cancer cell lines with undetectable TGF-β RII mRNA is linked to inactivation of a sequence-specific DNA binding protein (nuclear protein complex) that recognizes the ERT promoter element ESE (-186 to -177), suggesting that loss of this transcriptional activator contributes to silencing of ERT and subsequent TGF-β resistance. Promoter cloning, EMSA, transient transfection, deletion analysis Oncogene Medium 11313868
2003 Induction of ELF3 (ESE-1) gene expression by IL-1β in synovial fibroblasts, chondrocytes, osteoblasts, and monocytes requires activation of NF-κB and binding of p50 and p65 NF-κB family members to a high-affinity NF-κB binding site in the ESE-1 promoter. Overexpression of IκB using adenoviral vector blocked IL-1β-induced ESE-1 mRNA expression. ChIP confirmed NF-κB binds the ESE-1 promoter in vivo. Luciferase reporter assay with promoter mutants, EMSA with supershift assay, adenoviral IκB overexpression, chromatin immunoprecipitation (ChIP) Arthritis and rheumatism High 12746898
2003 ELF3 (ESE-1/Ese-1) cooperates functionally with the Skn-1a isoform of Oct-11 to drive SPRR2A expression in keratinocyte terminal differentiation. This cooperativity depends on an N-terminal pointed-like domain in Skn-1a; the Skn-1d1 isoform counteracts this cooperativity. Identifies ELF3 as part of a multi-factor complex regulating keratinocyte differentiation. Transient co-transfection reporter assays, domain deletion analysis The Journal of biological chemistry Medium 12624109
2004 ELF3 (ESE-1) protein is cytoplasmic in human breast cancer cells. Stably expressed GFP-ESE-1 transforms MCF-12A human mammary epithelial cells via a cytoplasmic, non-transcriptional mechanism mediated by the unique 40-amino acid serine/aspartic acid-rich (SAR) domain. Nuclear localization of ESE-1 induces apoptosis via a transcription-dependent mechanism. Fusion of an NLS to ESE-1 or SAR domain inhibits transforming capacity. Stable transfection, GFP subcellular localization, NLS/NES fusion constructs, apoptosis assays, domain deletion analysis Molecular and cellular biology High 15169914
2004 ELF3 (ESE-1) is a novel transcriptional mediator of angiopoietin-1 (Ang-1) expression in the setting of inflammation. ESE-1 binds to specific ETS sites within the Ang-1 promoter that are required for transactivation; mutation of a high-affinity ESE-1 binding site markedly reduces Ang-1 transactivation and cytokine inducibility. Transcriptional profiling confirmed direct induction of endogenous Ang-1 by ESE-1. Transient transfection reporter assay, site-directed mutagenesis of promoter, EMSA, transcriptional profiling The Journal of biological chemistry High 14715662
2005 ELF3 (ESE-1) binds to multiple ETS sites on the COX-2 promoter and activates COX-2 expression in response to LPS and pro-inflammatory cytokines in monocytes/macrophages. Mutation of ETS sites in the COX-2 promoter or overexpression of dominant-negative ESE-1 inhibits LPS-mediated COX-2 induction. ESE-1's effect is enhanced by cooperation with NF-κB and NFAT. Luciferase reporter assay, promoter mutagenesis, EMSA, dominant-negative overexpression, co-transfection The FEBS journal High 15794755
2008 ELF3 (ESE-1) expression in airway epithelial cells is upregulated by IL-1β and TNF-α via NF-κB activation. ESE-1 also upregulates ESE-3 expression and downregulates its own induction by cytokines (negative autoregulation). In Elf3 knockout mice, IL-6 expression is downregulated following inflammatory stimulation. NF-κB promoter analysis, transfection, siRNA, Elf3 knockout mouse Cell research High 18475289
2008 ELF3 (ESE-1) is a potent transcriptional repressor of the type II collagen gene (COL2A1) in chondrocytes in response to IL-1β, via NF-κB-dependent binding to tandem ETS sites at -403/-381 bp in the COL2A1 promoter. ChIP confirmed IL-1β-induced ESE-1 binding to the COL2A1 promoter in vivo. ETS-1, by contrast, activates COL2A1 and blocks IL-1β inhibition. Transient co-transfection, siRNA, ChIP, EMSA, promoter deletion analysis Journal of cellular physiology High 18044710
2008 ELF3 (ESE-1) mediates tolfenamic acid-induced EGR-1 expression and apoptosis in colorectal cancer cells. ESE-1 binds to an ETS binding site at -400/-394 bp in the EGR-1 promoter (confirmed by EMSA and ChIP), and tolfenamic acid promotes nuclear translocation of ESE-1. Silencing ESE-1 attenuates tolfenamic acid-induced EGR-1 expression and apoptosis. EMSA, ChIP, luciferase reporter assay, siRNA knockdown, nuclear translocation assay Molecular cancer therapeutics High 19074849
2008 ELF3 (ESE-1) suppresses invasion of oral squamous cell carcinoma cells by transcriptionally repressing MMP-9 via an ETS binding site in the MMP-9 promoter. ESE-1 transfection reduces invasion activity and 92 kDa gelatinolytic activity, and luciferase/mutation analysis confirmed that the ETS binding site in the MMP-9 promoter mediates this suppression. Transfection, invasion assay, gelatin zymography, Northern blot, luciferase assay, mutation analysis Oral diseases Medium 18302674
2010 ELF3 (ESE-1) plays a counter-regulatory role in angiotensin II (Ang II)-mediated vascular inflammation and remodeling. ESE-1 KO mice show exaggerated intimal medial thickness, perivascular fibrosis, T cell and macrophage infiltration, greater PCNA staining, blunted NOS2 (iNOS) induction, and an exaggerated systolic blood pressure response to Ang II compared to wild-type controls. ESE-1 knockout mice, Ang II infusion model, histology, immunostaining American journal of hypertension Medium 20689519
2011 Elf3 regulates allergic airway inflammation by controlling dendritic cell (DC)-driven T cell differentiation. Elf3−/− mice show impaired IL-6 and IL-12 production by DCs, impaired Th1 and Th17 differentiation, and exaggerated Th2 responses with increased IgE. The impairment of IL-12 production was attributed to impaired IL-12p40 gene induction in Elf3-deficient DCs. Elf3 knockout mice, OVA sensitization/challenge models, ELISA, flow cytometry Journal of immunology High 21948981
2011 ESE-1 (ELF3) SAR domain-mediated mammary cell transformation occurs exclusively in the cytoplasm. NLS mapped to six basic amino acids (242HGKRRR247) in the AT-hook domain. Two CRM1-dependent NES motifs were identified: NES1 in the pointed domain (102LCNCALEELRL112) and NES2 in the DNA binding domain (275LWEFIRDILI284). Site-specific mutation of NES2 abrogates transforming activity. The SAR domain is accessible for protein-protein interactions. GFP reporter subcellular localization, site-directed mutagenesis, NLS/NES fusion constructs, transformation assay Molecular cancer High 21871131
2013 ELF3 is a repressor of androgen receptor (AR) transcriptional activity in prostate cancer cells. ELF3 physically interacts with AR (biochemical pulldown), and this interaction inhibits recruitment of AR to androgen response elements within target gene promoters. ELF3 knockdown increases AR transcriptional activity and promotes cell migration; ELF3 overexpression inhibits tumor growth in vitro and in xenograft models. Reporter-based transfection assays, endogenous AR target gene qPCR, siRNA knockdown, co-immunoprecipitation/pulldown, ChIP, xenograft mouse model Oncogene High 23435425
2016 RIPK4 is upstream of ELF3 in keratinocytes: RIPK4 is required for PMA-inducible ELF3 gene expression. RIPK4 acts via phosphorylation and activation of IRF6, and IRF6 in turn regulates ELF3 expression. GRHL3, a downstream target of IRF6, also contributes to ELF3 regulation. ELF3 in this pathway regulates SPRR1A, SPRR1B, and TGM1 expression during keratinocyte cornification. siRNA knockdown of RIPK4, IRF6, GRHL3; qRT-PCR; Western blot Cellular signalling Medium 27667567
2018 ELF3 promotes EMT in hepatocellular carcinoma by transcriptionally repressing miR-141-3p, thereby de-repressing ZEB1. ChIP assays showed ELF3 binds the miR-141-3p promoter to suppress its transcription. ELF3 knockdown reverses EMT via miR-141-3p upregulation and ZEB1 repression. Gain/loss-of-function studies, ChIP assay, Western blot, migration/invasion assays Cell death & disease Medium 29523781
2018 ELF3 is a negative regulator of EMT transcription factor ZEB1 through its function as an antagonist of Wnt and RAS oncogenic signaling in colorectal cancer cells. ELF3 expression is reduced in response to oncogenic signaling (mutant β-catenin, inducible mutant RAS) and is anti-correlated with ZEB1 and EMT markers. RNA-Seq, siRNA, Western blot, analysis of colorectal cancer TCGA datasets, tumor/normal protein localization Cancer biology & therapy Medium 30148686
2019 ELF3 is amplified at chromosome 1q32.1 in lung adenocarcinoma (LUAD), and ELF3 expression is required for tumor growth. Gene dosage and promoter hypomethylation affect the locus in up to 80% of LUAD analyzed. Pan-cancer network analysis supports subtype and tissue specificity of ELF3's oncogenic role in LUAD. Genomic analysis, functional KD in LUAD cells, pan-cancer expression network analysis Nature communications Medium 31780666
2021 ELF3 is required for high-level HLA-C expression on extravillous trophoblasts (EVTs). ELF3 and MED1 bind to the proximal HLA-C promoter region (confirmed by ChIP-PCR). ELF3 creates an autoregulatory positive feedback loop by binding its own promoter. The ELF3 gene is regulated by a superenhancer spanning >5 Mb (identified by ATAC-seq and JQ1 sensitivity). The small molecule wrenchnolol blocks ELF3-MED23 interaction, disrupting the feedback loop and downregulating HLA-C. ChIP-PCR, siRNA knockdown, ATAC-seq, wrenchnolol treatment, single-cell RNA-seq Proceedings of the National Academy of Sciences of the United States of America High 33622787
2021 ELF3 is transcriptionally identified as a direct repressor of lncRNA UBE2CP3 in gastric cancer. ELF3 downregulation (via SNAI2 repression of ELF3) leads to UBE2CP3 upregulation, which promotes cancer progression via a miR-138-5p/ITGA2 ceRNA axis. ChIP, luciferase reporter assay, transcriptome sequencing, rescue experiments Oncogene Medium 34274947
2022 In esophageal squamous cell carcinoma, ELF3 promotes EMT by binding to the miR-144 promoter to suppress miR-144-3p transcription, thereby de-repressing ZEB1 and ZEB2. The lncRNA LINC00886, acting via SIRT7-mediated H3K18 deacetylation at the ELF3 promoter, suppresses ELF3 expression, placing SIRT7 as an upstream epigenetic writer controlling ELF3. ChIP (for ELF3 binding to miR-144 promoter and SIRT7/H3K18ac at ELF3 promoter), luciferase reporter, siRNA, Western blot Clinical & experimental metastasis Medium 35616822
2022 ELF3 functions as a transcription factor for IGF1 in epithelial ovarian cancer under hypoxia. ELF3-mediated increase in IGF1 and VEGF secretion promotes endothelial cell proliferation, migration, and tumor angiogenesis. ELF3 silencing under hypoxia significantly attenuated angiogenic activity and tumorigenesis in ex vivo and xenograft models. siRNA knockdown, IGF1/VEGF ELISA, endothelial cell proliferation/migration assays, ex vivo and xenograft models EMBO reports Medium 35695065
2022 ELF3 deficiency in zebrafish disrupts extracellular matrix (ECM) organization and tissue morphogenesis. Elf3 knockdown (morpholino and CRISPR/Cas9) produces short, bent larvae with notochord, craniofacial cartilage, fin, and neural defects, with disorganized ECM in fin and notochord, and dysregulation of genes encoding ECM proteins and matrix metalloproteinases (MMPs). Morpholino antisense knockdown, CRISPR/Cas9 knockdown, in situ hybridization, histology, gene expression analysis PloS one Medium 36383615
2023 ELF3 is required for proinflammatory mediator induction by the synergistic action of IL-17A and TNF in synovial fibroblasts. ELF3 expression is induced by the NF-κB co-factor IκBζ (synthesized in response to IL-17A+TNF), and requires NF-κB signaling and C/EBPβ. siRNA depletion of ELF3 attenuates cytokine and MMP induction. Overexpression of ELF3 or IκBζ synergizes with TNF to upregulate CCL8, and ELF3 depletion abrogates CCL8 induction by IκBζ+TNF. siRNA knockdown, transient overexpression, signaling inhibitors, qRT-PCR, HEK293 and primary synovial fibroblast experiments Rheumatology (Oxford, England) Medium 35792833
2023 ELF3 suppresses gallbladder cancer development by directly repressing epiregulin (EREG) transcription, thereby reducing EGFR/mTORC1 signaling. In vivo (KPCE mouse model), loss of Elf3 leads to upregulation of Ereg and EGFR/mTORC1. ChIP of Elf3-overexpressing organoids confirmed direct ELF3 binding to the Ereg locus. CRISPR deletion of Ereg in KPCE organoids normalized EGFR/mTORC1 activity. Autochthonous mouse model (KPCE), organoids, RNA-seq, ChIP, CRISPR/Cas9 deletion, Western blot, allograft models The Journal of pathology High 37345534
2023 ELF3 is an oncogenic transcription factor in ASCL1-positive neuroendocrine carcinoma (NEC), regulated by a super-enhancer. Combining CUT&Tag (H3K27ac) and ELF3 knockdown RNA-seq defined the ELF3 transcriptional network, including downstream targets AURKA, CDC25B, CLDN4, ITGB6, and YWHAB. ELF3 depletion leads to poor NEC cell viability. ATAC-seq, CUT&Tag (H3K27ac), ELF3 siRNA knockdown + RNA-seq, loss-of-function cell viability assay Cancer science Medium 36840413
2023 Retinoic acid signaling (RAR/RXR) and Elf3 upregulate Netrin-1 in disseminated pancreatic ductal adenocarcinoma tumor cells as part of a feedforward metastatic niche mechanism involving hepatic stellate cell activation and retinoic acid secretion. In vitro and in vivo metastasis models, gene expression analysis, pathway inhibition Cell reports Low 37922311
2024 ELF3 directly binds to the SLC31A1 (copper transporter) promoter and transcriptionally activates it, as demonstrated by luciferase reporter assay and ChIP. ELF3 is upregulated in cisplatin-induced acute kidney injury and positively correlates with SLC31A1 expression; ELF3-driven SLC31A1 induction increases copper uptake, causing mitochondrial dysfunction and cuproptosis. Luciferase reporter assay, ChIP, siRNA knockdown, Western blot, in vivo mouse AKI model Chemico-biological interactions Medium 38462020
2024 WTAP-mediated N6-methyladenosine (m6A) modification of ELF3 mRNA promotes ELF3 expression in an m6A-dependent manner in human dermal fibroblasts. ELF3 overexpression induces cellular senescence; ELF3 directly binds the IRF8 promoter at the -817 to -804 site to induce IRF8-mediated SASP (senescence-associated secretory phenotype). shWTAP suppresses fibroblast senescence, which is reversed by exogenous ELF3 overexpression. Proteomics, m6A sequencing, ChIP (ELF3 binding to IRF8 promoter), siRNA/shRNA, overexpression, in vivo skin aging model International journal of biological sciences Medium 38481803
2014 ESE-1 (ELF3) upregulates GP73 expression in hepatocellular carcinoma cells by directly binding to the GP73 promoter, as demonstrated by ChIP. Both ESE-1 and GP73 are co-induced by IL-1β in vitro and in liver inflammation in vivo. ChIP, overexpression, siRNA knockdown, qRT-PCR, in vivo liver inflammation model Cell & bioscience Medium 25530841

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 COP1 and ELF3 control circadian function and photoperiodic flowering by regulating GI stability. Molecular cell 325 19061637
2016 ESX secretion systems: mycobacterial evolution to counter host immunity. Nature reviews. Microbiology 302 27665717
1997 Isolation and characterization of a novel epithelium-specific transcription factor, ESE-1, a member of the ets family. Molecular and cellular biology 200 9234700
2009 ESX/type VII secretion systems and their role in host-pathogen interaction. Current opinion in microbiology 193 19155186
2017 Mycobacterial ESX-1 secretion system mediates host cell lysis through bacterium contact-dependent gross membrane disruptions. Proceedings of the National Academy of Sciences of the United States of America 190 28119503
2008 ESX-1-dependent cytolysis in lysosome secretion and inflammasome activation during mycobacterial infection. Cellular microbiology 163 18503637
2011 Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation. Journal of immunology (Baltimore, Md. : 1950) 119 21957139
1998 A novel ets-related transcription factor, ERT/ESX/ESE-1, regulates expression of the transforming growth factor-beta type II receptor. The Journal of biological chemistry 103 9417054
2007 A unique Mycobacterium ESX-1 protein co-secretes with CFP-10/ESAT-6 and is necessary for inhibiting phagosome maturation. Molecular microbiology 102 17908204
2018 ELF3, ELF5, EHF and SPDEF Transcription Factors in Tissue Homeostasis and Cancer. Molecules (Basel, Switzerland) 99 30200227
2018 ELF3 promotes epithelial-mesenchymal transition by protecting ZEB1 from miR-141-3p-mediated silencing in hepatocellular carcinoma. Cell death & disease 94 29523781
2014 Natural course of Fabry disease and the effectiveness of enzyme replacement therapy: a systematic review and meta-analysis: effectiveness of ERT in different disease stages. Journal of inherited metabolic disease 91 24492980
1999 Characterization of ESE-2, a novel ESE-1-related Ets transcription factor that is restricted to glandular epithelium and differentiated keratinocytes. The Journal of biological chemistry 91 10506207
2003 Responses to the proinflammatory cytokines interleukin-1 and tumor necrosis factor alpha in cells derived from rheumatoid synovium and other joint tissues involve nuclear factor kappaB-mediated induction of the Ets transcription factor ESE-1. Arthritis and rheumatism 85 12746898
2017 ELF3 is a negative regulator of epithelial-mesenchymal transition in ovarian cancer cells. Oncotarget 80 28199976
2014 Mycobacterial Esx-3 requires multiple components for iron acquisition. mBio 76 24803520
2011 Multiple roles of the epithelium-specific ETS transcription factor, ESE-1, in development and disease. Laboratory investigation; a journal of technical methods and pathology 72 22157719
2019 The Mycobacterium marinum ESX-1 system mediates phagosomal permeabilization and type I interferon production via separable mechanisms. Proceedings of the National Academy of Sciences of the United States of America 70 31879349
2021 Bone marrow mesenchymal stem cell-derived exosomal miR-206 promotes osteoblast proliferation and differentiation in osteoarthritis by reducing Elf3. Journal of cellular and molecular medicine 66 34160894
2019 Impaired autophagic and mitochondrial functions are partially restored by ERT in Gaucher and Fabry diseases. PloS one 65 30633777
2018 MiR-320a-3p/ELF3 axis regulates cell metastasis and invasion in non-small cell lung cancer via PI3K/Akt pathway. Gene 60 29803922
2012 Infantile Pompe disease on ERT: update on clinical presentation, musculoskeletal management, and exercise considerations. American journal of medical genetics. Part C, Seminars in medical genetics 60 22252989
2008 Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells: potential roles in airway inflammation. Cell research 59 18475289
2021 The ELF3-regulated lncRNA UBE2CP3 is over-stabilized by RNA-RNA interactions and drives gastric cancer metastasis via miR-138-5p/ITGA2 axis. Oncogene 58 34274947
2008 ESE-1/EGR-1 pathway plays a role in tolfenamic acid-induced apoptosis in colorectal cancer cells. Molecular cancer therapeutics 58 19074849
2004 ESE-1 is a novel transcriptional mediator of angiopoietin-1 expression in the setting of inflammation. The Journal of biological chemistry 54 14715662
2019 Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma. Nature communications 52 31780666
2005 The Ets transcription factor ESE-1 mediates induction of the COX-2 gene by LPS in monocytes. The FEBS journal 51 15794755
2004 The ETS transcription factor ESE-1 transforms MCF-12A human mammary epithelial cells via a novel cytoplasmic mechanism. Molecular and cellular biology 49 15169914
2000 Over-expression of ERT(ESX/ESE-1/ELF3), an ets-related transcription factor, induces endogenous TGF-beta type II receptor expression and restores the TGF-beta signaling pathway in Hs578t human breast cancer cells. Oncogene 47 10644990
2022 LncRNA ELF3-AS1 inhibits gastric cancer by forming a negative feedback loop with SNAI2 and regulates ELF3 mRNA stability via interacting with ILF2/ILF3 complex. Journal of experimental & clinical cancer research : CR 46 36457025
2008 ESE-1 is a potent repressor of type II collagen gene (COL2A1) transcription in human chondrocytes. Journal of cellular physiology 46 18044710
2016 Modular Organization of the ESX-5 Secretion System in Mycobacterium tuberculosis. Frontiers in cellular and infection microbiology 45 27200304
2000 Ets family transcription factor ESE-1 is expressed in corneal epithelial cells and is involved in their differentiation. Mechanisms of development 43 11025204
2019 ESX/Type VII Secretion Systems-An Important Way Out for Mycobacterial Proteins. Microbiology spectrum 41 31298207
2022 Proteo-genetic analysis reveals clear hierarchy of ESX-1 secretion in Mycobacterium marinum. Proceedings of the National Academy of Sciences of the United States of America 39 35671426
2011 Developmental validation of the PowerPlex® ESX 16 and PowerPlex® ESX 17 Systems. Forensic science international. Genetics 38 21466982
2014 A novel ESX-1 locus reveals that surface-associated ESX-1 substrates mediate virulence in Mycobacterium marinum. Journal of bacteriology 37 24610712
2013 ESX-1-induced apoptosis during mycobacterial infection: to be or not to be, that is the question. Frontiers in cellular and infection microbiology 37 24364000
2022 Hypoxia-induced ELF3 promotes tumor angiogenesis through IGF1/IGF1R. EMBO reports 35 35695065
2021 Pore-forming Esx proteins mediate toxin secretion by Mycobacterium tuberculosis. Nature communications 35 33452244
1999 Genomic organization of the human ELF3 (ESE-1/ESX) gene, a member of the Ets transcription factor family, and identification of a functional promoter. Genomics 33 10049594
2020 Modeling Tubercular ESX-1 Secretion Using Mycobacterium marinum. Microbiology and molecular biology reviews : MMBR 32 32878966
2020 ESX secretion system: The gatekeepers of mycobacterial survivability and pathogenesis. European journal of microbiology & immunology 32 33174865
2017 Esx Systems and the Mycobacterial Cell Envelope: What's the Connection? Journal of bacteriology 32 28461452
2003 Distinct functional interactions of human Skn-1 isoforms with Ese-1 during keratinocyte terminal differentiation. The Journal of biological chemistry 31 12624109
2023 The ELF3 transcription factor is associated with an epithelial phenotype and represses epithelial-mesenchymal transition. Journal of biological engineering 30 36864480
2021 Mycobacterium tuberculosis ESX-1-secreted substrate protein EspC promotes mycobacterial survival through endoplasmic reticulum stress-mediated apoptosis. Emerging microbes & infections 30 33290182
2019 A New ESX-1 Substrate in Mycobacterium marinum That Is Required for Hemolysis but Not Host Cell Lysis. Journal of bacteriology 30 30833360
2024 The copper transporter, SLC31A1, transcriptionally activated by ELF3, imbalances copper homeostasis to exacerbate cisplatin-induced acute kidney injury through mitochondrial dysfunction. Chemico-biological interactions 29 38462020
2023 Netrin-1 feedforward mechanism promotes pancreatic cancer liver metastasis via hepatic stellate cell activation, retinoid, and ELF3 signaling. Cell reports 28 37922311
2020 Modification of a PE/PPE substrate pair reroutes an Esx substrate pair from the mycobacterial ESX-1 type VII secretion system to the ESX-5 system. The Journal of biological chemistry 28 32184351
2016 Discovery of the type VII ESX-1 secretion needle? Molecular microbiology 28 27859892
2023 IL-17A and TNF synergistically drive expression of proinflammatory mediators in synovial fibroblasts via IκBζ-dependent induction of ELF3. Rheumatology (Oxford, England) 25 35792833
2019 Fabry's disease and stroke: Effectiveness of enzyme replacement therapy (ERT) in stroke prevention, a review with meta-analysis. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 25 30955952
2019 Integrated transcriptomic and proteomic analysis of pathogenic mycobacteria and their esx-1 mutants reveal secretion-dependent regulation of ESX-1 substrates and WhiB6 as a transcriptional regulator. PloS one 24 30673778
2013 ELF3 is a repressor of androgen receptor action in prostate cancer cells. Oncogene 24 23435425
2022 Downregulation of LINC00886 facilitates epithelial-mesenchymal transition through SIRT7/ELF3/miR-144 pathway in esophageal squamous cell carcinoma. Clinical & experimental metastasis 23 35616822
2018 Direct cell-cell contact activates SigM to express the ESX-4 secretion system in Mycobacterium smegmatis. Proceedings of the National Academy of Sciences of the United States of America 23 29941598
2008 ESE-1 inhibits the invasion of oral squamous cell carcinoma in conjunction with MMP-9 suppression. Oral diseases 23 18302674
2019 LncRNA ELF3-AS1 is involved in the regulation of oral squamous cell carcinoma cell proliferation by reprogramming glucose metabolism. OncoTargets and therapy 22 31686842
2018 Structural Variability of EspG Chaperones from Mycobacterial ESX-1, ESX-3, and ESX-5 Type VII Secretion Systems. Journal of molecular biology 22 30419243
2015 Gibberellin driven growth in elf3 mutants requires PIF4 and PIF5. Plant signaling & behavior 22 25738547
2011 Elf3 regulates allergic airway inflammation by controlling dendritic cell-driven T cell differentiation. Journal of immunology (Baltimore, Md. : 1950) 22 21948981
2024 A pair of E3 ubiquitin ligases control immunity and flowering by targeting different ELF3 proteins in rice. Developmental cell 21 39025063
2020 The ESX-1 Virulence Factors Downregulate miR-147-3p in Mycobacterium marinum-Infected Macrophages. Infection and immunity 21 32253249
2014 Immune responses and hypercoagulation in ERT for Pompe disease are mutation and rhGAA dose dependent. PloS one 21 24897114
2024 The function of the ELF3 gene and its mechanism in cancers. Life sciences 20 38614305
2021 ELF3 activated by a superenhancer and an autoregulatory feedback loop is required for high-level HLA-C expression on extravillous trophoblasts. Proceedings of the National Academy of Sciences of the United States of America 20 33622787
2021 Crosstalk between the ancestral type VII secretion system ESX-4 and other T7SS in Mycobacterium marinum. iScience 20 35005535
2018 Esx Paralogs Are Functionally Equivalent to ESX-1 Proteins but Are Dispensable for Virulence in Mycobacterium marinum. Journal of bacteriology 20 29555701
2018 ELF3 is an antagonist of oncogenic-signalling-induced expression of EMT-TF ZEB1. Cancer biology & therapy 20 30148686
2022 The ESX-1 Substrate PPE68 Has a Key Function in ESX-1-Mediated Secretion in Mycobacterium marinum. mBio 19 36409073
2011 Mapping of ESE-1 subdomains required to initiate mammary epithelial cell transformation via a cytoplasmic mechanism. Molecular cancer 19 21871131
2022 Fabry Disease and the Effectiveness of Enzyme Replacement Therapy (ERT) in Left Ventricular Hypertrophy (LVH) Improvement: A Review and Meta-Analysis. International journal of medical sciences 18 34975306
2024 WTAP Mediated N6-methyladenosine RNA Modification of ELF3 Drives Cellular Senescence by Upregulating IRF8. International journal of biological sciences 17 38481803
2021 Priming mycobacterial ESX-secreted protein B to form a channel-like structure. Current research in structural biology 17 34337436
2001 Sequence-specific enhancer binding protein is responsible for the differential expression of ERT/ESX/ELF-3/ESE-1/jen gene in human gastric cancer cell lines: Implication for the loss of TGF-beta type II receptor expression. Oncogene 17 11313868
2023 An integrative epigenomic approach identifies ELF3 as an oncogenic regulator in ASCL1-positive neuroendocrine carcinoma. Cancer science 16 36840413
2023 High Bacillary Burden and the ESX-1 Type VII Secretion System Promote MHC Class I Presentation by Mycobacterium tuberculosis-Infected Macrophages to CD8 T Cells. Journal of immunology (Baltimore, Md. : 1950) 16 37000471
2021 ESX-1-Independent Horizontal Gene Transfer by Mycobacterium tuberculosis Complex Strains. mBio 16 34006663
2016 A novel regulatory relationship between RIPK4 and ELF3 in keratinocytes. Cellular signalling 16 27667567
2014 Epithelium-Specific ETS (ESE)-1 upregulated GP73 expression in hepatocellular carcinoma cells. Cell & bioscience 16 25530841
2023 Virus-like nanoparticles as enzyme carriers for Enzyme Replacement Therapy (ERT). Virology 15 36791560
2022 The ESX-4 substrates, EsxU and EsxT, modulate Mycobacterium abscessus fitness. PLoS pathogens 14 35960766
2010 The counter-regulatory effects of ESE-1 during angiotensin II-mediated vascular inflammation and remodeling. American journal of hypertension 13 20689519
2002 The role of ERT/HRT. Best practice & research. Clinical obstetrics & gynaecology 13 12099668
2023 ELF3 suppresses gallbladder cancer development through downregulation of the EREG/EGFR/mTOR complex 1 signalling pathway. The Journal of pathology 12 37345534
2023 ESX-3 secretion system in Mycobacterium: An overview. Biochimie 12 37879428
2025 Single-cell analysis reveals Mycobacterium tuberculosis ESX-1-mediated accumulation of permissive macrophages in infected mouse lungs. Science advances 11 39813329
2025 Frequently arising ESX-1-associated phase variants influence Mycobacterium tuberculosis fitness in the presence of host and antibiotic pressures. mBio 11 39873486
2016 A metabolomics investigation of the function of the ESX-1 gene cluster in mycobacteria. Microbial pathogenesis 11 27744102
2004 Partially unspliced and fully spliced ELF3 mRNA, including a new Alu element in human breast cancer. Breast cancer research and treatment 11 14997048
2023 Dysregulation of Mycobacterium marinum ESX-5 Secretion by Novel 1,2,4-oxadiazoles. Biomolecules 10 36830581
2022 IMB-BZ as an Inhibitor Targeting ESX-1 Secretion System to Control Mycobacterial Infection. The Journal of infectious diseases 10 34558604
2020 Polarly Localized EccE1 Is Required for ESX-1 Function and Stabilization of ESX-1 Membrane Proteins in Mycobacterium tuberculosis. Journal of bacteriology 10 31843799
2025 Deletion of ESX-3 and ESX-4 secretion systems in Mycobacterium abscessus results in highly impaired pathogenicity. Communications biology 9 39900631
2023 Intragranuloma Accumulation and Inflammatory Differentiation of Neutrophils Underlie Mycobacterial ESX-1-Dependent Immunopathology. mBio 9 37017530
2022 LINC00472 suppresses oral squamous cell carcinoma growth by targeting miR-455-3p/ELF3 axis. Bioengineered 9 35258410
2022 Elf3 deficiency during zebrafish development alters extracellular matrix organization and disrupts tissue morphogenesis. PloS one 9 36383615

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