Affinage

ERG

Transcriptional regulator ERG · UniProt P11308

Length
479 aa
Mass
53.8 kDa
Annotated
2026-04-28
100 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ERG is an ETS family transcription factor that functions as a master regulator of endothelial cell identity, hematopoietic stem cell differentiation, and tissue homeostasis, while acting as a potent oncogene when dysregulated. ERG binds ETS motifs genome-wide and recruits chromatin remodeling (BAF/SWI-SNF) and histone-modifying (p300, KDM4A) complexes to enhancers, directly activating target genes including VE-cadherin, DLL4, SOX9, CXCR4, PIM1, YAP1, EBF1, and PAX5; in endothelial cells, VEGF/ERK-mediated phosphorylation activates ERG to drive angiogenesis and capillary homeostasis, while in prostate epithelium, ERG redirects androgen receptor binding to non-canonical targets and silences basal lineage determinants such as Trp63 through three-dimensional chromatin remodeling (PMID:25, PMID:30078722, PMID:23426182, PMID:32701507, PMID:32541654). ERG protein stability is controlled by SPOP/Cullin3-dependent ubiquitination targeting an N-terminal degron—lost in TMPRSS2-ERG fusion products—and by TRIM25-mediated ubiquitination counterbalanced by USP9X deubiquitination (PMID:26344095, PMID:26344096, PMID:27626314). ERG is oncogenically activated through chromosomal fusions (TMPRSS2-ERG in prostate cancer, EWS-ERG and FUS-ERG in Ewing sarcoma), transcriptional upregulation by EVI1 in AML, and expression of a dominant-negative ERGalt isoform driven by DUX4 in B-ALL, and its overexpression is sufficient to transform fibroblasts and initiate prostate neoplasia in transgenic mice (PMID:7731694, PMID:18245377, PMID:8076344, PMID:36095844, PMID:27776115).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1987 High

    Establishing ERG as a distinct ETS family member resolved its identity as a transcription factor with conserved DNA-binding and pointed domains, providing the foundation for all subsequent functional studies.

    Evidence cDNA cloning and sequence analysis revealing a 363-residue protein with ETS domain homology

    PMID:3476934

    Open questions at the time
    • No target genes identified
    • No functional assay performed
    • Expression pattern unknown
  2. 1994 High

    Discovery of the EWS-ERG fusion in Ewing sarcoma established ERG as a recurrent translocation partner in human cancer, raising the question of whether ERG possesses intrinsic oncogenic activity.

    Evidence RT-PCR and cytogenetic analysis of Ewing sarcoma cell line identifying EWS-ERG fusion transcript

    PMID:8076344

    Open questions at the time
    • Transforming activity of the fusion not directly tested
    • Mechanism of oncogenic activation unknown
  3. 1995 High

    Demonstrating that ERG overexpression alone transforms NIH3T3 cells confirmed ERG as a bona fide proto-oncogene, establishing that its oncogenic potential does not require a fusion partner.

    Evidence Stable ERG2 transfection with soft agar colony formation and nude mouse tumor growth

    PMID:7731694

    Open questions at the time
    • Downstream transcriptional targets mediating transformation not identified
    • Relevance to human epithelial cancers not shown
  4. 2001 High

    Identification of endothelial-restricted ERG isoforms and mapping of the ETS domain's dual role in DNA binding and Jun/Fos interaction established ERG as a key endothelial transcription factor that integrates AP-1 signaling.

    Evidence RT-PCR/Northern blot profiling across human cell types; ETS domain mutagenesis with binding and transcriptional assays

    PMID:11278640 PMID:11312105

    Open questions at the time
    • Endothelial target genes not identified
    • In vivo endothelial requirement not tested
  5. 2005 High

    Showing that ERG drives megakaryocytic differentiation and directly occupies hematopoietic gene promoters (gpIb, gpIIb, SCL enhancer) revealed its role as a lineage-instructive transcription factor in hematopoiesis.

    Evidence Forced expression in K562 cells with differentiation assays; in vivo ChIP at megakaryocytic promoters

    PMID:16140924

    Open questions at the time
    • Loss-of-function in hematopoietic stem cells not performed
    • Functional redundancy with FLI-1 not resolved
  6. 2008 High

    Multiple studies converged to establish ERG as essential for endothelial tube formation, VE-cadherin-mediated survival, angioblast specification, and—when overexpressed in prostate—sufficient to initiate neoplasia, revealing its dual physiological and oncogenic roles.

    Evidence siRNA knockdown with ChIP/rescue for VE-cadherin in HUVECs; zebrafish morpholino epistasis; transgenic ERG-overexpressing mouse prostate model with invasion assays

    PMID:18195090 PMID:18245377 PMID:19027849

    Open questions at the time
    • Endothelial ERG target gene network not mapped genome-wide
    • Cooperating oncogenic events for prostate cancer progression not defined
  7. 2009 High

    Genetic dosage experiments in trisomic mice demonstrated that Erg trisomy is required for myeloproliferation in Down syndrome, establishing ERG gene dosage as a driver of megakaryocyte expansion and linking it to human disease.

    Evidence Reduction of Erg to disomy in Ts65Dn mice correcting megakaryocytosis and progenitor expansion

    PMID:20007548

    Open questions at the time
    • Direct transcriptional targets mediating megakaryocyte expansion not identified
    • Cooperation with GATA1 mutations in transient myeloproliferative disease not fully dissected
  8. 2013 High

    ChIP-seq in TMPRSS2-ERG fusion-positive prostate cancer cells revealed that ERG redirects androgen receptor to non-canonical enhancers including a cryptic SOX9 enhancer, establishing the mechanistic basis for ERG's oncogenic transcriptional reprogramming.

    Evidence Integrated ERG/AR ChIP-seq in VCaP cells; SOX9 knockdown phenocopying ERG loss in invasion and tumor growth

    PMID:23426182

    Open questions at the time
    • Structural basis of ERG-AR interaction unknown
    • Whether AR redirection is sufficient without additional cofactors not tested
  9. 2015 High

    Two independent groups simultaneously discovered that SPOP/Cullin3 ubiquitinates ERG via an N-terminal degron that is absent in TMPRSS2-ERG fusion products, explaining why fusion-derived ERG escapes proteasomal degradation in prostate cancer.

    Evidence In vitro ubiquitination reconstitution; degron mutagenesis; proteasomal degradation assays with SPOP wild-type and cancer mutants

    PMID:26344095 PMID:26344096

    Open questions at the time
    • In vivo therapeutic restoration of ERG degradation not demonstrated
    • Quantitative contribution of SPOP versus TRIM25 pathways unclear
  10. 2015 High

    Conditional ERG knockout in mouse joints revealed a physiological requirement for ERG in articular cartilage homeostasis through direct transcriptional activation of PTHrP and lubricin, extending ERG's known roles beyond endothelium and blood.

    Evidence Gdf5-Cre conditional knockout with progressive osteoarthritis phenotype; promoter-reporter assays with ETS site mutations

    PMID:26097038

    Open questions at the time
    • Whether ERG loss contributes to human osteoarthritis not established
    • Upstream signals regulating ERG in chondrocytes unknown
  11. 2016 High

    Identification of TRIM25 as an additional E3 ligase for ERG and USP9X as a counteracting deubiquitinase, together with the discovery that ERG upregulates TRIM25 to create a feedback loop, revealed a multi-layered ubiquitin-dependent control circuit governing ERG protein levels.

    Evidence In vitro ubiquitination with TRIM25; co-IP of USP9X-ERG; TRIM25 knockdown stabilizing ERG protein

    PMID:27626314

    Open questions at the time
    • Relative quantitative contribution of TRIM25 versus SPOP in different cell types not determined
    • Structural basis of USP9X recognition of ERG unknown
  12. 2016 High

    VEGF/ERK-dependent phosphorylation of ERG was shown to recruit p300 to drive DLL4 and angiogenic target gene transcription, while DUX4-driven ERGalt in B-ALL was identified as a dominant-negative isoform, demonstrating how post-translational and isoform-level mechanisms diversify ERG function.

    Evidence ERK inhibition with ERG phosphorylation and p300 ChIP assays; ChIP-seq enhancer mapping in endothelial cells; genomic sequencing and functional assays for DUX4-driven ERGalt

    PMID:27776115 PMID:28536097

    Open questions at the time
    • Identity of kinase(s) phosphorylating specific ERG residues in endothelial cells not fully mapped
    • Structural basis of ERGalt dominant-negative activity not resolved
  13. 2018 High

    Demonstration that ERG physically recruits and retargets BAF chromatin remodeling complexes genome-wide, and that BAF ATPase activity is required for ERG's transcriptional output, established BAF as the principal chromatin effector of ERG-driven gene regulation.

    Evidence Co-IP/pulldown; genome-wide ChIP-seq of ERG and BAF subunits; BAF ATPase inhibition; prostate organoid basal-to-luminal transition assay

    PMID:30078722

    Open questions at the time
    • Whether specific BAF subunit composition dictates ERG-dependent enhancer selection unknown
    • Whether BAF dependence applies to ERG functions in endothelial cells not tested
  14. 2020 High

    ERG was shown to be essential for early B lymphopoiesis by initiating a transcription factor cascade (EBF1, PAX5) required for V(D)J recombination, and separately to silence the basal lineage determinant Trp63 through three-dimensional chromatin loop disruption, revealing ERG as a master regulator of lineage fate in multiple tissues.

    Evidence Conditional Erg KO with RNA-seq/ChIP-seq and Ig gene rescue in B cells; Hi-C/ChIA-PET plus targeted enhancer deletion for Trp63 in prostate

    PMID:32541654 PMID:32701507

    Open questions at the time
    • Whether ERG's 3D chromatin remodeling role extends to hematopoietic loci not examined
    • Redundancy with other ETS factors in B cell development not fully resolved
  15. 2022 High

    Conditional endothelial ERG deletion in adult mouse lungs impaired capillary homeostasis and fibrosis resolution, with transcriptional signatures resembling human lung fibrosis and aging, extending ERG's essential endothelial role from development to adult tissue maintenance.

    Evidence Conditional ERG deletion; scRNA-seq showing gCap loss; ATAC-seq/RNA-seq; bleomycin fibrosis model; in vitro paracrine fibroblast activation assay

    PMID:35879310

    Open questions at the time
    • Whether ERG loss is causal in human pulmonary fibrosis not established
    • Specific ERG target genes mediating anti-fibrotic paracrine signaling not identified
  16. 2023 High

    CRISPR screens and ChIP-seq identified ERG as the critical downstream effector of EVI1 in AML, with EVI1 directly occupying an intragenic ERG enhancer, establishing a new oncogenic axis distinct from chromosomal fusions.

    Evidence CRISPR dependency screens; EVI1 ChIP-seq at ERG enhancer; ERG knockdown inducing differentiation; ERG rescue of EVI1-depleted AML cells

    PMID:36095844

    Open questions at the time
    • Whether pharmacological ERG inhibition is feasible for EVI1-driven AML not tested
    • Full set of ERG target genes in AML context not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • No direct small-molecule inhibitor or structural model of full-length ERG exists; the relative contributions of SPOP, TRIM25, and USP9X to ERG protein homeostasis across different tissues remain unquantified; and whether ERG's BAF-dependent chromatin remodeling mechanism operates in its endothelial and hematopoietic functions has not been tested.
  • No crystal or cryo-EM structure of full-length ERG or ERG-BAF complex
  • Tissue-specific quantitative balance of ERG ubiquitin ligases and deubiquitinases undefined
  • Whether BAF dependence is a universal feature of ERG function across lineages untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 12 GO:0003677 DNA binding 11
Localization
GO:0005634 nucleus 10
Pathway
R-HSA-74160 Gene expression (Transcription) 11 R-HSA-1643685 Disease 7 R-HSA-4839726 Chromatin organization 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2
Partners
BRD4EP300FOXO1JUNKDM4ASPOPTRIM25USP9X
Complex memberships
BAF/SWI-SNF chromatin remodeling complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 ERG was identified as a member of the ETS oncogene family, encoding a 363-residue protein with approximately 40% and 70% homology to two domains of v-ets oncogene, establishing its identity as a distinct ETS transcription factor. cDNA cloning and nucleotide sequence analysis Proceedings of the National Academy of Sciences of the United States of America High 3476934
1994 ERG gene is translocated in Ewing's sarcoma via a chromosomal rearrangement juxtaposing the 5' end of EWS to the 3' end of ERG, generating an EWS/ERG fusion transcript expressed at elevated levels. RT-PCR, cytogenetic and molecular analysis of Ewing's sarcoma cell line Cancer genetics and cytogenetics High 8076344
1995 Overexpression of ERG2 in NIH3T3 cells confers oncogenic transformation, including growth in low serum, colony formation in soft agar, and tumor formation in nude mice, establishing ERG as a proto-oncogene with mitogenic and transforming activity. Stable transfection of ERG2 expression construct into NIH3T3 cells; soft agar colony assay; nude mouse xenograft Oncogene High 7731694
2001 ERG isoforms (Erg-3/p55(Erg) and p38(Erg)) are selectively expressed in endothelial cells among human cell types, indicating isoform-specific roles in regulation of endothelial-restricted gene expression. RT-PCR, Northern blotting, 5'-RACE on primary and established human cell lines The international journal of biochemistry & cell biology Medium 11312105
2001 ERG physically interacts with Jun/Fos heterodimer through its ETS DNA-binding domain; residue R367 is required for both DNA binding and Erg-Jun/Fos complex formation, while Y371 is specifically required for transcriptional synergy with Jun/Fos without abolishing DNA binding. Deletion and point mutagenesis of ERG ETS domain; in vitro binding and transcriptional activation assays; molecular modeling The Journal of biological chemistry High 11278640
2002 ERG1 K+ channel is constitutively tyrosine-phosphorylated and forms a signaling complex with Src tyrosine kinase; Src activation increases ERG current amplitude and shifts voltage dependence, while Src inhibition reduces ERG current. Co-immunoprecipitation; whole-cell patch clamp; Src-selective inhibitory/activating peptides; constitutively active v-Src transfection The Journal of biological chemistry High 11834728
2003 In Ewing's tumors lacking EWS rearrangement, FUS is fused in-frame to ERG, placing the FUS transactivation domain adjacent to the ERG ETS DNA-binding domain, demonstrating interchangeability of TET family transactivation domains with ETS factors in oncogenesis. Sequence-level RT-PCR fusion transcript characterization; BAC FISH on metaphase and interphase nuclei Cancer research High 12907633
2004 Muscarinic receptor stimulation inhibits ERG1 K+ current through a Gq/11-dependent pathway requiring a minimum intracellular Ca2+ level but not a Ca2+ transient, protein kinase C, or tyrosine kinases; recovery is partially dependent on PIP2 resynthesis. Whole-cell patch clamp; co-expression with M1 muscarinic receptors; dominant-negative Gq; constitutively active G-protein constructs; BAPTA Ca2+ chelation; pharmacological inhibitors The Journal of physiology High 15235086
2005 ERG is expressed in hematopoietic stem cells and megakaryoblastic cells; forced ERG expression in K562 erythroleukemia cells induces an erythroid-to-megakaryoblastic phenotypic switch; ERG activates the gpIb megakaryocytic promoter and binds the gpIIb promoter and the SCL/TAL1 hematopoietic enhancer in vivo. Cell line forced expression; megakaryocytic differentiation assays; in vivo ChIP; promoter reporter assays Cancer research High 16140924
2008 ERG is required for endothelial tube formation and cell survival; Erg inhibition reduces VE-cadherin expression; Erg binds directly to the VE-cadherin promoter (by ChIP) and transactivates it; overexpression of VE-cadherin partially rescues apoptosis caused by Erg inhibition; Erg knockdown in a Matrigel plug model decreases vascularization in vivo. Antisense oligonucleotides/siRNA knockdown; ChIP; transactivation assay; VE-cadherin-GFP rescue; in vivo Matrigel plug model Blood High 18195090
2008 Overexpression of ERG in luminal prostate epithelial cells is sufficient to initiate prostate neoplasia (focal PIN) in transgenic mice; ERG overexpression in prostate cell lines increases cell invasion, and ERG protein is expressed in neoplastic human prostate epithelium. Transgenic mouse model with luminal-targeted ERG expression; invasion assays in prostate cell lines; ERG protein detection by Western/IHC Proceedings of the National Academy of Sciences of the United States of America High 18245377
2008 In zebrafish, erg functions downstream of cloche, tal1/scl, and etsrp in the angioblast specification pathway, and plays a redundant but specific role in angioblast specification/proliferation and early angiogenesis, with synergistic interaction with etsrp. Zebrafish morpholino knockdown; gain-of-function injection; in situ hybridization; epistasis analysis with cloche and other pathway genes Mechanisms of development High 19027849
2009 Trisomy of Erg is required for myeloproliferation in a mouse model of Down syndrome (Ts65Dn); functional reduction of Erg to disomy corrects megakaryocytosis and progenitor cell expansion, establishing Erg gene dosage as a key driver of myeloproliferative phenotypes. Loss-of-function allele introduced into trisomic mouse model; hematologic and histopathologic phenotyping Blood High 20007548
2009 ETS2, ERG, and FLI-1 overexpression promotes megakaryocyte expansion and, when combined with Gata1 mutations (knockdown or Gata1s knockin), immortalizes hematopoietic progenitors with JAK/STAT pathway activation. Retroviral overexpression in murine fetal liver progenitors; serial replating assays; flow cytometry; JAK/STAT pathway analysis Blood High 19168790
2010 ERG transcription factor binds directly to the CXCR4 gene promoter and drives androgen-dependent CXCR4 expression in TMPRSS2-ERG fusion-positive prostate cancer cells; ERG knockdown abolishes androgen-induced CXCR4 upregulation and functional CXCR4 signaling. ChIP demonstrating ERG binding to CXCR4 promoter; siRNA-mediated ERG knockdown; androgen stimulation assays; CXCR4 functional assays Translational oncology High 20563261
2011 Forced ERG expression in adult bone marrow cells alters differentiation and promotes T-ALL development (with acquisition of Notch1 mutations) and B cell precursor growth in mouse transplantation models; shRNA-mediated silencing of ERG attenuates growth of human leukemia cell lines, establishing ERG as required for leukemia maintenance. Mouse BM transplantation with ERG-overexpressing cells; shRNA knockdown in human leukemia lines; flow cytometric lineage analysis Blood High 21321361
2011 ERG overexpression in prostate cells induces PIM1 upregulation; ERG directly binds the PIM1 promoter (by ChIP) in RWPE-1 prostate cells; PIM1 upregulation by ERG increases aneuploidy after taxane treatment and alters Cyclin B1 levels. ChIP of ERG at PIM1 promoter; siRNA-mediated ERG silencing; gene expression profiling; flow cytometry for aneuploidy PloS one Medium 22140532
2013 ERG regulates SOX9 expression indirectly by opening a cryptic androgen receptor (AR)-regulated enhancer in the SOX9 gene; ERG redirects AR to non-canonical targets including SOX9, which is a critical downstream effector of ERG-mediated invasion and tumor growth in TMPRSS2-ERG fusion-positive prostate cancer. RNAi knockdown of ERG in VCaP cells; ChIP-seq for AR and ERG; invasion assays; SOX9 knockdown in vivo and in vitro The Journal of clinical investigation High 23426182
2013 miR-145 directly targets the 3' UTR of ERG mRNA; ectopic miR-145 expression reduces ERG protein levels in prostate cancer cells. 3' UTR reporter assay; ectopic miR-145 expression with Western blot for ERG protein The FEBS journal Medium 23480797
2013 ERG governs loss of DNA methylation at the TDRD1 promoter CpG island, leading to TDRD1 transcriptional activation; ERG dosage manipulation by siRNA and forced expression directly controls TDRD1 promoter methylation status in prostate cancer cells. MeDIP-seq; bisulfite sequencing; ERG siRNA knockdown and forced expression; DNMT inhibitor treatment PloS one Medium 23555854
2015 SPOP, a Cullin 3-based E3 ubiquitin ligase substrate adaptor, promotes ubiquitination and proteasomal degradation of wild-type ERG by recognizing a degron motif at the ERG N-terminus; prostate cancer-associated SPOP mutants are deficient in ERG ubiquitination; CKI-mediated phosphorylation of ERG modulates SPOP-ERG interaction; DNA damage drugs (topoisomerase inhibitors) restore the SPOP/ΔERG interaction to promote ΔERG degradation. In vitro ubiquitination assay; co-immunoprecipitation; mutagenesis of ERG degron; proteasome inhibitor assays; pharmacological drug treatment Molecular cell High 26344095
2015 N-terminally truncated ERG proteins encoded by TMPRSS2-ERG fusions lack the N-terminal SPOP degron motif and are resistant to SPOP-mediated proteasomal degradation; prostate cancer-associated SPOP mutations also abrogate ERG degradation. In vitro ubiquitination assay; co-immunoprecipitation; degron mutagenesis; proteasomal degradation assays Molecular cell High 26344096
2015 ERG directly activates the YAP1 promoter through multiple ETS binding sites; ERG binds directly to KDM4A histone demethylase; ERG-KDM4A cooperation reduces H3K27me3 at the YAP1 promoter; YAP1 depletion phenocopies the growth-inhibitory effect of ERG depletion in VCaP prostate cancer cells. Co-IP; promoter reporter assay with ETS site mutagenesis; ChIP for H3K27me3; siRNA knockdown Oncology reports Medium 27109047
2015 ERG conditional knockout in mouse joints leads to progressive osteoarthritis-like cartilage degeneration; ERG directly binds ETS sites in the PTHrP and lubricin gene promoters to stimulate their expression; ERG is required for maintenance of articular cartilage homeostasis postnatally. Conditional knockout (Gdf5-Cre x floxed Erg); surgical OA model; promoter-reporter assays with mutated ETS binding sites; gene expression analysis Arthritis & rheumatology High 26097038
2016 TRIM25 E3 ubiquitin ligase binds and polyubiquitinates full-length and N-terminally truncated ERG variants in vitro; TRIM25 inactivation reduces ERG polyubiquitination and stabilizes ERG protein; ERG upregulates TRIM25 expression, creating a regulatory feedback loop; USP9X deubiquitinase counteracts TRIM25 to stabilize ERG. Co-immunoprecipitation; in vitro ubiquitination assay; TRIM25 knockdown with ERG stability measurement Oncotarget High 27626314
2016 VEGF/ERK signaling induces phosphorylation and activation of ERG in endothelial cells; phospho-ERG recruits the co-activator p300 to drive transcription of DLL4 and a network of VEGF-responsive target genes; ERG ChIP-seq identifies conserved ERG-bound enhancer elements near these target genes including HLX. ERK inhibition; ERG phosphorylation assays; ChIP for ERG and p300; genome-wide gene expression; ChIP-seq; genome editing of ERG-bound HLX enhancer Development (Cambridge, England) High 28536097
2016 The TMPRSS2-ERG encoded truncated ERG (ERGΔ39/T1-E4) binds to bromodomain-1 (BD1) of BRD4; ERG and BRD4 co-occupy a substantial portion of genomic sites; an acetylation-mimicking mutation in ERG enhances the ERG-BRD4 interaction and augments ERG-mediated cell invasion; BET inhibitors partially abrogate this interaction. Co-IP; ChIP-seq meta-analysis; acetylation-mimicking ERG mutant; BET inhibitor treatment; invasion assays Oncotarget Medium 27223260
2016 DUX4 rearrangement in B-ALL drives expression of a novel ERG isoform (ERGalt) via a non-canonical first exon initiated by DUX4 binding; ERGalt retains the DNA-binding and transactivation domains of ERG, functions as a dominant-negative inhibitor of wild-type ERG transcriptional activity, and is transforming. Genomic sequencing; transcriptional assays; dominant-negative functional assays; transformation assays Nature genetics High 27776115
2017 FOXO1 binds directly to ERG and inhibits its transcriptional activity independently of FOXO1's own transcriptional activity; FOXO1 knockdown increases invasion in TMPRSS2-ERG fusion-positive cells in an ERG-dependent manner; combined ERG transgene expression and Foxo1 deletion in mouse prostate produces high-grade PIN, whereas either alone does not. Co-IP of FOXO1 and ERG; FOXO1 knockdown + ERG knockdown epistasis; transgenic mouse model; in vitro invasion assays Cancer research High 28986382
2018 ERG interacts with the mammalian SWI/SNF (BAF) chromatin remodeling complex; ERG drives genome-wide retargeting of BAF complexes in an ETS DNA motif-dependent manner; ERG requires intact BAF complexes for chromatin occupancy and BAF ATPase activity for target gene regulation; BAF complexes are required for ERG-mediated basal-to-luminal transition in prostate organoids. Co-IP/pulldown; ChIP-seq of ERG and BAF subunits; BAF ATPase inhibition; prostate organoid model with BAF depletion Molecular cell High 30078722
2018 ERG directly binds and activates the FZD8 (Frizzled-8) gene promoter in prostate cancer cells; this activation is specific to ERG and not to the related ETS factor ETV1; ERG overexpression induces FZD8 expression, potentially activating Wnt signaling. ChIP demonstrating ERG binding at FZD8 promoter; promoter reporter assay; ERG knockdown; specificity comparison with ETV1 The Prostate Medium 30051493
2020 ERG is essential for early B lymphoid differentiation; ERG initiates a transcriptional network involving EBF1 and PAX5 that promotes expression of V(D)J recombination genes and B cell receptor formation; complementation of Erg deficiency with a rearranged immunoglobulin gene rescues B lineage development. Conditional Erg knockout; RNA-seq/ChIP-seq; rescue with productively rearranged Ig gene; flow cytometric developmental analysis Nature communications High 32541654
2020 ERG inhibits a distal enhancer of Trp63 (a master regulator of prostate basal lineage) by binding it and reducing its chromatin looping activity, thereby silencing Trp63 and promoting luminal differentiation; specific deletion of the ERG-bound Trp63 enhancer removes ERG-mediated inhibition of basal differentiation. 3D chromatin architecture analysis (Hi-C/ChIA-PET); ChIP-seq; ERG KO; AR KO comparison; targeted enhancer deletion The Journal of clinical investigation High 32701507
2021 ERG upregulates wild-type SPOP to dampen androgen receptor (AR) signaling and sustains its own activity through SPOP-mediated degradation of the bromodomain histone reader ZMYND11; conversely, SPOP-mutant tumors stabilize ZMYND11 to repress ERG function, establishing opposing ERG-SPOP regulatory axes. Proteomics; ChIP-seq; co-IP; genetic manipulation of SPOP and ERG in organoid and mouse models; pharmacological SPOP inhibition Nature communications High 33531470
2022 ERG functions as a transcriptional orchestrator of lung capillary homeostasis; loss of endothelial ERG enhances paracrine fibroblast activation in vitro and impairs lung fibrosis resolution in vivo; ERG-deficient mouse lungs show reduced general capillary (gCap) endothelial cell numbers and transcriptional abnormalities resembling aging and human lung fibrosis. Epigenetic/transcriptional analysis (ATAC-seq, RNA-seq); conditional ERG deletion; scRNA-seq; in vitro co-culture fibroblast activation assay; bleomycin lung fibrosis model Nature communications High 35879310
2023 EVI1 oncogene directly activates ERG transcription by occupying a conserved intragenic ERG enhancer; ERG is selectively required for EVI1-driven AML; ectopic ERG expression rescues AML cell dependence on EVI1, establishing ERG as the major oncogenic effector downstream of EVI1. CRISPR screens; ChIP-seq for EVI1 at ERG enhancer; ERG knockdown causing terminal differentiation; ERG rescue of EVI1-depleted cells; in vivo mouse models Blood High 36095844

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 TNF receptor-deficient mice reveal divergent roles for p55 and p75 in several models of inflammation. Journal of immunology (Baltimore, Md. : 1950) 565 9551933
2016 Deregulation of DUX4 and ERG in acute lymphoblastic leukemia. Nature genetics 248 27776115
2008 A causal role for ERG in neoplastic transformation of prostate epithelium. Proceedings of the National Academy of Sciences of the United States of America 236 18245377
2013 ERG induces androgen receptor-mediated regulation of SOX9 in prostate cancer. The Journal of clinical investigation 228 23426182
2008 Transcription factor Erg regulates angiogenesis and endothelial apoptosis through VE-cadherin. Blood 222 18195090
2015 The oncogene ERG: a key factor in prostate cancer. Oncogene 211 25915839
2000 Caspase activities and tumor necrosis factor receptor R1 (p55) level are elevated in the substantia nigra from parkinsonian brain. Journal of neural transmission (Vienna, Austria : 1996) 206 10821442
1994 Fas antigen and p55 TNF receptor signal apoptosis through distinct pathways. Journal of immunology (Baltimore, Md. : 1950) 202 7509828
2003 FUS/ERG gene fusions in Ewing's tumors. Cancer research 195 12907633
1987 The erg gene: a human gene related to the ets oncogene. Proceedings of the National Academy of Sciences of the United States of America 188 3476934
2015 SPOP Promotes Ubiquitination and Degradation of the ERG Oncoprotein to Suppress Prostate Cancer Progression. Molecular cell 178 26344095
2011 ERG gene rearrangements are common in prostatic small cell carcinomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 167 21336263
1997 Tissue and species distribution of mRNA for the IKr-like K+ channel, erg. Circulation research 150 9012748
1999 Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier. The Journal of clinical investigation 139 10606630
2015 Truncated ERG Oncoproteins from TMPRSS2-ERG Fusions Are Resistant to SPOP-Mediated Proteasome Degradation. Molecular cell 133 26344096
2011 Immunohistochemistry for ERG expression as a surrogate for TMPRSS2-ERG fusion detection in prostatic adenocarcinomas. The American journal of surgical pathology 129 21677539
2002 Functional and pharmacological properties of canine ERG potassium channels. American journal of physiology. Heart and circulatory physiology 104 12388285
2014 TMPRSS2-ERG expression predicts prostate cancer survival and associates with stromal biomarkers. PloS one 100 24505269
2005 The proto-oncogene ERG in megakaryoblastic leukemias. Cancer research 98 16140924
2004 The p55 TNF receptor mediates TNF inhibition of osteoblast differentiation independently of apoptosis. American journal of physiology. Endocrinology and metabolism 98 15625085
2012 Expression of ERG, an Ets family transcription factor, identifies ERG-rearranged Ewing sarcoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 97 22766791
2009 ETS2 and ERG promote megakaryopoiesis and synergize with alterations in GATA-1 to immortalize hematopoietic progenitor cells. Blood 97 19168790
2000 The p55 TNF-alpha receptor plays a critical role in T cell alloreactivity. Journal of immunology (Baltimore, Md. : 1950) 95 10623807
1993 The effects of dystrophin gene mutations on the ERG in mice and humans. Investigative ophthalmology & visual science 92 8258524
2018 Binding of TMPRSS2-ERG to BAF Chromatin Remodeling Complexes Mediates Prostate Oncogenesis. Molecular cell 86 30078722
2017 Significance of the TMPRSS2:ERG gene fusion in prostate cancer. Molecular medicine reports 84 28849022
1996 Identification of anisomycin-activated kinases p45 and p55 in murine cells as MAPKAP kinase-2. Oncogene 83 8632902
2009 Retinal pathway origins of the pattern ERG of the mouse. Experimental eye research 82 19250935
2009 Distinct genomic aberrations associated with ERG rearranged prostate cancer. Genes, chromosomes & cancer 80 19156837
2017 Dynamic regulation of VEGF-inducible genes by an ERK/ERG/p300 transcriptional network. Development (Cambridge, England) 75 28536097
2008 Delineation of TMPRSS2-ERG splice variants in prostate cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 73 18676740
2011 Promotion and maintenance of leukemia by ERG. Blood 72 21321361
2022 Dysfunctional ERG signaling drives pulmonary vascular aging and persistent fibrosis. Nature communications 71 35879310
1997 Ligand-induced formation of p55 and p75 tumor necrosis factor receptor heterocomplexes on intact cells. The Journal of biological chemistry 69 9099731
1999 TNF receptor p55 plays a pivotal role in murine keratinocyte apoptosis induced by ultraviolet B irradiation. Journal of immunology (Baltimore, Md. : 1950) 68 9973400
2016 Integration of tissue metabolomics, transcriptomics and immunohistochemistry reveals ERG- and gleason score-specific metabolomic alterations in prostate cancer. Oncotarget 64 26623558
2014 Heterogeneity and chronology of PTEN deletion and ERG fusion in prostate cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 63 24762546
2002 Regulation of an ERG K+ current by Src tyrosine kinase. The Journal of biological chemistry 63 11834728
2013 The proto-oncogene ERG is a target of microRNA miR-145 in prostate cancer. The FEBS journal 60 23480797
2013 Tumor necrosis factor in traumatic brain injury: effects of genetic deletion of p55 or p75 receptor. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 60 23611870
2004 Functions of erg K+ channels in excitable cells. Journal of cellular and molecular medicine 60 15090257
1998 Distinct adapter proteins mediate acid versus neutral sphingomyelinase activation through the p55 receptor for tumor necrosis factor. Journal of leukocyte biology 60 9620659
1994 ERG gene is translocated in an Ewing's sarcoma cell line. Cancer genetics and cytogenetics 59 8076344
2001 Tumor necrosis factor-alpha and its receptors, p55 and p75, in gingiva of adult periodontitis. Journal of dental research 58 11499508
2009 Trisomy of Erg is required for myeloproliferation in a mouse model of Down syndrome. Blood 57 20007548
2006 Whirlin complexes with p55 at the stereocilia tip during hair cell development. Proceedings of the National Academy of Sciences of the United States of America 57 16829577
2017 Loss of FOXO1 Cooperates with TMPRSS2-ERG Overexpression to Promote Prostate Tumorigenesis and Cell Invasion. Cancer research 53 28986382
2014 TMPRSS2:ERG blocks neuroendocrine and luminal cell differentiation to maintain prostate cancer proliferation. Oncogene 52 25263440
1997 TNF receptor p55 controls early acute graft-versus-host disease. Journal of immunology (Baltimore, Md. : 1950) 52 9164935
2012 Clinical potential of the ERG oncoprotein in prostate cancer. Nature reviews. Urology 51 22331093
1999 Separation of M-like current and ERG current in NG108-15 cells. British journal of pharmacology 51 10455268
1995 Human ERG is a proto-oncogene with mitogenic and transforming activity. Oncogene 51 7731694
2010 ERG rearrangement in small cell prostatic and lung cancer. Histopathology 49 20636794
2011 Oncogenic activation of ERG: A predominant mechanism in prostate cancer. Journal of carcinogenesis 48 22279422
2016 BET bromodomain-mediated interaction between ERG and BRD4 promotes prostate cancer cell invasion. Oncotarget 44 27223260
2013 Monoallelic expression of TMPRSS2/ERG in prostate cancer stem cells. Nature communications 44 23535644
2009 TMPRSS2-ERG gene fusions are infrequent in prostatic ductal adenocarcinomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 44 19151660
1994 TNF-alpha, the great imitator: role of p55 and p75 TNF receptors in hematopoiesis. Stem cells (Dayton, Ohio) 44 7535144
2020 An Erg-driven transcriptional program controls B cell lymphopoiesis. Nature communications 42 32541654
2010 Androgens Induce Functional CXCR4 through ERG Factor Expression in TMPRSS2-ERG Fusion-Positive Prostate Cancer Cells. Translational oncology 42 20563261
2001 Identification of amino acid residues in the ETS transcription factor Erg that mediate Erg-Jun/Fos-DNA ternary complex formation. The Journal of biological chemistry 42 11278640
2021 Dual functions of SPOP and ERG dictate androgen therapy responses in prostate cancer. Nature communications 41 33531470
2020 ERG orchestrates chromatin interactions to drive prostate cell fate reprogramming. The Journal of clinical investigation 41 32701507
2019 ISCEV extended protocol for the S-cone ERG. Documenta ophthalmologica. Advances in ophthalmology 39 31749034
2014 ERG expression in chondrogenic bone and soft tissue tumours. Journal of clinical pathology 38 25378537
2013 Novel dual-color immunohistochemical methods for detecting ERG-PTEN and ERG-SPINK1 status in prostate carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 38 23348902
1994 Expression of TNF-alpha and TNFR p55 in cultured amniochorion. American journal of reproductive immunology (New York, N.Y. : 1989) 38 7880403
2013 Frequent TMPRSS2-ERG rearrangement in prostatic small cell carcinoma detected by fluorescence in situ hybridization: the superiority of fluorescence in situ hybridization over ERG immunohistochemistry. Human pathology 37 23850495
2002 Biophysical properties of heteromultimeric erg K+ channels. Pflugers Archiv : European journal of physiology 36 12466946
2017 Synergistic Role of Endothelial ERG and FLI1 in Mediating Pulmonary Vascular Homeostasis. American journal of respiratory cell and molecular biology 35 28248553
2016 ETS transcription factor ERG cooperates with histone demethylase KDM4A. Oncology reports 35 27109047
2023 EVI1 drives leukemogenesis through aberrant ERG activation. Blood 34 36095844
2016 The ubiquitin ligase TRIM25 targets ERG for degradation in prostate cancer. Oncotarget 34 27626314
2015 Antineoplastic Effects of siRNA against TMPRSS2-ERG Junction Oncogene in Prostate Cancer. PloS one 34 25933120
2001 Selective expression of erg isoforms in human endothelial cells. The international journal of biochemistry & cell biology 34 11312105
1986 Pattern ERG and glaucomatous visual field defects. Documenta ophthalmologica. Advances in ophthalmology 34 3948667
2009 Erythrocyte scaffolding protein p55/MPP1 functions as an essential regulator of neutrophil polarity. Proceedings of the National Academy of Sciences of the United States of America 33 19897731
2018 Docetaxel Treatment in PTEN- and ERG-aberrant Metastatic Prostate Cancers. European urology oncology 32 29911685
2016 Deletion of Interstitial Genes between TMPRSS2 and ERG Promotes Prostate Cancer Progression. Cancer research 32 26880803
2015 Clinical value of ERG, TFF3, and SPINK1 for molecular subtyping of prostate cancer. Cancer 32 25639219
1998 Function of p55 and its nonerythroid homologues. Current opinion in hematology 31 9570704
1995 Genomic structure and nucleotide sequence of the p55 gene of the puffer fish Fugu rubripes. Genomics 31 7558025
2015 Articular cartilage endurance and resistance to osteoarthritic changes require transcription factor Erg. Arthritis & rheumatology (Hoboken, N.J.) 30 26097038
2017 SPOP mutation drives prostate neoplasia without stabilizing oncogenic transcription factor ERG. The Journal of clinical investigation 28 29202479
2004 Muscarinic modulation of erg potassium current. The Journal of physiology 27 15235086
2011 ERG deregulation induces PIM1 over-expression and aneuploidy in prostate epithelial cells. PloS one 26 22140532
2003 Impaired electroretinogram (ERG) response in apolipoprotein E-deficient mice. Current eye research 26 12868005
2013 5' UTR control of native ERG and of Tmprss2:ERG variants activity in prostate cancer. PloS one 25 23472063
2004 A comparison of ERG abnormalities in XLRS and XLCSNB. Documenta ophthalmologica. Advances in ophthalmology 25 15455796
2013 ERG induces epigenetic activation of Tudor domain-containing protein 1 (TDRD1) in ERG rearrangement-positive prostate cancer. PloS one 24 23555854
2008 The role of the ETS factor erg in zebrafish vasculogenesis. Mechanisms of development 24 19027849
2015 Elevated expression of microRNA-30b in osteoarthritis and its role in ERG regulation of chondrocyte. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 23 26653555
2018 Wnt receptor Frizzled 8 is a target of ERG in prostate cancer. The Prostate 22 30051493
2014 Overexpression of ERG in cord blood progenitors promotes expansion and recapitulates molecular signatures of high ERG leukemias. Leukemia 22 25306899
2001 Cloning and characterization of the human retina-specific gene MPP4, a novel member of the p55 subfamily of MAGUK proteins. Genomics 22 11414766
2013 AKT collaborates with ERG and Gata1s to dysregulate megakaryopoiesis and promote AMKL. Leukemia 21 23380710
2013 Evaluation of ERG responsive proteome in prostate cancer. The Prostate 21 24115221
2013 Immunohistochemical evaluation of ERG expression in various benign and malignant tissues. Annals of clinical and laboratory science 20 23462600
2012 The biological function of the WD40 repeat-containing protein p55/Caf1 in Drosophila. Developmental dynamics : an official publication of the American Association of Anatomists 20 22241697
2010 The oncogenic role of the ETS transcription factors MEF and ERG. Cell cycle (Georgetown, Tex.) 20 20814243