Affinage

OVOL2

Transcription factor Ovo-like 2 · UniProt Q9BRP0

Length
275 aa
Mass
30.4 kDa
Annotated
2026-06-10
49 papers in source corpus 31 papers cited in narrative 32 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

OVOL2 is an evolutionarily conserved C2H2 zinc-finger transcriptional repressor that safeguards epithelial identity and governs developmental cell-fate decisions, principally by directly silencing EMT-inducing transcription factors (PMID:24735879, PMID:29872308). Its central regulatory module is a double-negative feedback circuit with ZEB1: OVOL2 binds and represses the ZEB1 promoter, and the two factors mutually inhibit one another to generate stable epithelial, mesenchymal, and intermediate states (PMID:26554584, PMID:29872308). Beyond ZEB1, OVOL2 directly represses Twist1, c-Myc, Notch1, and ID2, thereby restraining EMT, proliferation, terminal differentiation, and stemness across keratinocytes, lung and breast carcinoma, and trophoblast stem cells (PMID:19700410, PMID:27884772, PMID:32244352). OVOL2 also antagonizes signaling inputs that drive mesenchymal programs: it binds the TCF4–β-catenin complex and recruits HDAC1 to block WNT-driven EMT genes, inhibits TGF-β/Smad signaling, and binds NF-κB p65 to favor HDAC1 over p300 recruitment (PMID:26619963, PMID:28455959, PMID:35346238). It acts downstream of BMP/Smad and lineage factors such as Pdx1 to direct fate choices between neuroectoderm and mesendoderm and to maintain β-cell, corneal, and thymic epithelial identity (PMID:23319585, PMID:33989778, PMID:38012144). OVOL2 is required in vivo for cranial neural tube closure, vascular and cardiac development, and epithelial morphogenesis, and its activity is tuned post-translationally by PARP1-mediated PARylation within its zinc-finger domains and by p53/MDM2-controlled ubiquitination (PMID:16423343, PMID:17573777, PMID:30542118, PMID:35896951). Through co-repressor recruitment (HDAC1, HDAC3, NCoR) and disruption of RCOR1-LSD1-mediated H3K4me2 demethylation, OVOL2 enforces transcriptional and epigenetic repression that also restrains aerobic glycolysis and fatty-acid oxidation and supports adaptive thermogenesis (PMID:35896951, PMID:38012144, PMID:38627980, PMID:36228616). In humans, non-coding gain-of-function mutations in the OVOL2 proximal promoter cause the autosomal-dominant corneal endothelial dystrophies CHED1 and PPCD1 (PMID:26749309).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 2006 High

    Established that OVOL2 is essential in vivo before any molecular targets were known, defining its developmental requirement in neural tube, ectodermal patterning, and vascular/cardiac formation.

    Evidence Ovol2 knockout mice with in situ hybridization and marker analysis; endothelial siRNA and Matrigel assay

    PMID:16423343 PMID:17573777

    Open questions at the time
    • Direct transcriptional targets driving these phenotypes not yet identified
    • Did not establish whether defects are cell-autonomous
  2. 2006 Medium

    Placed OVOL2 within an OVOL regulatory hierarchy by showing OVOL1 represses the Ovol2 promoter in a DNA-binding-dependent manner.

    Evidence Ovol1 knockout epidermis analysis, promoter repression assay, qRT-PCR

    PMID:17049212

    Open questions at the time
    • Single lab
    • Functional consequence of OVOL1→OVOL2 repression in vivo not resolved
  3. 2009 High

    Identified the first direct OVOL2 target genes (c-Myc, Notch1), establishing it as a sequence-specific transcriptional repressor coordinating proliferation and differentiation in keratinocytes.

    Evidence ChIP, luciferase reporter, and functional rescue with siRNA knockdown in HaCaT cells

    PMID:19700410

    Open questions at the time
    • Co-repressor machinery not defined
    • Limited to keratinocyte context
  4. 2013 High

    Defined OVOL2 as a downstream effector of BMP/Smad signaling that biases neuroectoderm-versus-mesendoderm fate decisions.

    Evidence ES cell differentiation, ChIP of Smad1/5/8 at Ovol2 intron 2, chick embryo electroporation

    PMID:23319585

    Open questions at the time
    • Downstream targets mediating mesendoderm induction not fully mapped
  5. 2013 Medium

    Generalized OVOL2 function to cancer by showing OVOL-TFs drive MET via a ZEB1 feedback loop and induce ESRP1-dependent splicing, attenuating metastasis.

    Evidence Overexpression in cancer lines, mouse prostate tumor models, expression survey across 917 lines

    PMID:24124593

    Open questions at the time
    • Directness of ZEB1 feedback established later
    • Single lab
  6. 2014 High

    Demonstrated in vivo that OVOL2 loss converts the TGF-β response from growth arrest to EMT, and that the repressor isoform reprograms metastatic cells back to epithelial state.

    Evidence Conditional Ovol2 knockout mice, mammary morphogenesis, forced expression rescue in cancer cells

    PMID:24735879

    Open questions at the time
    • Full repertoire of repressed EMT inducers not enumerated
  7. 2014 High

    Revealed an activating (non-repressive) mode of OVOL2 action through direct nuclear interaction with ER71/ETV2 to drive endothelial/hematopoietic specification.

    Evidence Co-IP, Flk1 promoter luciferase, shRNA knockdown in ES cell differentiation

    PMID:25267199

    Open questions at the time
    • How OVOL2 switches between repressor and co-activator roles unknown
  8. 2015 High

    Mechanistically linked OVOL2 to WNT antagonism by showing it binds TCF4/β-catenin and recruits HDAC1 to repress WNT-EMT genes, with in vivo tumor relevance.

    Evidence Tandem affinity purification, Co-IP, luciferase, intestine-specific KO and Apc(min/+) cross

    PMID:26619963

    Open questions at the time
    • Whether HDAC1 recruitment is universal across OVOL2 targets not established
  9. 2015 Medium

    Formalized the OVOL2–ZEB1 double-negative feedback loop as the bistable switch generating intermediate EMT states.

    Evidence Mathematical modeling with experimental measurement of Ovol2/Zeb1 in intermediate states

    PMID:26554584

    Open questions at the time
    • Systems-level inference; in vivo proof of intermediate-state control limited
  10. 2015 High

    Connected OVOL2 to human disease, showing promoter mutations cause CHED1/PPCD1 via gain-of-function aberrant expression in corneal endothelium.

    Evidence Pedigree sequencing plus in vitro promoter luciferase activity across four mutations

    PMID:26749309

    Open questions at the time
    • In vivo demonstration of corneal endothelial dysregulation by mutant promoters not shown
  11. 2016 Medium

    Extended the direct repressor target set to Twist1, broadening OVOL2's EMT-suppressive reach to lung adenocarcinoma.

    Evidence Luciferase, ChIP, Transwell/wound healing, rescue in lung cancer cells

    PMID:27884772

    Open questions at the time
    • Single lab
    • In vivo confirmation absent
  12. 2017 Medium

    Showed OVOL2 antagonizes TGF-β at multiple nodes (Smad4 suppression, Smad7 induction, blocking Smad4 DNA binding and Smad2/3 complex formation).

    Evidence Overexpression/knockdown in mammary tumor cells, RT-PCR, Co-IP, in vivo tumor models

    PMID:28455959

    Open questions at the time
    • Whether effects are direct vs. secondary to EMT reversal not fully separated
  13. 2017 Medium

    Reinforced the OVOL1→OVOL2/c-Myc hierarchy in squamous carcinoma, placing OVOL2 downstream of OVOL1.

    Evidence siRNA knockdown in A431 cells, RT-PCR, Western, IHC in clinical samples

    PMID:28339425

    Open questions at the time
    • Single cell line
    • Directionality of OVOL2 effects on c-Myc not resolved here
  14. 2018 High

    Uncovered post-translational control: PARP1 PARylates OVOL2 within its zinc fingers, altering its repression of Skp2 and driving chromosomal instability.

    Evidence Proteomics, site-directed mutagenesis (K145/176/212A), Co-IP, ChIP, xenograft and MMTV-PyVT models

    PMID:30542118

    Open questions at the time
    • Stimuli triggering PARylation in vivo not defined
  15. 2018 Medium

    Established OVOL2 as an epigenetic repressor of fibroblast identity capable of cooperating with KLF4/TP63 to reprogram cells toward epithelial lineages.

    Evidence Overexpression in dermal fibroblasts, ATAC-seq, motif enrichment

    PMID:31019211

    Open questions at the time
    • Co-repressor mediating chromatin closure not identified in this study
  16. 2018 High

    Defined a ZEB1-dependent cellular mechanism: OVOL2 controls directional keratinocyte/stem-cell migration via repression of Zeb1, shown by genetic epistasis.

    Evidence Conditional and Ovol2/Zeb1 double KO mice, live imaging, wound-healing and anagen assays

    PMID:30413481

    Open questions at the time
    • Molecular link between ZEB1 and directional cytoskeletal control not detailed
  17. 2018 Medium

    Implicated TEAD3/YAP-driven OVOL2 downregulation in trophoblast EMT during implantation, situating OVOL2 in placental epithelial control.

    Evidence Trophoblast co-culture, OVOL2 overexpression/knockdown, RT-PCR, Western

    PMID:29394105

    Open questions at the time
    • Direct OVOL2 promoter occupancy at ZEB1/SNAI2 in trophoblast not shown
  18. 2019 Medium

    Showed OVOL2 maintains corneal epithelial lineage identity, with loss producing neural-like fate, and enabling fibroblast-to-corneal-epithelial reprogramming.

    Evidence TF overexpression in human fibroblasts and OVOL2 knockdown in corneal epithelial cells

    PMID:31403532

    Open questions at the time
    • Direct target genes in cornea not mapped
    • Single lab
  19. 2020 High

    Identified ID2 as a direct OVOL2 target whose repression promotes trophoblast stem-cell differentiation.

    Evidence ChIP, ectopic OVOL2 and Ovol2 KO in TS cells, ID2 overexpression rescue

    PMID:32244352

    Open questions at the time
    • Co-repressor recruitment at ID2 locus not characterized
  20. 2021 Medium

    Defined a Pdx1/Ovol2/Zeb2 axis preserving β-cell identity, where OVOL2 loss permits Zeb2-driven mesenchymal reprogramming relevant to diabetes.

    Evidence Bulk and scRNA-seq, loss/gain-of-function in MIN6 and EndoC-βH1, T2D datasets

    PMID:33989778

    Open questions at the time
    • Direct OVOL2 binding at Zeb2 promoter not shown here
    • Single lab
  21. 2021 Medium

    Linked OVOL2 to MAP3K8/AKT/NF-κB suppression as a mechanism of EMT inhibition in colorectal cancer.

    Evidence RNA-seq and ChIP-seq cross-referencing, wound-healing/Transwell, overexpression/knockdown

    PMID:34098198

    Open questions at the time
    • Direct vs. indirect regulation of MAP3K8 not fully resolved
  22. 2022 Medium

    Showed OVOL2 represses aerobic glycolysis via NCoR/HDAC3 recruitment, and is itself stabilized by p53 through inhibition of MDM2-mediated degradation.

    Evidence Overexpression/KO, Co-IP for NCoR/HDAC3, glycolysis and ubiquitination assays

    PMID:35896951

    Open questions at the time
    • Glycolytic gene targets bound directly not exhaustively mapped
  23. 2022 Medium

    Demonstrated OVOL2 binds NF-κB p65 to swap p300 for HDAC1, suppressing GLUT1-driven glucose import, while NF-κB reciprocally degrades OVOL2.

    Evidence Co-IP, luciferase, xenografts, Western, immunostaining

    PMID:35346238

    Open questions at the time
    • E3 ligase mediating NF-κB-driven OVOL2 degradation not identified
  24. 2022 Medium

    Revealed transcriptional repression of RhoU/RhoJ as the basis for OVOL2-induced mitotic block and reduced invasiveness in anaplastic thyroid cancer.

    Evidence Overexpression, RNA-seq, ChIP-seq, RhoU/RhoJ knockdown, spindle imaging

    PMID:35337349

    Open questions at the time
    • Single lab
    • In vivo relevance not established
  25. 2022 High

    Established a non-EMT physiological role: OVOL2 is required for adaptive thermogenesis and limits white adipogenesis by blocking C/EBPα target engagement, controlling energy expenditure.

    Evidence ENU hypomorphic (boh) allele, pair-feeding, metabolic cages, adipocyte overexpression, Lepob/ob cross

    PMID:36228616

    Open questions at the time
    • Mechanism of C/EBPα blockade at molecular level not detailed
  26. 2022 High

    Defined an epigenetic mechanism for epithelial identity maintenance: OVOL2 disrupts RCOR1-LSD1 within the BRAF-HDAC complex to block H3K4me2 demethylation in thymic epithelium.

    Evidence Viable C120Y missense allele, TEC-specific deletion, Co-IP, chromatin accessibility and H3K4me2 assays

    PMID:38012144

    Open questions at the time
    • Whether LSD1 disruption operates at OVOL2's classic EMT targets unknown
  27. 2022 Medium

    Distinguished isoform-specific functions, with the repressor-domain Ovol2a regulating EMT genes/pluripotency and Ovol2b lacking the repressor domain activating PGC-specification genes.

    Evidence Splice-variant-specific KO/KI in mouse embryos, transcriptome and direct target analysis

    PMID:35029669

    Open questions at the time
    • Mechanism by which Ovol2b activates genes not defined
  28. 2024 Medium

    Linked OVOL2 loss to fatty-acid-oxidation-fueled cancer stemness via direct JAK repression and HDAC1 recruitment to STAT3, reducing CPT1A/CPT1B activation.

    Evidence PyVT-Ovol2 KO mice, Co-IP, ChIP/luciferase at JAK promoter, FAO inhibitor, sphere assay

    PMID:38627980

    Open questions at the time
    • Single lab
    • Generality across tumor types not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How OVOL2 toggles between transcriptional repressor and co-activator modes, and how its post-translational modifications (PARylation, ubiquitination) are spatiotemporally coordinated to select context-specific target repertoires, remains unresolved.
  • No unified structural or biochemical model of OVOL2 cofactor switching
  • Determinants of tissue-specific target selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4 GO:0060089 molecular transducer activity 4
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1430728 Metabolism 3 R-HSA-4839726 Chromatin organization 2
Partners
CTNNB1ETV2HDAC1HDAC3NCOR1RELATCF4ZEB1

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 OVOL2 directly represses c-Myc and Notch1 transcription in keratinocytes, thereby suppressing transient proliferation and terminal differentiation, respectively. This was established by chromatin immunoprecipitation, luciferase reporter, and functional rescue assays. ChIP, luciferase reporter assay, functional rescue assay, siRNA knockdown in HaCaT cells The Journal of biological chemistry High 19700410
2014 OVOL2 acts as a transcriptional repressor that directly represses myriad EMT inducers in mammary epithelial cells. Its absence switches TGF-β response from growth arrest to EMT. Forced expression of the repressor isoform of OVOL2 reprograms metastatic breast cancer cells from mesenchymal to epithelial state. Conditional Ovol2 knockout mice, in vivo mammary morphogenesis assay, forced expression in cancer cells, molecular characterization of TGF-β response Developmental cell High 24735879
2013 OVOL1 and OVOL2 induce mesenchymal-to-epithelial transition (MET) in human cancers via a regulatory feedback loop with EMT-inducing transcription factor ZEB1, and regulate mRNA splicing by inducing ESRP1. Expression of OVOL-TFs in mesenchymal prostate cancer cells attenuates metastatic potential in mouse tumor models. Overexpression in cancer cell lines, mouse prostate tumor models, expression analysis across 917 cancer cell lines PloS one Medium 24124593
2015 OVOL2 and ZEB1 form a mutual inhibitory circuit (double-negative feedback loop). Evidence for direct mutual inhibition was obtained experimentally; this circuit generates multiple intermediate EMT states and modulates bidirectional transitions between epithelial and mesenchymal states. Mathematical modeling integrated with experimental validation; measurement of Ovol2 and Zeb1 expression in intermediate cell states PLoS computational biology Medium 26554584
2015 OVOL2 inhibits WNT signaling by binding TCF4 and β-catenin and facilitating recruitment of histone deacetylase 1 (HDAC1) to the TCF4–β-catenin complex, thereby inhibiting expression of WNT-regulated EMT genes (e.g., SLUG). The OVOL2-containing complex was purified by tandem affinity purification and confirmed by co-immunoprecipitation. Tandem affinity purification, co-immunoprecipitation, luciferase reporter assays, lentiviral overexpression, intestine-specific Ovol2 knockout mice, Apc(min/+) cross Gastroenterology High 26619963
2015 Non-coding mutations in the OVOL2 proximal promoter cause autosomal-dominant corneal endothelial dystrophies CHED1 and PPCD1. All four mutated OVOL2 promoters showed increased transcriptional activity compared to wild-type in vitro, indicating gain-of-function aberrant OVOL2 expression in corneal endothelium as disease mechanism. OVOL2 is a direct transcriptional repressor of ZEB1. Targeted and whole-genome sequencing, direct promoter sequencing in pedigrees, in vitro luciferase transcriptional activity assays American journal of human genetics High 26749309
2006 Ovol2 is required for cranial neural tube development, neural crest cell migration and survival, and proper ectodermal patterning in mice. Ovol2 knockout results in lethality by E10.5 with open cranial neural tube, improper Shh expression, and lateral shift of neuroectoderm/surface ectoderm border. Ovol2 gene knockout mice, in situ hybridization, immunostaining, marker expression analysis Developmental biology High 16423343
2007 Ovol2 is required for extraembryonic and embryonic vascularization and heart formation in mice. Ovol2-deficient mice die at E9.5–10.5 due to vascular and cardiac defects. In an endothelial cell line, siRNA knockdown of Ovol2 inhibited capillary-like network formation on Matrigel. Gene-targeted Ovol2 knockout mice, siRNA knockdown in endothelial cells, Matrigel capillary formation assay Genes to cells : devoted to molecular & cellular mechanisms High 17573777
2006 OVOL2 is a downstream target of OVOL1: Ovol1 represses Ovol2 promoter activity in a DNA binding-dependent manner, and Ovol2 expression is upregulated in Ovol1-deficient epidermis. Ovol1 knockout mouse analysis, promoter repression assay (DNA binding-dependent), qRT-PCR Biochimica et biophysica acta Medium 17049212
2013 Ovol2 acts downstream of the BMP signaling pathway: BMP4 directly regulates Ovol2 expression through binding of Smad1/5/8 to the second intron of the Ovol2 gene. Ovol2 in turn promotes mesendodermal and inhibits neural differentiation, mediating BMP-directed cell fate decisions between neuroectoderm and mesendoderm. ES cell differentiation assays, Ovol2 knockdown and overexpression, ChIP showing Smad1/5/8 binding to Ovol2 intron 2, chick embryo electroporation The Journal of biological chemistry High 23319585
2014 OVOL2 directly interacts with ER71/ETV2 transcription factor in the nucleus (but not with ETS1 or ETS2). This interaction enhances ER71-mediated activation of the Flk1 promoter and is critical for generation of FLK1+, endothelial, and hematopoietic cells from embryonic stem cells. Co-immunoprecipitation, luciferase reporter assay (Flk1 promoter), shRNA-mediated knockdown, ES cell differentiation assay Blood High 25267199
2016 OVOL2 directly represses Twist1 transcription in lung adenocarcinoma cells by binding to the Twist1 promoter, thereby suppressing EMT-associated migration and invasion. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), Transwell and wound healing assays, rescue experiment Gene Medium 27884772
2017 OVOL2 inhibits TGF-β signaling at multiple levels: it inhibits Smad4 mRNA expression, induces Smad7 mRNA expression, blocks Smad4 binding to target DNA, and interferes with complex formation between Smad4 and Smad2/3, thereby antagonizing TGF-β-induced EMT in mammary tumor cells. Overexpression and knockdown in mammary tumor cell lines, RT-PCR, co-immunoprecipitation, in vivo mouse tumor models Oncotarget Medium 28455959
2018 OVOL2 directly suppresses ZEB1 transcription in osteosarcoma cells by binding to the ZEB1 promoter, as demonstrated by luciferase reporter assay and ChIP. Luciferase reporter assay, ChIP, overexpression in MG-63 and SW1353 cells, immunohistochemistry in patient OS tissues OncoTargets and therapy Medium 29872308
2018 OVOL2 is PARylated by PARP1 at Lysine 145, Lysine 176, and Lysine 212 within its C2H2 zinc finger domains. PARylated OVOL2 alters cell morphology, induces lagging chromosomes and aneuploidy, elevates Cyclin E protein stability, and transcriptionally represses Skp2 (E3 ubiquitin ligase of Cyclin E), as mapped by ChIP. Proteomic approach to identify PARP1 substrate, site-specific mutagenesis (K145/176/212A), Co-IP, ChIP mapping of Skp2 promoter binding site, xenograft and MMTV-PyVT transgenic mouse models Oncogene High 30542118
2018 OVOL2 overexpression in fibroblasts suppresses fibroblast-associated gene loci (chromatin becomes inaccessible at OVOL2 target loci) and facilitates reprogramming into epithelial lineages cooperatively with KLF4 and TP63. OVOL2 acts as a transcriptional repressor of fibroblast identity genes. Overexpression in dermal fibroblasts, ATAC-seq (chromatin accessibility), motif enrichment analysis, co-expression with KLF4/TP63/HNF1A Scientific reports Medium 31019211
2018 OVOL2 downregulation in bovine trophoblasts during implantation occurs via the TEAD3/YAP signaling pathway and results in upregulation of ZEB1, SNAI2, and mesenchymal markers. OVOL2 overexpression decreases ZEB1 transcripts and increases E-cadherin in trophoblast cells. Global expression analysis, trophoblast attachment co-culture system, OVOL2 overexpression and knockdown, RT-PCR, Western blot FASEB journal Medium 29394105
2018 Deletion of Ovol2 in mouse skin epithelium impairs directional migration (increased speed but reduced directionality) and proliferation of keratinocytes and bulge hair follicle stem cells. Simultaneous deletion of Zeb1 restores directional migration to Ovol2-deficient cells, placing Zeb1 downstream of Ovol2 in this process. Live imaging and genetic epistasis established these relationships. Conditional Ovol2 KO mice, Ovol2/Zeb1 double KO epistasis, live imaging of wound explants and Bu-HFSCs, wound healing and anagen assays EMBO reports High 30413481
2019 OVOL2 overexpression (along with PAX6 and KLF4) directly reprograms human fibroblasts into corneal epithelial cell-like cells. Suppression of OVOL2 in corneal epithelial cells induces qualities consistent with neural lineage cells, indicating OVOL2 maintains corneal epithelial lineage identity. Transcription factor overexpression in human fibroblasts, loss-of-function (OVOL2 knockdown) in corneal epithelial cells Cornea Medium 31403532
2020 OVOL2 directly binds to and represses the ID2 gene locus in trophoblast stem cells, and directly represses ID2 transcriptional activity. OVOL2-driven repression of ID2 promotes TS cell differentiation; overexpression of ID2 alone is sufficient to reinforce the TS cell stem state. ChIP (OVOL2 binding proximal to ID2 gene), ectopic OVOL2 expression in TS cells, Ovol2 KO TS cells, ID2 overexpression rescue assay Cells High 32244352
2021 In pancreatic β-cells, Pdx1 transactivates Ovol2, which in turn represses Zeb2. Loss of Pdx1 reduces OVOL2 protein, triggering Zeb2-mediated mesenchymal reprogramming of β-cells. Loss- and gain-of-function experiments in MIN6 and EndoC-βH1 cell lines established this Pdx1/Ovol2/Zeb2 axis. Bulk and single-cell RNA-seq, loss- and gain-of-function in MIN6 and EndoC-βH1 cells, analysis of T2D mouse and human datasets Molecular metabolism Medium 33989778
2022 OVOL2 represses aerobic glycolysis in breast cancer by recruiting NCoR (nuclear receptor co-repressor) and HDAC3 to directly repress expression of glycolytic genes. The tumor suppressor p53 activates OVOL2 by binding MDM2 and inhibiting MDM2-mediated ubiquitination and degradation of OVOL2, establishing a p53/MDM2/OVOL2 axis. In vitro and in vivo overexpression/KO studies, Co-IP for NCoR/HDAC3 interaction, glycolysis assays, ubiquitination assay Advanced science Medium 35896951
2022 OVOL2 directly binds P65 (NF-κB subunit) and inhibits recruitment of P300 while facilitating HDAC1 binding to P65, thereby suppressing NF-κB signaling and GLUT1 translocation/glucose import in NSCLC. Conversely, NF-κB signaling negatively regulates OVOL2 expression via the ubiquitin-proteasome pathway. Co-immunoprecipitation, luciferase assay, xenograft mouse models, Western blot, immunostaining Cell communication and signaling Medium 35346238
2022 OVOL2 transcriptionally inhibits RhoU and RhoJ (RHO GTPase pathway members) in anaplastic thyroid cancer cells, causing G2/M cell cycle block, mitotic spindle abnormalities, and reduced invasiveness. Silencing of RhoU alone recapitulated the OVOL2-driven phenotype. OVOL2 new direct target genes were identified by RNA-seq and ChIP-seq. OVOL2 overexpression in ATC cell lines, RNA-seq, ChIP-seq, RhoU/RhoJ knockdown, cell cycle analysis, immunofluorescence of mitotic spindle Journal of experimental & clinical cancer research Medium 35337349
2022 OVOL2 is required for thermogenesis in brown/beige adipose tissue and limits white adipogenesis. In white adipose tissue, OVOL2 inhibited adipogenesis by blocking C/EBPα engagement of its transcriptional targets. Identified via random germline mutagenesis (hypomorphic boh allele causing obesity). ENU-mutagenesis hypomorphic mouse allele (boh), pair-feeding experiments, Ovol2 overexpression in adipocytes, cold tolerance tests, Lepob/ob cross Cell metabolism High 36228616
2022 OVOL2 sustains postnatal thymic epithelial cell (TEC) identity by inhibiting the epigenetic regulatory BRAF-HDAC complex, specifically disrupting RCOR1-LSD1 interaction, which causes inhibition of LSD1-mediated H3K4me2 demethylation, resulting in chromatin accessibility and transcriptional activation of epithelial genes. A missense allele (C120Y) established this mechanism. Viable Ovol2 missense (C120Y) mouse allele, TEC-specific Cre deletion, Co-IP for BRAF-HDAC/RCOR1-LSD1 interaction, chromatin accessibility assays, H3K4me2 demethylation assays Nature communications High 38012144
2022 A viable hypomorphic Ovol2 allele in mice (boh) reveals that OVOL2 is required for normal energy expenditure. OVOL2-deficient mice develop obesity with normal food intake but decreased energy expenditure, extreme cold intolerance, and insulin resistance. Random germline mutagenesis, pair-feeding, metabolic cage analysis, body composition measurement Cell metabolism High 36228616
2024 Loss of OVOL2 in triple-negative breast cancer promotes fatty acid oxidation (FAO) fueling stemness. Mechanistically, OVOL2 suppresses STAT3 phosphorylation by directly inhibiting JAK transcription and recruits HDAC1 to STAT3, reducing transcriptional activation of CPT1A and CPT1B (FAO rate-limiting enzymes). OVOL2 KO mice (PyVT-Ovol2 KO), Co-IP for HDAC1-STAT3 interaction, luciferase and ChIP for JAK promoter, FAO inhibitor treatment, sphere-forming assay Advanced science Medium 38627980
2011 Ovol2/MOVO protein localizes to the XY body in spermatocytes at the pachytene stage. In a reporter assay, Ovol2/MOVO repressed histone H1t promoter activity in a spermatogenic cell line, suggesting a role in XY body-associated gene repression during spermatogenesis. Immunohistochemistry with anti-Ovol2 antiserum in mouse testes, luciferase reporter assay (H1t promoter) in GC-2spd cells Journal of andrology Medium 21636736
2022 Ovol2a splice variant (encoding repressor domain) directly regulates EMT-related genes and induces re-acquisition of pluripotency potential during primordial germ cell (PGC) specification, while Ovol2b splice variant (lacking the repressor domain) directly upregulates genes associated with PGC specification. These functions were established in mouse epiblast during gastrulation. Splice variant-specific knockout/knockin in mouse embryos, transcriptome analysis, direct gene target identification Development (Cambridge, England) Medium 35029669
2021 OVOL2 inhibits EMT in colorectal cancer cells by blocking the MAP3K8/AKT/NF-κB signaling pathway, identified by cross-referencing ChIP-seq data with RNA-seq differentially expressed genes in OVOL2-overexpressing vs. knockdown cells. RNA-seq, ChIP-seq (GSM1239518), wound-healing and Transwell assays, overexpression and knockdown in HCT116/SW480 cells Pathology, research and practice Medium 34098198
2017 In cutaneous squamous cell carcinoma, OVOL1 is an upstream suppressor of OVOL2 and c-Myc: knockdown of OVOL1 using siRNA increased mRNA and protein levels of both c-Myc and OVOL2. Knockdown of OVOL2 did not significantly affect c-Myc or OVOL1 levels. siRNA knockdown of OVOL1 and OVOL2 in A431 SCC cell line, RT-PCR, Western blot, immunohistochemistry in clinical samples Modern pathology Medium 28339425

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 An Ovol2-Zeb1 Mutual Inhibitory Circuit Governs Bidirectional and Multi-step Transition between Epithelial and Mesenchymal States. PLoS computational biology 214 26554584
2013 Transcription factors OVOL1 and OVOL2 induce the mesenchymal to epithelial transition in human cancer. PloS one 198 24124593
2014 Mammary morphogenesis and regeneration require the inhibition of EMT at terminal end buds by Ovol2 transcriptional repressor. Developmental cell 160 24735879
2015 Autosomal-Dominant Corneal Endothelial Dystrophies CHED1 and PPCD1 Are Allelic Disorders Caused by Non-coding Mutations in the Promoter of OVOL2. American journal of human genetics 63 26749309
2006 The mouse Ovol2 gene is required for cranial neural tube development. Developmental biology 59 16423343
2006 Strain-dependent perinatal lethality of Ovol1-deficient mice and identification of Ovol2 as a downstream target of Ovol1 in skin epidermis. Biochimica et biophysica acta 55 17049212
2018 OVOL2 links stemness and metastasis via fine-tuning epithelial-mesenchymal transition in nasopharyngeal carcinoma. Theranostics 54 29721073
2015 OVOL2, an Inhibitor of WNT Signaling, Reduces Invasive Activities of Human and Mouse Cancer Cells and Is Down-regulated in Human Colorectal Tumors. Gastroenterology 50 26619963
2009 Ovol2 suppresses cell cycling and terminal differentiation of keratinocytes by directly repressing c-Myc and Notch1. The Journal of biological chemistry 49 19700410
2018 The role of the OVOL1-OVOL2 axis in normal and diseased human skin. Journal of dermatological science 45 29454536
2007 Ovol2/Movo, a homologue of Drosophila ovo, is required for angiogenesis, heart formation and placental development in mice. Genes to cells : devoted to molecular & cellular mechanisms 45 17573777
2002 Ovol2, a mammalian homolog of Drosophila ovo: gene structure, chromosomal mapping, and aberrant expression in blind-sterile mice. Genomics 45 12213202
2019 OVOL2 induces mesenchymal-to-epithelial transition in fibroblasts and enhances cell-state reprogramming towards epithelial lineages. Scientific reports 36 31019211
2018 An Ovol2-Zeb1 transcriptional circuit regulates epithelial directional migration and proliferation. EMBO reports 33 30413481
2017 OVOL2 antagonizes TGF-β signaling to regulate epithelial to mesenchymal transition during mammary tumor metastasis. Oncotarget 33 28455959
2022 Transcriptional Repression of Aerobic Glycolysis by OVOL2 in Breast Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 32 35896951
2017 Potential role of the OVOL1-OVOL2 axis and c-Myc in the progression of cutaneous squamous cell carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 32 28339425
2018 Down-regulation of transcription factor OVOL2 contributes to epithelial-mesenchymal transition in a noninvasive type of trophoblast implantation to the maternal endometrium. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 29394105
2016 Ovol2 gene inhibits the Epithelial-to-Mesenchymal Transition in lung adenocarcinoma by transcriptionally repressing Twist1. Gene 30 27884772
2013 The zinc finger transcription factor Ovol2 acts downstream of the bone morphogenetic protein pathway to regulate the cell fate decision between neuroectoderm and mesendoderm. The Journal of biological chemistry 29 23319585
2021 Dysregulation of the Pdx1/Ovol2/Zeb2 axis in dedifferentiated β-cells triggers the induction of genes associated with epithelial-mesenchymal transition in diabetes. Molecular metabolism 25 33989778
2014 OVOL2 is a critical regulator of ER71/ETV2 in generating FLK1+, hematopoietic, and endothelial cells from embryonic stem cells. Blood 25 25267199
2020 OVOL2-Mediated ZEB1 Downregulation May Prevent Promotion of Actinic Keratosis to Cutaneous Squamous Cell Carcinoma. Journal of clinical medicine 24 32106476
2016 Activation of the OVOL1-OVOL2 Axis in the Hair Bulb and in Pilomatricoma. The American journal of pathology 24 26873447
2018 Ovol2 induces mesenchymal-epithelial transition via targeting ZEB1 in osteosarcoma. OncoTargets and therapy 23 29872308
2017 Confirmation of the OVOL2 Promoter Mutation c.-307T>C in Posterior Polymorphous Corneal Dystrophy 1. PloS one 19 28046031
2019 Alterations in GRHL2-OVOL2-ZEB1 axis and aberrant activation of Wnt signaling lead to altered gene transcription in posterior polymorphous corneal dystrophy. Experimental eye research 16 31233731
2019 Direct Reprogramming Into Corneal Epithelial Cells Using a Transcriptional Network Comprising PAX6, OVOL2, and KLF4. Cornea 16 31403532
2020 The Transcription Factor OVOL2 Represses ID2 and Drives Differentiation of Trophoblast Stem Cells and Placental Development in Mice. Cells 15 32244352
2022 OVOL2 impairs RHO GTPase signaling to restrain mitosis and aggressiveness of Anaplastic Thyroid Cancer. Journal of experimental & clinical cancer research : CR 14 35337349
2022 Obesity caused by an OVOL2 mutation reveals dual roles of OVOL2 in promoting thermogenesis and limiting white adipogenesis. Cell metabolism 14 36228616
2016 Expression of Ovol2 is related to epithelial characteristics and shows a favorable clinical outcome in hepatocellular carcinoma. OncoTargets and therapy 14 27729805
2024 Loss of OVOL2 in Triple-Negative Breast Cancer Promotes Fatty Acid Oxidation Fueling Stemness Characteristics. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 12 38627980
2022 An NF-κB/OVOL2 circuit regulates glucose import and cell survival in non-small cell lung cancer. Cell communication and signaling : CCS 10 35346238
2011 Restricted expression of Ovol2/MOVO in XY body of mouse spermatocytes at the pachytene stage. Journal of andrology 10 21636736
2022 Dual role of Ovol2 on the germ cell lineage segregation during gastrulation in mouse embryogenesis. Development (Cambridge, England) 9 35029669
2023 OVOL2: an epithelial lineage determiner with emerging roles in energy homeostasis. Trends in cell biology 8 37336658
2018 Poly(ADP-ribosyl)ation of OVOL2 regulates aneuploidy and cell death in cancer cells. Oncogene 8 30542118
2021 OVOL2 attenuates the expression of MAP3K8 to suppress epithelial mesenchymal transition in colorectal cancer. Pathology, research and practice 5 34098198
2019 Ovol2, a zinc finger transcription factor, is dispensable for spermatogenesis in mice. Reproductive biology and endocrinology : RB&E 5 31759386
2024 OVOL2 induces autophagy-mediated epithelial-mesenchymal transition by the ERK1/2 MAPK signaling in lung adenocarcinoma. iScience 4 38318371
2022 c.-61G>A in OVOL2 is a Pathogenic 5' Untranslated Region Variant Causing Posterior Polymorphous Corneal Dystrophy 1. Cornea 4 34469340
2022 Altered Epithelial-mesenchymal Plasticity as a Result of Ovol2 Deletion Minimally Impacts the Self-renewal of Adult Mammary Basal Epithelial Cells. Journal of mammary gland biology and neoplasia 4 34984648
2023 OVOL2 sustains postnatal thymic epithelial cell identity. Nature communications 3 38012144
2022 Ovo Like Zinc Finger 2 (OVOL2) Suppresses Breast Cancer Stem Cell Traits and Correlates with Immune Cells Infiltration. Breast cancer (Dove Medical Press) 2 35996562
2022 Expression of epithelial-mesenchymal transition biomarkers: Discoidin domain receptor 2, Snail-1, and Ovol-2 as predictors of clinical outcome in patients with epithelial ovarian carcinoma. Journal of cancer research and therapeutics 2 36149163
2024 Ovol2 promoter mutations in mice and human illuminate species-specific phenotypic divergence. Human molecular genetics 1 37971355
2026 Sulconazole Suppresses Colorectal Cancer Immune Evasion by Inhibiting Glycolysis to Upregulate OVOL2 PARylation and Induce PANoptosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 42252920
2024 Disruption of OVOL2 Distal Regulatory Elements as a Possible Mechanism Implicated in Corneal Endothelial Dystrophy. Human mutation 0 40225920

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