Affinage

TBX2

T-box transcription factor TBX2 · UniProt Q13207

Length
712 aa
Mass
75.1 kDa
Annotated
2026-04-28
100 papers in source corpus 41 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TBX2 is a T-box transcription factor that functions as a transcriptional repressor to control cell proliferation, differentiation, and tissue patterning across multiple organ systems. It binds variant T-box elements as a monomer through its T-box DNA-binding domain and recruits corepressor complexes—including HDAC1 and an HP1/KAP1/EZH2/G9A chromatin-silencing module—to establish repressive histone marks (H3K9me3) at target promoters such as p14ARF, p21WAF1, PTEN, E-cadherin, Cx40/Cx43, and Grem1, thereby suppressing senescence, blocking differentiation, and promoting proliferation (PMID:11062467, PMID:14996726, PMID:31253870, PMID:26686089). In the heart, TBX2 maintains atrioventricular canal identity by repressing chamber-specific genes, and its loss causes accessory pathway formation and ventricular preexcitation; in the cochlea, TBX2 is the master determinant of inner hair cell versus outer hair cell fate, with its deletion or ectopic expression sufficient to switch cell identity (PMID:15042700, PMID:21266775, PMID:35508658). TBX2 activity is regulated by BMP2/Smad signaling, Mitf-dependent transcription, p38 MAPK phosphorylation, interaction with hypophosphorylated Rb1, and antagonism by Tbx20-mediated Smad sequestration and PML/p130/E2F4-dependent transcriptional repression of the TBX2 locus (PMID:11087629, PMID:18025091, PMID:20534814, PMID:19661464, PMID:22002537). Partial loss-of-function TBX2 variants (R20Q, R305H) have been identified in patients with a DiGeorge-like syndrome (PMID:29726930).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Establishing TBX2 as a transcriptional repressor: TBX2 was shown to directly bind melanocyte promoter elements (MSEu/MSEi) and repress target gene (TRP-1) transcription, demonstrating that a T-box family member could function as a repressor rather than an activator.

    Evidence EMSA, site-directed mutagenesis, and cotransfection reporter assays in melanocyte/melanoma cells

    PMID:9710594

    Open questions at the time
    • No corepressor mechanism identified
    • Repression domain not yet mapped
  2. 2000 High

    Linking TBX2 repression to senescence bypass and cancer: TBX2 was identified as an immortalizing factor that represses the p19ARF/p14ARF locus, explaining how overexpression could bypass oncogene-induced senescence—a central question for its oncogenic role.

    Evidence Genetic senescence bypass screen in Bmi1-deficient MEFs; promoter repression assays; binding to a variant T-site in the ARF promoter confirmed by mutagenesis

    PMID:11062467 PMID:12000749

    Open questions at the time
    • Chromatin mechanism of repression at the ARF locus not determined
    • In vivo tumor suppressor pathway bypass not yet shown
  3. 2000 High

    Defining upstream regulators: Mitf and BMP2 signaling were established as direct transcriptional activators of TBX2, placing it within defined developmental and lineage-specific signaling cascades in melanocytes and cardiogenesis.

    Evidence Mitf binding to E-box in TBX2 promoter by EMSA with mutagenesis; BMP2 bead implantation in chick embryos and analysis of bmp2-null mouse embryos

    PMID:10770922 PMID:11087629

    Open questions at the time
    • Smad-binding element in Tbx2 enhancer not yet identified
    • Relative contribution of Mitf vs. BMP2 in melanocytes unclear
  4. 2002 High

    Defining TBX2's cardiac patterning role: TBX2 cooperates with Nkx2.5 to repress ANF in atrioventricular canal myocardium, and domain analysis revealed both N-terminal and C-terminal repression domains, establishing the structural basis for context-dependent repression.

    Evidence Transgenic and in vivo mutagenesis of TBE/NKE elements; GAL4-deletion analysis of repression domains

    PMID:11867218 PMID:12023302

    Open questions at the time
    • Corepressor identity for cardiac targets unknown
    • Crystal structure of TBX2 repression domains not available
  5. 2004 High

    Identifying HDAC1 as a TBX2-recruited corepressor and expanding target gene repertoire: TBX2 directly binds p21WAF1 and Cx43 promoters and recruits HDAC1 to mediate repression, providing the first chromatin-modifying mechanism for TBX2-dependent silencing.

    Evidence ChIP for TBX2 and HDAC1 at the p21 promoter; siRNA knockdown; in vitro binding and mutagenesis of Cx43 T-box sites

    PMID:14996726 PMID:15354864 PMID:15781639

    Open questions at the time
    • Whether HDAC1 recruitment is universal across all TBX2 targets not tested
    • Structural basis of TBX2-HDAC1 interaction unknown
  6. 2004 High

    In vivo requirement for TBX2 in cardiac chamber patterning: Tbx2-null and Tbx2-overexpressing mice demonstrated that TBX2 is both necessary and sufficient to suppress chamber myocardium gene expression in the AVC, establishing its role as a binary cell-fate switch in heart morphogenesis.

    Evidence Targeted Tbx2 knockout and transgenic overexpression in mice with marker gene analysis

    PMID:15042700 PMID:15459098

    Open questions at the time
    • Redundancy with Tbx3 not yet quantified
    • Direct chromatin targets in AVC not genome-wide mapped
  7. 2007 High

    Post-translational regulation resolved: p38 MAPK phosphorylates TBX2 at S336/S623/S675 upon UV stress, stabilizing the protein and enhancing nuclear accumulation and p21 repressor activity—explaining how stress signals modulate TBX2 function.

    Evidence In vitro kinase assays; phospho-site mutagenesis; immunofluorescence; reporter assays

    PMID:18025091

    Open questions at the time
    • Other kinases that target TBX2 not surveyed
    • Phosphorylation effects on non-p21 targets not examined
  8. 2009 High

    Tbx20 restricts Tbx2 expression by a non-canonical mechanism: Tbx20 sequesters Smad1/5 away from Smad4, attenuating BMP-dependent activation of the Tbx2 AVC enhancer—resolving how chamber myocardium excludes Tbx2.

    Evidence Single and double knockout embryos; identification of BMP/Smad-dependent Tbx2 enhancer; Smad co-immunoprecipitation

    PMID:19661464

    Open questions at the time
    • Whether Tbx20 regulation of Tbx2 operates in non-cardiac tissues unknown
    • Direct Smad4-enhancer binding not shown by ChIP
  9. 2010 High

    Rb1 interaction enhances TBX2 function: TBX2 specifically binds hypophosphorylated Rb1 (not p107/p130) via a C-terminal domain, augmenting DNA binding and expanding target gene selectivity, linking TBX2 repression to the cell-cycle machinery.

    Evidence Co-immunoprecipitation; domain mapping; microarray with inducible dominant-negative TBX2 carrying Rb1-interaction domain mutation

    PMID:20534814

    Open questions at the time
    • Structural basis of TBX2-Rb1 interaction not resolved
    • Whether Rb1 is required for TBX2 function at all targets not determined
  10. 2011 High

    Functional consequences of cardiac Tbx2 loss defined at the electrophysiological level: myocardium-specific Tbx2 deletion causes accessory pathway formation (Wolff-Parkinson-White-like phenotype) with ectopic Cx40/Cx43/Scn5a expression, establishing TBX2 as essential for annulus fibrosus integrity and prevention of ventricular preexcitation.

    Evidence Conditional myocardium-specific knockout; electrophysiological recordings; immunohistochemistry

    PMID:21266775

    Open questions at the time
    • Whether human WPW cases involve TBX2 mutations not established
    • Relative contribution of Cx40 vs. Cx43 derepression to accessory pathway conduction not parsed
  11. 2011 High

    PML-TBX2 autoregulatory loop in senescence: PML represses TBX2 transcription via a p130/E2F4 complex, while TBX2 protein antagonizes PML's pro-senescence function through direct binding, establishing a feedback circuit governing cellular senescence.

    Evidence ChIP at TBX2 promoter; co-immunoprecipitation of PML-TBX2; knockdown experiments

    PMID:22002537

    Open questions at the time
    • In vivo significance of PML-TBX2 loop in tumor suppression not tested
    • Whether TBX2 disrupts PML nuclear bodies not examined
  12. 2013 High

    TBX2 controls organ growth by direct repression of CDK inhibitors: ChIP demonstrated TBX2 occupancy at Cdkn1a/Cdkn1b loci in lung mesenchyme, and genetic deletion of both CDK inhibitors rescued lung hypoplasia of Tbx2-null mice, proving these are the critical proliferation targets.

    Evidence Conditional knockout; double Cdkn1a/Cdkn1b genetic rescue; ChIP in lung tissue

    PMID:23341776

    Open questions at the time
    • Whether additional Tbx2 targets contribute to lung growth not excluded
    • Tbx2 targets in lung epithelium not addressed
  13. 2013 High

    TBX2 terminates the Shh/Fgf signaling loop in limb development: direct repression of Grem1 by TBX2 in posterior limb mesenchyme times the cessation of digit-forming signals, with loss causing polydactyly and gain causing premature loop termination.

    Evidence Conditional Tbx2 knockout and overexpression in mouse limbs; ChIP at Grem1 locus; digit phenotype analysis

    PMID:23633963

    Open questions at the time
    • Whether TBX2 and TBX3 have distinct Grem1-regulatory roles not resolved
    • Mechanism by which TBX2 selectively targets posterior mesenchyme unclear
  14. 2019 High

    A second corepressor mechanism elucidated: TBX2 recruits the HP1/KAP1/G9A/EZH2 complex via an N-terminal HP1-binding motif to establish H3K9me3 at target promoters, revealing a heterochromatin-based silencing pathway distinct from HDAC1 recruitment.

    Evidence Co-immunoprecipitation; HP1-binding motif mutagenesis; ChIP for H3K9me3 and complex components; siRNA knockdown

    PMID:31253870

    Open questions at the time
    • Which targets use HP1 versus HDAC1 pathway not globally defined
    • Whether both pathways operate simultaneously at the same locus unknown
  15. 2022 High

    TBX2 identified as the master binary switch for cochlear hair cell fate: ablation converts inner hair cells to outer hair cells and ectopic expression converts outer to inner, demonstrating sufficiency and necessity for inner hair cell identity—a previously unresolved question in auditory biology.

    Evidence Conditional knockout and ectopic expression in hair cells; epistasis with Insm1; IHC/OHC marker profiling

    PMID:35508658 PMID:36494345

    Open questions at the time
    • Direct transcriptional targets that mediate IHC specification not genome-wide identified
    • Whether TBX2 maintains IHC identity in the adult cochlea not fully tested
    • Therapeutic potential for hearing restoration via TBX2 manipulation not validated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) the genome-wide partitioning of HDAC1- versus HP1/EZH2-dependent repression across TBX2 target genes; (2) a structural model of TBX2 bound to DNA and corepressor complexes; (3) whether TBX2 functions as a transcriptional activator at select loci in vivo (as suggested for WNT3A and Tgfb2) or only indirectly; (4) the full repertoire of post-translational modifications beyond p38-mediated phosphorylation.
  • No crystal/cryo-EM structure of TBX2
  • Genome-wide corepressor usage not mapped
  • Activator function not confirmed by ChIP for activating marks

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 5 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 2 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-1266738 Developmental Biology 8 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 5 R-HSA-1640170 Cell Cycle 5 R-HSA-4839726 Chromatin organization 2
Partners
CBX5HDAC1MSX1MYOD1NKX2-5PMLRB1

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 TBX2 represses the Cdkn2a (p19ARF) promoter and attenuates E2F1, Myc, and HRAS-mediated induction of p19ARF, thereby bypassing cellular senescence and enabling immortalization. Genetic senescence bypass screen in Bmi1-deficient fibroblasts; promoter repression assays; transfection studies Nature genetics High 11062467
2002 TBX2 forms a complex with Nkx2.5 on the ANF promoter T-box binding element (TBE)-NK2 homeobox element (NKE) to cooperatively repress ANF gene expression in the atrioventricular canal myocardium. Transgenic analysis; in vivo mutagenesis of TBE and NKE elements; cotransfection/reporter assays; protein-protein interaction studies Genes & development High 12023302
2004 Tbx2 is required to repress chamber myocardium-specific genes (Nppa, Cx40, Cx43, Chisel) in the atrioventricular canal; transgenic overexpression of Tbx2 in prechamber myocardium completely blocks chamber formation and suppresses chamber-specific gene expression. Targeted mutagenesis (Tbx2 null mice); transgenic overexpression; molecular analysis of marker gene expression Developmental dynamics High 15042700 15459098
2002 TBX2 and TBX3 specifically bind a variant T-site (13/20 nucleotide match to consensus) in the human p14ARF promoter to repress its transcription; both the core T-box DNA-binding domain and a C-terminal conserved repression domain are required for p14ARF repression. Mutant analysis of promoter T-site; deletion/domain mutagenesis; transfection reporter assays The Journal of biological chemistry High 12000749
2004 Tbx2 directly binds and represses the p21(WAF1) promoter in vitro and in vivo; siRNA-mediated knockdown of Tbx2 robustly activates p21 expression. Tbx2 targets histone deacetylase 1 (HDAC1) to the p21 initiator to mediate repression. In vitro DNA-binding assays; transfection reporter assays; chromatin immunoprecipitation (ChIP); siRNA knockdown; inducible dominant-negative Tbx2 Cancer research High 14996726 15781639
1998 TBX2 acts as a transcriptional repressor by binding the MSEu and MSEi elements of the TRP-1 promoter; mutations in these elements that abolish TBX2 binding derepress TRP-1 promoter activity in melanocytes and melanoma cells. A high-affinity consensus Tbx2-binding site can constitutively repress a heterologous promoter. Electrophoretic mobility shift assays; cotransfection reporter assays; site-directed mutagenesis of promoter elements Molecular and cellular biology High 9710594
2000 TBX2 binds a palindromic T-oligonucleotide as a monomer (unlike Xbra which binds as a dimer) and represses transcription from a chimeric reporter, whereas Xbra activates the same promoter, demonstrating distinct DNA-binding stoichiometry and transcriptional modulation properties. In vitro DNA binding assays; cotransfection reporter assays; antibody supershift assays Gene High 11111039
2002 Murine Tbx2 contains two transcriptional repression domains: a C-terminal domain conserved with Tbx3/ET, and a novel N-terminal domain (amino-terminal to the T-box); the T-box itself can weakly activate transcription in a promoter-context-dependent manner. Deletion analysis linked to GAL4 DNA-binding domain; cotransfection reporter assays Gene Medium 11867218
2000 The Tbx2 promoter contains a full consensus Mitf (microphthalmia-associated transcription factor) recognition E-box element; Mitf binds the Tbx2 promoter in vitro and activates Tbx2 expression in vivo in an E-box-dependent manner, placing Tbx2 as a direct transcriptional target of Mitf in the melanocyte lineage. Promoter sequencing; in vitro binding (EMSA); in vivo transfection; E-box mutagenesis The Journal of biological chemistry High 10770922
2000 BMP2 signaling induces Tbx2 (and Tbx3) expression in non-cardiogenic embryonic tissue; the BMP antagonist Noggin downregulates Tbx2 gene activity; Tbx2 expression is absent in bmp2 null mouse embryos, placing Tbx2 downstream of BMP2 signaling in early cardiogenesis. BMP2 bead application to chick embryos; Noggin treatment; analysis of bmp2 null mouse embryos Developmental biology High 11087629
2006 Tbx2 protein levels are cell-cycle regulated: low in G1, rising through S-phase, persisting through G2, then dramatically reduced at mitosis onset. In S-phase, Tbx2 localizes to a subset of late replication foci and to small subnuclear DNA-associated foci distinct from telomeres, PML or Cajal bodies. Cell cycle synchronization; Western blotting; immunofluorescence; colocalization studies Experimental cell research Medium 16730707
2007 UV irradiation induces p38 MAPK-mediated phosphorylation of Tbx2 at serine residues 336, 623, and 675; this phosphorylation increases Tbx2 protein levels, drives nuclear localization, and enhances Tbx2-mediated repression of the p21 promoter. In vitro kinase assays; site-directed mutagenesis; Western blotting; immunofluorescence; reporter assays The Journal of biological chemistry High 18025091
2010 Tbx2 specifically associates with active hypophosphorylated retinoblastoma protein (Rb1), but not with p107 or p130; this interaction maps to a domain carboxy-terminal to the T-box, enhances Tbx2 DNA binding and transcriptional repression, and modulates Tbx2 target gene selectivity including cell cycle control genes. Co-immunoprecipitation; domain mapping; microarray analysis; inducible dominant-negative Tbx2 with Rb1-interaction domain mutation Molecular biology of the cell High 20534814
2009 Tbx20 directly attenuates BMP/Smad-dependent transcriptional activation of Tbx2 by binding Smad1 and Smad5 and sequestering them from Smad4, independently of Tbx20 DNA binding. A BMP/Smad-dependent Tbx2 enhancer confers AVC-restricted expression and Tbx20-dependent chamber suppression of Tbx2. Single and double knockout embryo analysis; identification of Tbx2 enhancer; transfection and localization studies; Smad binding assays Circulation research High 19661464
2011 Tbx2 and Tbx3 function redundantly to maintain AVC myocardium phenotype; ChIP-sequencing of Tbx3 reveals direct interaction with and repression of chamber myocardial genes; Tbx2/3 trigger atrioventricular cushion development through a regulatory feed-forward loop with Bmp2. Knockout and inducible overexpression mouse models; expression profiling; ChIP-sequencing Cellular and molecular life sciences High 22130515
2013 Tbx2 directly binds to the Cdkn1a (p21) and Cdkn1b (p27) loci in vivo in lung mesenchyme (ChIP); loss of Tbx2 causes lung hypoplasia with increased p21/p27 expression, and combined deletion of Cdkn1a and Cdkn1b largely rescues the lung growth deficit of Tbx2-deficient mice. Conditional knockout mice; genetic rescue (double Cdkn1a/Cdkn1b knockout); ChIP; gene expression analysis PLoS genetics High 23341776
2013 Tbx2 directly represses Grem1 in the posterior limb mesenchyme (by binding T-box elements in the Grem1 locus), thereby terminating the Shh/Fgf4 signaling loop; Tbx2-deficient hindlimbs show prolonged Shh/Fgf4 signaling and digit duplication, while overexpression causes premature loop termination. Tbx2 conditional knockout and overexpression in mice; ChIP; in vivo reporter assays; digit phenotype analysis PLoS genetics High 23633963
2016 Tbx2 and Tbx3 act downstream of epithelially derived Shh signaling in lung mesenchyme to maintain canonical Wnt signaling, in part by directly repressing the Wnt antagonists Frzb and Shisa3 (shown by ChIP), and thereby promote mesenchymal proliferation. Conditional double mutant mice; genetic rescue; ChIP; expression profiling Developmental cell High 27720610
2011 Genetic lineage tracing using Tbx2Cre shows that Tbx2+ primary myocardium of the AVC gives rise to the atrioventricular node; in Tbx2-deficient embryos, the AVC prematurely differentiates to chamber myocardium and proliferates at increased rates, demonstrating that Tbx2 temporally suppresses both differentiation and proliferation of primary myocardial cells. Genetic lineage tracing (Tbx2Cre knock-in); Tbx2-deficient embryo analysis; proliferation and marker analysis Circulation research High 19423846
2011 Myocardium-specific inactivation of Tbx2 leads to formation of fast-conducting accessory pathways (Wolff-Parkinson-White-like), malformation of the annulus fibrosus, and ventricular preexcitation; the accessory pathways ectopically express fast-conduction proteins Cx40, Cx43, and Scn5a, establishing that Tbx2 is required for proper atrioventricular myocardial patterning to prevent accessory pathway formation. Conditional myocardium-specific Tbx2 knockout; electrophysiological recordings; immunohistochemistry for gap junction proteins The Journal of clinical investigation High 21266775
2004 Tbx2 represses Connexin43 (Cx43) promoter activity by directly binding two TCACAC T-box consensus sites in the Cx43 promoter; antisense-mediated downregulation of Tbx2 in osteosarcoma cells de-represses endogenous Cx43 expression and increases functional gap junction communication. In vitro binding assays; cotransfection reporter assays; promoter mutagenesis; antisense stable transfection; transgenic mouse analysis Calcified tissue international High 15354864
2012 TBX2 directly represses E-cadherin transcription (shown by ChIP and reporter assays) and induces epithelial-mesenchymal transition (EMT); ectopic TBX2 in normal mammary epithelial cells causes loss of epithelial markers and gain of mesenchymal markers, increased invasion, and lung metastasis in xenografts. Ectopic TBX2 expression; TBX2 knockdown; ChIP; reporter assays; xenograft mouse model; EMT marker analysis PloS one High 22844464
2019 TBX2 interacts with Heterochromatin Protein 1 (HP1) through a conserved HP1-binding motif in its N-terminus; this recruits KAP1, DNMT3B, and histone methyltransferase complex components (G9A, EZH2, SUZ12) to EGR1-targeted promoters (e.g., NDRG1), establishing H3K9me3 repressive marks. Mutation of the TBX2 HP1-binding domain abrogates this interaction and relieves target gene repression. Co-immunoprecipitation; HP1-binding motif mutagenesis; ChIP for H3K9me3 and complex components; siRNA knockdown; reporter assays Oncogene High 31253870
2014 TBX2 directly represses the PTEN tumor suppressor promoter by binding it and recruiting HDAC1 in rhabdomyosarcoma and skeletal muscle cells; TBX2 depletion upregulates PTEN and reduces phospho-AKT, placing TBX2 in the PTEN/PI3K/AKT pathway. ChIP; HDAC1 recruitment assay; TBX2 knockdown/dominant-negative; Western blotting for phospho-AKT; xenograft tumor assay Oncogene High 26686089
2014 TBX2 interacts with myogenic regulatory factors MyoD and myogenin and inhibits their transcriptional activity; TBX2 recruits HDAC1 to muscle-specific gene promoters to repress expression, blocking differentiation in rhabdomyosarcoma cells. Co-immunoprecipitation of TBX2 with MyoD/myogenin; ChIP for HDAC1; gene expression analysis; TBX2 depletion/dominant-negative; xenograft assay International journal of cancer High 24470334
2011 PML tumor suppressor directly represses TBX2 transcription through a p130/E2F4 repressor complex at the TBX2 promoter in senescence; conversely, elevated TBX2 antagonizes PML pro-senescence function through direct protein-protein interaction with PML, establishing an autoregulatory loop. Gene expression profiling; ChIP; promoter reporter assays; PML-TBX2 co-immunoprecipitation; TBX2 knockdown/depletion The EMBO journal High 22002537
2012 Retinoic acid (RA) directly downregulates Tbx2 expression through a functional retinoic acid response element (RARE) in the Tbx2 promoter; Tbx2 in turn activates Tgfb2 expression in the outflow tract, and the Tbx2-Tgfβ2 cascade is required for epithelial-mesenchymal transition in outflow tract cushion development. Identification of RARE in Tbx2 promoter; RA treatment of mouse embryos; Tgfb2 rescue in organ culture; gene expression analysis Development Medium 22186728
2014 TGF-β1 signaling upregulates TBX3, which then transcriptionally represses TBX2 expression, and this TBX2 downregulation mediates part of the anti-proliferative function of the TGF-β1-TBX3 axis. TGF-β1 treatment; TBX3 knockdown/overexpression; TBX2 promoter reporter assays; proliferation assays The Journal of biological chemistry Medium 25371204
2013 TBX2 co-represses CST6 (Cystatin 6) together with EGR1; this relieves Legumain (LGMN) from inhibition, sustaining breast cancer proliferation. CST6 expression in TBX2-expressing breast cancer cells induces apoptosis specifically through its LGMN-inhibitory domain. TBX2 knockdown; ectopic CST6 expression; CST6 domain mutagenesis; siRNA knockdown of LGMN; LGMN activity assays Oncotarget Medium 24742492
2017 TBX2 acts in trans to promote transcription of the canonical WNT3A promoter in prostate cancer cells; blocking endogenous TBX2 reduces WNT3A expression, invasion, and bone metastasis, and genetic rescue of WNT3A partially restores TBX2-induced metastatic capability. Dominant-negative TBX2 construct; WNT3A promoter reporter assays; xenograft and intratibial mouse models; WNT3A rescue experiment; WNT3A-neutralizing antibodies Cancer research Medium 28108510
2022 Tbx2 is a master regulator of inner vs. outer hair cell (IHC vs. OHC) fate in the cochlea: ablation of Tbx2 in embryonic IHCs causes complete transdifferentiation into OHCs; ectopic Tbx2 in OHCs causes their transdifferentiation into IHCs. Tbx2 is epistatic to Insm1: in the absence of both, only OHCs form, indicating TBX2 is necessary for INSM1-deficient OHC-to-IHC transdifferentiation. Conditional knockout (hair cell-specific Cre); ectopic overexpression in OHCs; epistasis double knockout; marker analysis for IHC/OHC identity Nature High 35508658
2022 TBX2 specifies the inner compartment (IHCs and inner supporting cells) of the cochlear sensory epithelium; conditional deletion converts IHCs to OHCs (repressing IHC genes, inducing OHC genes including Ikzf2), and misexpression converts OHCs to IHCs. Coupled with transient Atoh1, Tbx2 can reprogram non-sensory supporting cells into IHC-like cells. Conditional deletion (hair cell- and progenitor-specific Cre); conditional misexpression; transdifferentiation/reprogramming assays; IHC/OHC marker profiling Nature communications High 36494345
2021 TBX2 acts downstream of otocyst Tbx2/Tbx3-mediated repression of FGF signaling to restrict neurogenesis to the anterior-ventral otocyst; conditional Tbx2 ablation from the otocyst causes cochlear hypoplasia and posterior-ventral expansion of the neurogenic domain. Conditional knockout (otocyst-specific); expression analyses; FGF signaling readouts Development Medium 33795231
2018 TBX2 p.R20Q and p.R305H variants identified in patients with a DiGeorge-like syndrome show reduced transcriptional repressor activity and reduced protein levels in vitro; heterologous overexpression in Drosophila demonstrates both variants are partial loss-of-function alleles. In vitro transcriptional repression assays; protein level analysis; Drosophila overexpression assay Human molecular genetics Medium 29726930
2013 Tbx2 and Msx1 can physically interact in mouse C3H10T1/2 cells; Tbx2 represses Bmp4 expression in dental mesenchyme, and reducing Tbx2 dosage (Msx1-/-;Tbx2+/- compound mutants) partially rescues the Msx1-/- bud-stage arrest and restores mesenchymal Bmp4 expression. Co-immunoprecipitation of Tbx2 and Msx1; Tbx2 knockdown in C3H10T1/2 cells; Bmp4 expression analysis; genetic compound mutant rescue Development High 23720046
2018 TBX2 and TBX3 act downstream of canonical WNT signaling in the ureteric mesenchyme; ChIP reveals TBX2/TBX3 directly repress Dkk2, Shisa2 (WNT antagonists), Bmper (BMP antagonist), and Cxcl12; loss of TBX2/TBX3 disrupts Foxf1 and BMP4 signaling, reducing smooth muscle cell differentiation. Conditional double knockout mice; ChIP; transcriptional profiling; smooth muscle differentiation analysis Development High 30478225
2013 TBX2 interacts with HPV16 minor capsid protein L2, confirmed by co-immunoprecipitation and immunofluorescence; TBX2 (and TBX3) repress transcription from the HPV long control region (LCR) in reporter assays, and this repression is enhanced by L2; TBX2 binding to the HPV LCR was confirmed by ChIP. Yeast two-hybrid screening; co-immunoprecipitation; immunofluorescence; promoter reporter assays; ChIP Journal of virology Medium 23388722
2018 TBX2 is a constituent of the core regulatory circuitry in neuroblastoma; TBX2 drives proliferation through activation of FOXM1 target genes that are normally repressed by the p21-DREAM complex; combined TBX2/MYCN knockdown enforces cell growth arrest, indicating TBX2 enhances MYCN-sustained FOXM1 target activation. Epigenomic super-enhancer analysis; TBX2/MYCN knockdown; cell proliferation assays; gene expression profiling Nature communications Medium 30451831
2021 TBX2 binds the promoter of miR-200c-3p and represses its expression; repression of miR-200c-3p increases SOX2 and N-MYC levels; this TBX2/miR-200c-3p/SOX2/N-MYC axis promotes neuroendocrine prostate cancer transdifferentiation both intracellularly and via exosome-mediated intercellular signaling. Promoter binding assay; miR profiling; rescue with miR-200c-3p re-expression; exosome co-culture experiments Cancers Medium 34638504

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19(ARF)) and is amplified in a subset of human breast cancers. Nature genetics 318 11062467
2002 Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation. Genes & development 292 12023302
2004 Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development. Development (Cambridge, England) 230 15459098
2004 T-box transcription factor Tbx2 represses differentiation and formation of the cardiac chambers. Developmental dynamics : an official publication of the American Association of Anatomists 205 15042700
2005 Tbx2 is overexpressed and plays an important role in maintaining proliferation and suppression of senescence in melanomas. Cancer research 183 15781639
2000 Expression of chick Tbx-2, Tbx-3, and Tbx-5 genes during early heart development: evidence for BMP2 induction of Tbx2. Developmental biology 170 11087629
2005 Tbx20 is essential for cardiac chamber differentiation and repression of Tbx2. Development (Cambridge, England) 160 15901664
1998 Brachyury-related transcription factor Tbx2 and repression of the melanocyte-specific TRP-1 promoter. Molecular and cellular biology 149 9710594
1998 Involvement of T-box genes Tbx2-Tbx5 in vertebrate limb specification and development. Development (Cambridge, England) 144 9609833
1998 Expression of T-box genes Tbx2-Tbx5 during chick organogenesis. Mechanisms of development 140 9651516
2002 The T-box repressors TBX2 and TBX3 specifically regulate the tumor suppressor gene p14ARF via a variant T-site in the initiator. The Journal of biological chemistry 135 12000749
2004 Tbx2 directly represses the expression of the p21(WAF1) cyclin-dependent kinase inhibitor. Cancer research 133 14996726
2009 The Tbx2+ primary myocardium of the atrioventricular canal forms the atrioventricular node and the base of the left ventricle. Circulation research 131 19423846
2011 Tbx2 and Tbx3 induce atrioventricular myocardial development and endocardial cushion formation. Cellular and molecular life sciences : CMLS 114 22130515
2006 Regional morphogenesis in the hypothalamus: a BMP-Tbx2 pathway coordinates fate and proliferation through Shh downregulation. Developmental cell 111 17141161
2010 The T-box transcription factor Tbx2: its role in development and possible implication in cancer. IUBMB life 105 19960541
2007 Hesr1 and Hesr2 regulate atrioventricular boundary formation in the developing heart through the repression of Tbx2. Development (Cambridge, England) 103 17259303
2002 FGF signaling regulates expression of Tbx2, Erm, Pea3, and Pax3 in the early nasal region. Developmental biology 102 12086464
2009 Tbx20 interacts with smads to confine tbx2 expression to the atrioventricular canal. Circulation research 95 19661464
2000 The gene encoding the T-box factor Tbx2 is a target for the microphthalmia-associated transcription factor in melanocytes. The Journal of biological chemistry 88 10770922
2018 TBX2 is a neuroblastoma core regulatory circuitry component enhancing MYCN/FOXM1 reactivation of DREAM targets. Nature communications 84 30451831
2007 Tbx2 and Tbx3 regulate the dynamics of cell proliferation during heart remodeling. PloS one 84 17460765
2004 The role of Tbx2 and Tbx3 in mammary development and tumorigenesis. Journal of mammary gland biology and neoplasia 80 15300007
2010 The Highly Homologous T-Box Transcription Factors, TBX2 and TBX3, Have Distinct Roles in the Oncogenic Process. Genes & cancer 76 21779450
2000 Differential DNA binding and transcription modulation by three T-box proteins, T, TBX1 and TBX2. Gene 75 11111039
2011 Defective Tbx2-dependent patterning of the atrioventricular canal myocardium causes accessory pathway formation in mice. The Journal of clinical investigation 73 21266775
2005 Tbx3, the ulnar-mammary syndrome gene, and Tbx2 interact in mammary gland development through a p19Arf/p53-independent pathway. Developmental dynamics : an official publication of the American Association of Anatomists 70 16222716
2002 TBX2 is preferentially amplified in BRCA1- and BRCA2-related breast tumors. Cancer research 69 12097257
2000 Conserved and divergent expression of T-box genes Tbx2-Tbx5 in Xenopus. Mechanisms of development 68 10704879
2022 Tbx2 is a master regulator of inner versus outer hair cell differentiation. Nature 64 35508658
2013 Tbx2 controls lung growth by direct repression of the cell cycle inhibitor genes Cdkn1a and Cdkn1b. PLoS genetics 64 23341776
2011 Wnt signaling regulates atrioventricular canal formation upstream of BMP and Tbx2. Birth defects research. Part A, Clinical and molecular teratology 61 21567896
2011 Identification of a Tbx1/Tbx2/Tbx3 genetic pathway governing pharyngeal and arterial pole morphogenesis. Human molecular genetics 61 22116936
1995 Cloning and mapping of a human gene (TBX2) sharing a highly conserved protein motif with the Drosophila omb gene. Genomics 60 8530034
2018 Functional variants in TBX2 are associated with a syndromic cardiovascular and skeletal developmental disorder. Human molecular genetics 59 29726930
2017 Bone Metastasis of Prostate Cancer Can Be Therapeutically Targeted at the TBX2-WNT Signaling Axis. Cancer research 59 28108510
2013 The T-box transcription factors TBX2 and TBX3 in mammary gland development and breast cancer. Journal of mammary gland biology and neoplasia 59 23624936
2016 Tbx2 and Tbx3 Act Downstream of Shh to Maintain Canonical Wnt Signaling during Branching Morphogenesis of the Murine Lung. Developmental cell 57 27720610
2002 Murine Tbx2 contains domains that activate and repress gene transcription. Gene 57 11867218
2011 Microdeletion of 17q22q23.2 encompassing TBX2 and TBX4 in a patient with congenital microcephaly, thyroid duct cyst, sensorineural hearing loss, and pulmonary hypertension. American journal of medical genetics. Part A 54 21271665
2010 TBX2 and TBX3: the special value for anticancer drug targets. Biochimica et biophysica acta 54 20624445
2006 The T-box factor TBX-2 and the SUMO conjugating enzyme UBC-9 are required for ABa-derived pharyngeal muscle in C. elegans. Developmental biology 54 16701625
2012 The T box transcription factor TBX2 promotes epithelial-mesenchymal transition and invasion of normal and malignant breast epithelial cells. PloS one 51 22844464
2013 Tbx2 terminates shh/fgf signaling in the developing mouse limb bud by direct repression of gremlin1. PLoS genetics 48 23633963
2008 Conservation of linkage and evolution of developmental function within the Tbx2/3/4/5 subfamily of T-box genes: implications for the origin of vertebrate limbs. Development genes and evolution 48 18815807
2010 Expression of PSCA, PIWIL1 and TBX2 and its correlation with HPV16 infection in formalin-fixed, paraffin-embedded cervical squamous cell carcinoma specimens. Archives of virology 45 20229117
2006 Characterization of a novel ectodermal signaling center regulating Tbx2 and Shh in the vertebrate limb. Developmental biology 45 17300775
2007 Ectopic Tbx2 expression results in polyploidy and cisplatin resistance. Oncogene 44 17700536
2004 ERBB2, TBX2, RPS6KB1, and MYC alterations in breast tissues of BRCA1 and BRCA2 mutation carriers. Genes, chromosomes & cancer 42 15236312
2003 Coquillette, a sea urchin T-box gene of the Tbx2 subfamily, is expressed asymmetrically along the oral-aboral axis of the embryo and is involved in skeletogenesis. Mechanisms of development 42 12782273
2014 Stratification based on methylation of TBX2 and TBX3 into three molecular grades predicts progression in patients with pTa-bladder cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 41 25394776
2019 TBX2 interacts with heterochromatin protein 1 to recruit a novel repression complex to EGR1-targeted promoters to drive the proliferation of breast cancer cells. Oncogene 40 31253870
2012 Ectopic retinoic acid signaling affects outflow tract cushion development through suppression of the myocardial Tbx2-Tgfβ2 pathway. Development (Cambridge, England) 40 22186728
2014 The anti-proliferative function of the TGF-β1 signaling pathway involves the repression of the oncogenic TBX2 by its homologue TBX3. The Journal of biological chemistry 39 25371204
2006 Cell cycle regulation of the T-box transcription factor tbx2. Experimental cell research 39 16730707
1995 Identification, characterization, and localization to chromosome 17q21-22 of the human TBX2 homolog, member of a conserved developmental gene family. Mammalian genome : official journal of the International Mammalian Genome Society 39 8597636
2021 Regulation of otocyst patterning by Tbx2 and Tbx3 is required for inner ear morphogenesis in the mouse. Development (Cambridge, England) 38 33795231
2014 TBX2 represses CST6 resulting in uncontrolled legumain activity to sustain breast cancer proliferation: a novel cancer-selective target pathway with therapeutic opportunities. Oncotarget 38 24742492
2003 Distinct expression patterns of the two T-box homologues Brachyury and Tbx2/3 in the placozoan Trichoplax adhaerens. Development genes and evolution 38 13680223
2010 Expression of PSCA, PIWIL1, and TBX2 in endometrial adenocarcinoma. Onkologie 37 20502058
2007 UV-mediated regulation of the anti-senescence factor Tbx2. The Journal of biological chemistry 37 18025091
2006 Role of T-box gene tbx-2 for anterior foregut muscle development in C. elegans. Developmental biology 36 17005176
2009 Tbx2 misexpression impairs deployment of second heart field derived progenitor cells to the arterial pole of the embryonic heart. Developmental biology 35 19563797
2009 Expression and requirement of T-box transcription factors Tbx2 and Tbx3 during secondary palate development in the mouse. Developmental biology 35 19769959
2004 TBX2/TBX3 transcriptional factor homologue controls olfactory adaptation in Caenorhabditis elegans. Journal of neurobiology 35 14750151
2011 Physical and functional interaction between PML and TBX2 in the establishment of cellular senescence. The EMBO journal 33 22002537
2002 Conserved expression control and shared activity between cognate T-box genes Tbx2 and Tbx3 in connection with Sonic hedgehog signaling during Xenopus eye development. Development, growth & differentiation 33 12175361
2022 TBX2 specifies and maintains inner hair and supporting cell fate in the Organ of Corti. Nature communications 32 36494345
2015 TBX2 represses PTEN in rhabdomyosarcoma and skeletal muscle. Oncogene 32 26686089
2013 Tbx2/3 is an essential mediator within the Brachyury gene network during Ciona notochord development. Development (Cambridge, England) 32 23674602
2009 Loss of Tbx2 delays optic vesicle invagination leading to small optic cups. Developmental biology 32 19576202
2022 Development and transdifferentiation into inner hair cells require Tbx2. National science review 31 36687561
2008 Expression of Tbx2 and Tbx3 in the developing hypothalamic-pituitary axis. Gene expression patterns : GEP 31 18534921
2014 TBX2 blocks myogenesis and promotes proliferation in rhabdomyosarcoma cells. International journal of cancer 30 24470334
2013 Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud-to-cap stage transition in tooth development. Development (Cambridge, England) 29 23720046
2010 The retinoblastoma protein modulates Tbx2 functional specificity. Molecular biology of the cell 29 20534814
2004 Tbx2 represses expression of Connexin43 in osteoblastic-like cells. Calcified tissue international 29 15354864
2018 EGR1 interacts with TBX2 and functions as a tumor suppressor in rhabdomyosarcoma. Oncotarget 28 29719592
2018 TBX2 and TBX3 act downstream of canonical WNT signaling in patterning and differentiation of the mouse ureteric mesenchyme. Development (Cambridge, England) 28 30478225
2006 Developmental expression patterns of Tbx1, Tbx2, Tbx5, and Tbx20 in Xenopus tropicalis. Developmental dynamics : an official publication of the American Association of Anatomists 28 16477648
2013 A novel role for the anti-senescence factor TBX2 in DNA repair and cisplatin resistance. Cell death & disease 27 24113180
2011 Role of Tbx2 in defining the territory of the pronephric nephron. Development (Cambridge, England) 23 21205791
2013 The transcription factors TBX2 and TBX3 interact with human papillomavirus 16 (HPV16) L2 and repress the long control region of HPVs. Journal of virology 22 23388722
2009 Expression of TBX2 promotes anchorage-independent growth and survival in the p53-negative SW13 adrenocortical carcinoma. Cancer letters 22 19216023
2019 Epigenetic Suppression of the T-box Subfamily 2 (TBX2) in Human Non-Small Cell Lung Cancer. International journal of molecular sciences 21 30866410
2013 Brachyury, Tbx2/3 and sall expression during embryogenesis of the indirectly developing polychaete Hydroides elegans. The International journal of developmental biology 21 23585355
1999 Expression of Xenopus T-box transcription factor, tbx2 in Xenopus embryo. Development genes and evolution 21 10552304
2012 TBX2 expression is regulated by PAX3 in the melanocyte lineage. Pigment cell & melanoma research 20 23020925
2011 Dynamic expression of Tbx2 subfamily genes in development of the mouse reproductive system. Developmental dynamics : an official publication of the American Association of Anatomists 20 22223620
2011 Heart chamber size in zebrafish is regulated redundantly by duplicated tbx2 genes. Developmental dynamics : an official publication of the American Association of Anatomists 19 21448936
2010 TBX2 gene duplication associated with complex heart defect and skeletal malformations. American journal of medical genetics. Part A 19 20635360
2021 TBX2 Drives Neuroendocrine Prostate Cancer through Exosome-Mediated Repression of miR-200c-3p. Cancers 18 34638504
2018 Identification of TBX2 and TBX3 variants in patients with conotruncal heart defects by target sequencing. Human genomics 18 30223900
2018 TBX2 overexpression promotes proliferation and invasion through epithelial-mesenchymal transition and ERK signaling pathway. Experimental and therapeutic medicine 18 30651856
2016 Tbx2 regulates anterior neural specification by repressing FGF signaling pathway. Developmental biology 18 27913219
2014 The orthologous Tbx transcription factors Omb and TBX2 induce epithelial cell migration and extrusion in vivo without involvement of matrix metalloproteinases. Oncotarget 18 25344916
2005 T-box and homeobox genes from the ctenophore Pleurobrachia pileus: comparison of Brachyury, Tbx2/3 and Tlx in basal metazoans and bilaterians. FEBS letters 18 16122738
2017 TBX2 over-expression promotes nasopharyngeal cancer cell proliferation and invasion. Oncotarget 17 28881763
2010 Generation of mice with a conditional null allele for Tbx2. Genesis (New York, N.Y. : 2000) 17 20095052
2005 Expression pattern of the Brachyury and Tbx2 homologues from the sponge Suberites domuncula. Biology of the cell 17 15850455