| 2001 |
TGIF2 recruits histone deacetylase 1 (HDAC1) to repress transcription. Unlike TGIF1, TGIF2 cannot interact with the corepressor CtBP. TGIF2 binds DNA via its homeodomain at TGIF binding sites and represses transcription. TGIF2 also interacts directly with TGFβ-activated Smads to repress TGFβ-responsive transcription. |
Co-immunoprecipitation, reporter gene assays, DNA-binding assays |
The Journal of biological chemistry |
High |
11427533
|
| 2000 |
TGIF2 protein contains a putative nuclear localization signal and translocates to the nucleus, as confirmed by transfection of epitope-tagged cDNA. TGIF2 is a TALE-superclass homeodomain protein. |
Subcellular localization by transfection and imaging of epitope-tagged protein |
Biochemical and biophysical research communications |
Medium |
11006116
|
| 2006 |
TGIF2 interacts with the transcriptional corepressor mSin3, providing an additional repression mechanism. Both full-length and a shorter splice variant (lacking 39 amino acids) of mouse Tgif2 are functional transcriptional repressors that can repress TGFβ-dependent and -independent transcription. The Tgif2 gene contains a retained intron within its coding sequence. |
Co-immunoprecipitation, reporter gene assays, RT-PCR splice variant analysis |
BMC molecular biology |
Medium |
16436215
|
| 2010 |
Tgif1 and Tgif2 together are required for gastrulation; double-null mouse embryos fail to gastrulate. Genetic reduction of Nodal dosage partially rescues the gastrulation and left-right asymmetry defects in embryos lacking all Tgif function, establishing that Tgifs limit the transcriptional response to Nodal/TGFβ signaling during early embryogenesis. Extra-embryonic Tgif function (single wild-type allele of Tgif1 in extra-embryonic tissue) is sufficient to allow gastrulation. |
Conditional knockout mouse genetics, genetic epistasis (Nodal dosage reduction), embryo phenotype analysis |
Development (Cambridge, England) |
High |
20040491
|
| 2016 |
Loss of both Tgif1 and Tgif2 in mice results in holoprosencephaly and defects in left-right asymmetry. The combination of Tgif1 and Tgif2 mutations increases severity and penetrance of posterior axial transformation phenotype. Tgif1/Tgif2 regulate axial patterning and Hoxc6 expression, and reduced TGIF function sensitizes embryos to retinoic acid effects. |
Mouse knockout genetics, embryo phenotypic analysis, gene expression analysis |
PloS one |
Medium |
27187787
|
| 2017 |
TGIF1 directly binds to a conserved consensus TGIF site 5' of the Evi5l gene and represses its expression. Loss of both Tgif1 and Tgif2 increases Evi5l (a RabGAP) expression, which reduces primary cilia number. Reducing Evi5l expression in double-null MEFs partially restores cilium numbers and Shh pathway transcriptional response, placing Tgif1/2 upstream of Evi5l in ciliogenesis regulation. |
Chromatin immunoprecipitation, transcriptome profiling, shRNA knockdown, primary MEF analysis, Shh pathway reporter assays |
Molecular and cellular biology |
High |
27956704
|
| 2017 |
TGIF2 acts as a developmental regulator sufficient to drive liver-to-pancreas fate conversion. Expression of Tgif2 in hepatocytes causes transcriptional remodelling that represses hepatic identity and induces a pancreatic progenitor-like phenotype both ex vivo and in vivo in adult mouse hepatocytes. |
Forced expression in hepatocytes (ex vivo and in vivo mouse), transcriptome profiling, lineage marker analysis |
Nature communications |
High |
28193997
|
| 2019 |
EGFR/RAS/ERK signaling phosphorylates TGIF2 and increases its protein stability. Phosphorylation of TGIF2 is required for its pro-stemness functions in lung adenocarcinoma, as phosphorylation-deficient TGIF2 mutants lose these activities. TGIF2 binds the OCT4 promoter and promotes OCT4 expression. |
Phosphorylation-deficient mutant analysis, ChIP assay, xenograft mouse models, in vitro cell biology assays |
Signal transduction and targeted therapy |
Medium |
31871777
|
| 2018 |
Nuclear PKM2 promotes post-translational degradation of TGIF2 protein via the ubiquitin-proteasome system during EMT in oral squamous cell carcinoma cells. TGIF2 protein and mRNA expression were discordant in EMT-induced cells, and proteasome inhibition with MG132 blocked TGIF2 protein loss. |
Western blot mRNA/protein discordance analysis, proteasome inhibitor (MG132) rescue assay, PKM2 knockdown |
Oncotarget |
Medium |
30333907
|
| 2017 |
TGIF2 represses Smad pathway activity, and its restoration in miR-181a-overexpressing prostate cancer cells inhibits Smad2/3 phosphorylation, nuclear localization of Smad2/3, and EMT processes, confirming TGIF2 functions as a repressor of the Smad pathway in this context. |
TGIF2 overexpression rescue, Smad2/3 nuclear localization immunostaining, Western blot for EMT markers |
European review for medical and pharmacological sciences |
Low |
29164579
|
| 2022 |
TGIF2 forms a transcriptional complex with DDX17, SMAD3, and the JAG1 intracellular domain (JICD1) to increase SOX2 expression, driving oncogenic transformation and stemness in astrocytes. This was identified by proteomics, ChIP-seq, and transcriptome analysis. |
Co-immunoprecipitation/proteomics, ChIP-seq, transcriptome profiling |
Cell reports |
Medium |
36417870
|
| 2023 |
Phosphorylation of TGIF2 by EGFR/ERK signaling is required to recruit HDAC1 to the E-cadherin promoter, suppressing E-cadherin transcription and promoting EMT. Phosphorylation-deficient TGIF2 mutants fail to recruit HDAC1 and cannot promote migration/EMT. HDAC1 inhibition blocks TGIF2 phosphorylation-induced EMT. |
Co-immunoprecipitation, dual-luciferase reporter assay, ChIP assay, phosphorylation-deficient mutant analysis, xenograft mouse models |
BMC cancer |
Medium |
36647029
|
| 2020 |
TGIF2 directly binds to the FCMR gene promoter and represses FCMR expression, thereby promoting cervical cancer cell proliferation and metastasis. This was confirmed by luciferase assay, and rescue experiments showed simultaneous FCMR knockdown partially reversed the inhibition caused by TGIF2 knockdown. |
Luciferase reporter assay, ChIP (implied by promoter binding), shRNA knockdown, rescue experiments, xenograft mouse model |
European review for medical and pharmacological sciences |
Low |
32572908
|
| 2022 |
LSD1 histone demethylase binds the TGIF2 promoter and is associated with reduced H3K4me1 monomethylation at the TGIF2 locus, potentially mediating TGIF2 downregulation. Adenovirus-mediated TGIF2 overexpression activated the Wnt/β-catenin signaling pathway in mouse hippocampal neurons and suppressed neuronal apoptosis. |
ChIP-qPCR, adenovirus-mediated overexpression, gene set enrichment analysis, ENCODE database validation |
Brain and behavior |
Low |
35592894
|
| 2016 |
Tgif2 participates in photoreceptor cell fate determination in the early mouse retina: knockdown decreases rod photoreceptors and increases cones in retinal explants, while overexpression (conditional knock-in) causes abnormal cone nuclear localization in the outer nuclear layer without affecting cone function. |
shRNA knockdown in retinal explants, conditional knock-in mouse model, electroretinography, histological analysis |
Experimental eye research |
Medium |
27639517
|
| 2025 |
TGIF2 controls neural stem cell (NSC) fate maintenance by interacting with the SIN3A/HDAC repressor complex to suppress neuronal differentiation genes. TGIF2 is identified as the major regulator of neurogenic priming in cortical NSCs, restraining neuronal differentiation gene activation. This was demonstrated by in vitro and in vivo experiments in the mouse cerebral cortex. |
RNA-seq, ATAC-seq, Co-immunoprecipitation with SIN3A/HDAC complex, in vitro and in vivo overexpression/knockdown experiments in mouse NSCs |
bioRxivpreprint |
Medium |
bio_10.1101_2025.02.13.635953
|
| 2025 |
TGIF2 transcriptionally upregulates HMGB3 expression in esophageal squamous cell carcinoma, as demonstrated by luciferase reporter and ChIP assays. HMGB3 then activates TGF-β signaling through interaction with TLR3, promoting proliferation and metastasis. |
Luciferase reporter assay, ChIP assay, Co-immunoprecipitation, RNA sequencing |
Genes & diseases |
Medium |
41716633
|
| 2025 |
Smad2 cooperates with TGIF2 to co-regulate the SOX2 promoter in pancreatic cancer. TGIF2 promotes SOX2, Slug, CD44, and EGFR/MAPK signaling, and SOX2-driven transactivation of EGFR/MAPK promotes TGIF2 nuclear translocation, forming a positive feedback loop. TGIF2 nuclear translocation was demonstrated in vitro. |
ChIP assay (SOX2 promoter co-occupancy), Co-immunoprecipitation, subcellular fractionation/localization, in vivo xenograft |
International journal of biological sciences |
Medium |
39781447
|