| 2010 |
Tgif1 and Tgif2 act as transcriptional co-repressors that limit the response to Nodal signaling during gastrulation; genetic reduction of Nodal dose partially rescues gastrulation defects in Tgif1/Tgif2 double-null embryos, placing Tgifs upstream of Nodal-responsive transcription in early embryogenesis. |
Conditional knockout mouse genetics, genetic epistasis with Nodal dosage reduction |
Development (Cambridge, England) |
High |
20040491
|
| 2010 |
The E3 ubiquitin ligase substrate-recognition factor Fbxw7 targets TGIF1 for proteasomal degradation in a phosphorylation-dependent manner; inactivation of Fbxw7 leads to accumulation of phosphorylated TGIF1 and repression of TGFβ-dependent transcription, thereby attenuating TGFβ-regulated cell growth and migration. |
Co-immunoprecipitation, ubiquitination assays, cancer cell lines with Fbxw7 loss-of-function mutations, cell growth and migration assays |
Oncogene |
Medium |
20622901
|
| 2018 |
The TGIF1 homeodomain (HD) binds the TGACA DNA motif through both the HD core/major groove and the N-terminal arm/minor groove; additionally, the TGIF1-HD directly interacts with the MH1 domain of Smad proteins, and this HD-MH1 interaction partially occludes the DNA-binding site of the complex, providing a mechanism by which TGIF1 is released from promoters to actively repress Smad-induced TGFβ signaling. |
Crystal structure of TGIF1-HD bound to DNA, NMR, in vitro binding assays, functional reporter assays |
Nucleic acids research |
High |
30060237
|
| 2019 |
Tgif1 is a PTH target gene in osteoblasts; deletion of Tgif1 in osteoblasts/osteocytes impairs osteoblast differentiation and reduces bone formation, and also decreases bone resorption by increasing secretion of the osteoclast-inhibiting factor Semaphorin 3E (Sema3E). PTH failed to increase bone formation in Tgif1-deficient mice, identifying Tgif1 as an essential component of PTH anabolic action. |
Conditional knockout mice, bone histomorphometry, PTH treatment experiments, Sema3E secretion assays |
Nature communications |
High |
30902975
|
| 2013 |
Tgif1 regulates hematopoietic stem cell (HSC) quiescence and self-renewal; Tgif1-null bone marrow cells show greater self-renewal, reduced proliferation, and increased quiescence, whereas Tgif1 overexpression increases proliferation but reduces long-term survival in transplant assays, indicating Tgif1 suppresses stem cell self-renewal. |
CFU assays, competitive repopulation/serial transplantation in mice, BrdU labeling for quiescence |
Molecular and cellular biology |
High |
24100014
|
| 2015 |
Tgif1 directly represses core pluripotency factors (Oct4, Sox2, Nanog) in mouse embryonic stem cells independently of TGFβ/activin/nodal signaling; Tgif1 physically associates with Oct4, Nanog, and HDAC1/2, counterbalancing the autoregulatory amplification of core pluripotency factors. |
Co-immunoprecipitation, overexpression and knockdown in ESCs, reporter assays, treatment with activin/nodal pathway inhibitors |
Cell reports |
Medium |
26411691
|
| 2012 |
Primary MEFs lacking Tgif1 senesce prematurely, accumulate increased DNA damage, and are more sensitive to TGFβ-mediated growth inhibition; treatment with a TGFβ receptor kinase inhibitor rescues proliferation of Tgif1-null MEFs, demonstrating that elevated TGFβ signaling in the absence of Tgif1 contributes to premature senescence. |
Primary MEF culture, proliferation assays, senescence markers (SA-β-gal), DNA damage markers (γH2AX), TGFβ receptor kinase inhibitor treatment |
PloS one |
Medium |
22514746
|
| 2011 |
TGIF1 functions as a GnRH pulse-frequency-sensitive corepressor of FSHβ gene transcription; overexpression of binding- or phosphorylation-defective TGIF1 mutants fails to repress Fshb promoter activity, and TGIF1 occupies the FSHβ promoter in a cyclical manner after GnRH stimulation as shown by ChIP. |
Chromatin immunoprecipitation (ChIP), Fshb promoter reporter assays, siRNA knockdown, overexpression of TGIF1 mutants, GnRH pulse experiments |
Molecular endocrinology (Baltimore, Md.) |
Medium |
21659477
|
| 2017 |
TGIF1 binds to a conserved consensus TGIF site 5' of the Evi5l gene and represses its expression; loss of both Tgif1 and Tgif2 increases Evi5l expression, reduces primary cilia numbers in MEFs, and impairs the Shh transcriptional response; reducing Evi5l in double-null MEFs partially restores cilia numbers and Shh signaling. |
Transcriptome profiling, ChIP, Evi5l knockdown rescue experiments, cilia quantification by microscopy, Shh pathway reporter assays |
Molecular and cellular biology |
High |
27956704
|
| 2018 |
NMR structure of TGIF1-HD (TALE-type homeodomain) determined; holoprosencephaly-associated mutations P192A and R219C disrupt packing of helices α1 and α2 against α3, destabilize the HD structure, and reduce DNA-binding affinity by 23-fold and 10-fold respectively, as measured by isothermal titration calorimetry. |
NMR structure determination, circular dichroism, isothermal titration calorimetry, 1H-15N HSQC of P192A mutant |
Biochemical and biophysical research communications |
High |
29355528
|
| 2018 |
ZIC2 (an HPE-causative transcription factor) directly binds to Zic2-binding sites (ZBS) on the 5' flanking region of the Tgif1 gene and activates Tgif1 transcription, as demonstrated by ChIP and in vitro DNA binding assays; ZBS are required for Zic2-dependent transcriptional activation in reporter assays, linking two HPE-causative genes in a direct regulatory relationship. |
Chromatin immunoprecipitation (ChIP), in vitro DNA binding assays, reporter gene assays |
Scientific reports |
Medium |
29391420
|
| 2019 |
TGIF1 associates with Twist1 and inhibits Twist1 expression and activity; KrasG12D/MAPK-mediated TGIF1 phosphorylation suppresses this function in human PDACs; ablating Twist1 in KrasG12D;Tgif1KO mice completely blunts PDAC formation, establishing that TGIF1 restrains KrasG12D-driven PDAC through antagonism of Twist1. |
Co-immunoprecipitation, conditional knockout mouse PDAC models, genetic epistasis (Twist1 ablation rescue), mechanistic phosphorylation experiments |
The EMBO journal |
High |
31268604
|
| 2014 |
TGIF1 interferes with MEIS1-dependent transcriptional programs in MLL-rearranged AML by associating with MEIS1-bound chromatin regions in a competitive manner; forced TGIF1 expression promotes differentiation and cell cycle exit in MLL-AF9-transformed cells and delays leukemic onset in vivo. |
ChIP, in vitro differentiation and cell cycle assays, in vivo leukemia transplantation model, gene expression analysis |
Leukemia |
Medium |
25349154
|
| 2012 |
TGIF1 plays a role in TNF-α- and radiation-induced proinflammatory phenotype of endothelial cells; TGIF1 knockdown inhibits both TNF-α- and radiation-induced p38 MAPK pathway activation (but not NF-κB activation), and TGIF1 deficiency reduces radiation-induced proinflammatory cytokine expression in vivo, identifying p38 MAPK as the signaling pathway through which TGIF1 promotes inflammation. |
TGIF1 overexpression and siRNA knockdown in HUVECs, p38 MAPK and NF-κB pathway activation assays, in vivo radiation enteropathy model with Tgif1-/- mice |
The Journal of biological chemistry |
Medium |
22995913
|
| 2021 |
TGIF1 utilizes a C-terminal SIN3A-interacting domain (SID) that adopts an amphipathic helix to bind the hydrophobic cleft of SIN3A PAH2; residues F379, L382, and V383 are critical for binding; the same SID also mediates TGIF1 homodimerization, suggesting a competitive relationship between dimerization and SIN3A-PAH2 binding. |
NMR structure determination of TGIF1-SID bound to SIN3A PAH2, mutagenesis of critical residues, ITC binding assays |
International journal of molecular sciences |
High |
34884456
|
| 2018 |
The helix α3 of TGIF1-HD constitutes the primary DNA-binding interface as determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) and confirmed by CEST NMR spectroscopy; residues R220 and R221 in α3 are crucial for DNA binding, and DNA binding induces conformational changes in α1 and α2 as well. |
HDX-MS, CEST NMR spectroscopy, NMR titration |
Biochimica et biophysica acta. Proteins and proteomics |
High |
30048701
|
| 2025 |
A vertebrate-conserved short motif (I302-L310) of TGIF1 binds to a groove on the SMAD2 MH2 domain surface that overlaps with coactivator binding sites; BiFC assays confirmed that the α2-β8 loop of SMAD2-MH2 is key for TGIF1 binding, suggesting TGIF1 represses TGFβ signaling by competing with coactivators for SMAD2-MH2 binding. |
NMR titration, HDX-MS, AlphaFold3 modeling, bimolecular fluorescence complementation (BiFC) assays |
FEBS letters |
Medium |
40395157
|
| 2024 |
Tgif1 acts as a transcriptional repressor of p21-activated kinase 3 (Pak3) in osteoblasts; absence of Tgif1 leads to increased Pak3 expression, which impairs focal adhesion formation, osteoblast spreading, and migration on collagen type I matrices; Tgif1 is also required for osteoblast recruitment to bone surfaces during regeneration and PTH 1-34 treatment in vivo. |
Conditional KO osteoblasts, cell morphology and adhesion assays, migration assays on collagen I, ChIP/transcriptional repression assays for Pak3, in vivo bone regeneration and PTH treatment models |
eLife |
High |
38661167
|
| 2025 |
Tgif1 is expressed in osteoclast precursors with increasing expression during RANKL/M-CSF-induced differentiation; cell-autonomous deletion of Tgif1 in the osteoclast lineage impairs differentiation and resorption capacity; mechanistically, Tgif1 restricts ERK1/2 dephosphorylation by suppressing protein phosphatase 2A (PP2A), and PP2A inhibition restores differentiation of Tgif1-deficient osteoclasts. |
Conditional KO in osteoclast lineage, in vitro differentiation assays, PP2A inhibition rescue, ERK1/2 phosphorylation analysis, in vivo aging bone loss model |
Journal of bone and mineral research |
High |
40810487
|
| 2022 |
TFEB transcriptionally activates TGIF1 expression by binding the Tgif1 promoter; in epicardial cells, TFEB overexpression prevents TGFβ-induced EMT, and this effect is abolished by Tgif1 silencing, establishing a TFEB→TGIF1 axis that represses TGFβ-driven EMT. |
Reporter assays, qRT-PCR, TGIF1 silencing rescue experiments, in vitro EMT assays, in vivo epicardial TFEB overexpression mouse model |
Nature communications |
Medium |
36057632
|
| 2016 |
TGIF1 interacts with the PAH2 domain of SIN3A; SID decoy peptides that disrupt this interaction dissociate TGIF1 from the SIN3A complex, inhibit Wnt target gene expression, reduce nuclear β-catenin, and suppress cancer cell invasion; TGIF1 knockdown phenocopies SID decoy effects on Wnt targets and invasion. |
SID decoy peptide treatment, TGIF1 knockdown, Wnt reporter assays, β-catenin localization by immunofluorescence, Transwell invasion assays |
Oncotarget |
Medium |
29179446
|
| 2015 |
TGIF1 represses Sox9 expression by interacting with TGFβ-activated Smad2, suppressing Smad2 phosphorylation, and thereby inhibiting chondrogenic differentiation of tendon-derived stem cells; TGIF1 silencing upregulates chondrogenic markers and increases fibrocartilage formation at the tendon-bone interface in a rat model. |
siRNA knockdown, TGIF1 overexpression in TDSCs, Co-IP for Smad2 interaction, Western blot for Smad2 phosphorylation, in vivo rat tendon repair model |
Cellular physiology and biochemistry |
Medium |
26599628
|
| 2016 |
Tgif1 deficiency in extra-embryonic tissue (but not epiblast) is the critical cause of gastrulation failure in Tgif1/Tgif2 double-null embryos; a single wild-type allele of Tgif1 in extra-embryonic tissue rescues gastrulation, demonstrating that extra-embryonic Tgif function is required for patterning the epiblast. |
Epiblast-specific conditional deletion of Tgif1 using Cre-lox genetics |
PloS one (Tgif1 and Tgif2 Regulate Axial Patterning in Mouse) |
Medium |
20040491 27187787
|
| 2025 |
TGIF1 is enriched on the miR-106b-5p promoter and promotes miR-106b-5p expression; miR-106b-5p in turn suppresses EGR2; in a T2D mouse model, TGIF1 overexpression reduces hyperglycemia and lipid accumulation through the miR-106b-5p/EGR2 axis, and miR-106b-5p inhibition or EGR2 overexpression partially reverses the TGIF1 effect. |
ChIP for TGIF1 at miR-106b-5p promoter, dual-luciferase reporter assays, TGIF1 overexpression in T2D mice, rescue experiments |
BMJ open diabetes research & care |
Medium |
39842865
|