| 1991 |
TEF-1 (TEAD1) was cloned and shown to specifically bind the SV40 GT-IIC and Sph enhansons. Its trans-activation function is mediated by a highly limiting, cell-specific, titratable transcriptional intermediary factor(s), demonstrated by squelching/repression assays and GAL4 chimera experiments in HeLa and MPC11 cells. Translation initiates exclusively at an AUU codon in vivo. |
cDNA cloning, in vitro/in vivo transcription assays, GAL4 chimera squelching experiments, cell-free transcription |
Cell |
High |
1851669
|
| 1994 |
Muscle-enriched TEF-1 (TEAD1) isoforms TEF-1A and TEF-1B bind M-CAT elements from muscle-specific promoters with high affinity and in a sequence-specific manner. The C-terminal exon unique to TEF-1B confers transcriptional activation ability, whereas the equivalent domain of TEF-1A cannot activate transcription when linked to a heterologous DNA-binding domain. |
cDNA cloning from chick heart, electrophoretic mobility shift assay (EMSA), transient transfection with GAL4 chimera reporter assays |
The Journal of biological chemistry |
High |
8106348
|
| 2002 |
TEF-1 (TEAD1) physically interacts with the MADS domain of MEF2 transcription factors, requiring additional sequences in both proteins' activation domains beyond the MADS domain alone for in vivo association. This interaction functionally co-activates muscle-specific promoters. |
Co-immunoprecipitation, GST pull-down assay, mammalian two-hybrid assay, transient transfection reporter assays |
Biochemical and biophysical research communications |
Medium |
12061776
|
| 2004 |
A missense mutation Y421H in TEAD1 is the causative allele in Sveinsson's chorioretinal atrophy (SCRA). Y421 lies in a conserved C-terminal region that is a potential binding site for the co-factor YAP65, which is expressed in human retina along with TEAD1. |
Genome-wide linkage analysis, sequencing, LOD score analysis, RT-PCR expression analysis |
Human molecular genetics |
Medium |
15016762
|
| 2005 |
TEAD1 (TEF-1) interacts with the transcriptional co-activator TAZ both in vitro and in vivo. TAZ interacts with TEAD1 while TEAD1 is bound to MCAT DNA. TAZ interacts more efficiently with TEF-1 (TEAD1) than with RTEF-1 (TEAD4), demonstrating differential co-activator association among TEAD family members. |
GST pull-down assay, co-immunoprecipitation, modified mammalian two-hybrid assay, EMSA with purified proteins |
The Biochemical journal |
High |
15628970
|
| 2007 |
The SCRA-associated missense mutation Y410H in mouse Tead1 (corresponding to human Y421H) abolishes direct interaction between Tead1 and co-factors YAP and TAZ, but not with Vgl-1, -2, or -3. The mutation eliminates the transcriptional activity of Tead1 when co-expressed with YAP or TAZ, establishing that Y421 is essential for YAP/TAZ binding. |
Mammalian two-hybrid assay, GST pull-down with purified proteins, site-directed mutagenesis, transcriptional reporter assays in RPE-J cells |
Biochemical and biophysical research communications |
High |
17689488
|
| 2008 |
Tead1 and Tead2 are functionally redundant in mouse development; double-knockout embryos die at E9.5 with severe growth defects including absence of notochord, closed neural tube, and somites. Genetic interaction experiments demonstrate that Tead1/Tead2 use YAP as a major co-activator in vivo. Tead1/Tead2 double-knockout embryos show reduced cell proliferation and increased apoptosis. |
Generation of Tead1 and Tead2 knockout mice, genetic epistasis with Yap mutants, embryo phenotyping, cell proliferation/apoptosis assays |
Molecular and cellular biology |
High |
18332127
|
| 2010 |
Taz and its co-activator Tead1 regulate expression of the EMT transcription factor Zeb1 in RPE cells. Nuclear translocation of Taz-TEAD1 coincides with loss of cell-cell contact and onset of Zeb1 expression. shRNA knockdown of Taz prevents Zeb1 overexpression and blocks proliferation, repression of Mitf, and EMT. Taz directly binds the Zeb1 promoter in vivo. |
shRNA knockdown, real-time PCR, immunofluorescence for subcellular localization, chromatin immunoprecipitation (ChIP) |
Investigative ophthalmology & visual science |
Medium |
20207963
|
| 2011 |
TEAD1 directly regulates FoxO3a transcription in skeletal muscle by binding to the M-CAT element in the foxo3a promoter, as demonstrated by ChIP-on-chip, independent ChIP-PCR, EMSA, and luciferase reporter assays. Overexpression and inhibition experiments confirm FoxO3a is positively regulated by TEAD1. |
ChIP-on-chip, ChIP-PCR, EMSA, luciferase reporter assay, overexpression/knockdown experiments |
BMC molecular biology |
Medium |
21211055
|
| 2012 |
TEAD1 overexpression arrests the C2C12 myoblast cell cycle and promotes differentiation. TEAD1 directly regulates three novel target genes: Mrpl21 and Ndufa6 (upregulated during differentiation) and Ccne1 (downregulated). Regulation was confirmed by promoter activity assays. |
Overexpression experiments, expression analysis, promoter activity measurement assay, cell cycle analysis |
Cellular signalling |
Medium |
23220227
|
| 2016 |
Tead1 and co-activators Yap and Taz are required for PMP22 expression in Schwann cells, as well as for expression of Egr2. Tead1 directly binds PMP22 and Egr2 enhancers early in development and its binding is induced during myelination, correlating with PMP22 expression. |
ChIP, analysis of enhancer histone modifications, KD/KO with gene expression readouts, developmental binding analysis |
Human molecular genetics |
Medium |
27288457
|
| 2016 |
Myofiber-specific TEAD1 overexpression in transgenic mice causes non-cell-autonomous hyperplasia of satellite cells (muscle stem cells) without affecting muscle tissue size, establishing that TEAD1 in myofibers activates a signaling pathway that determines satellite cell pool size. |
Transgenic mouse overexpression model, satellite cell quantification, regeneration assays, muscle injury models |
eLife |
Medium |
27725085
|
| 2016 |
TEAD1 enhances CRC cell proliferation by directly binding the SP1 promoter and activating SP1 expression, as demonstrated by luciferase assay and ChIP assay. |
Luciferase reporter assay, ChIP assay, siRNA knockdown, overexpression, cell proliferation assays |
Biomedicine & pharmacotherapy |
Low |
27434865
|
| 2017 |
Tead1 is a cell-autonomous direct transcriptional activator of SERCA2a and the SR-associated protein phosphatase 1 regulatory subunit Inhibitor-1 (I-1) in adult cardiomyocytes. Tead1 deletion causes lethal dilated cardiomyopathy, decreasing SERCA2a and I-1 protein levels, increasing PP1 activity, accumulating dephosphorylated phospholamban, and impairing excitation-contraction coupling. |
Tamoxifen-inducible CM-specific Tead1 knockout, global transcriptomic analysis, mechanistic biochemical assays (PP1 activity, phospholamban phosphorylation), iPSC-derived CM validation |
JCI insight |
High |
28878117
|
| 2018 |
TEAD1 occupies chromatin at AQP4, EGFR, and CDH4 loci in glioblastoma stem cells, validated by ChIP-PCR. CRISPR-Cas9 knockout of TEAD1 robustly diminishes GBM cell migration in vitro and in vivo, with consistent downregulation of its target AQP4. TEAD1 overexpression restores AQP4 expression and rescues migratory deficits in TEAD1-KO cells. |
ATAC-seq, ChIP-PCR, CRISPR-Cas9 KO, in vitro and in vivo migration assays, transcriptome analysis, overexpression rescue |
Nature communications |
High |
30275445
|
| 2018 |
YAP1-TEAD1 signaling controls mitochondrial biogenesis and angiogenesis in endothelial cells through PGC1α. TEAD1 knockdown decreases PGC1α expression and suppresses mitochondrial biogenesis, glycolysis, and oxygen consumption. A YAP1 mutant (S94A) that fails to bind TEAD1 attenuates these effects. |
siRNA knockdown, YAP1 mutant constructs (S127A/S94A), in vitro angiogenesis sprouting assay, in vivo fibrin gel vascular morphogenesis, oxygen consumption measurement |
Microvascular research |
Medium |
29680477
|
| 2019 |
VGLL3 binds TEAD1, TEAD3, and TEAD4 in myoblasts and/or myotubes, as identified by interaction proteomics. VGLL3 mainly represses gene expression, regulating similar genes to those regulated by YAP and TAZ. siRNA-mediated Vgll3 knockdown suppresses myoblast proliferation, and Vgll3 overexpression promotes myogenic differentiation. |
Interaction proteomics (pulldown/MS), siRNA knockdown, overexpression, gene expression analysis |
Journal of cell science |
Medium |
31138678
|
| 2019 |
TEAD1 is essential for vascular smooth muscle cell (VSMC) differentiation and cardiovascular development. CMC/VSMC-specific Tead1 deletion causes embryonic lethality by E14.5 due to hypoplastic cardiac and vascular walls and impaired proliferation. TEAD1 transcriptionally activates Pitx2c as a novel target gene, and Pitx2c and myocardin rescue TEAD1-dependent defects in VSMC differentiation. Pitx2c directly interacts with myocardin to augment VSMC differentiation. |
Conditional Tead1 KO mice, whole transcriptome analysis, in vitro rescue experiments, identification of Pitx2c as transcriptional target, co-IP for Pitx2c-myocardin interaction |
Cell death and differentiation |
High |
31024075
|
| 2019 |
TEAD1 directly activates the miR-222 promoter by physically binding to it (validated by ChIP assay) in gastric cancer cells. TEAD1 knockdown decreases miR-222 expression and increases VGLL4 expression, establishing a miR-222/VGLL4/YAP-TEAD1 regulatory loop. |
ChIP assay, siRNA knockdown, luciferase assay, expression analysis |
American journal of cancer research |
Low |
26045994
|
| 2019 |
Tead1 is required for perinatal cardiomyocyte proliferation. Perinatal CM-specific deletion of Tead1 (Myh6-Cre) leads to lethal dilated cardiomyopathy by postnatal day 9 due to significantly decreased CM proliferation. Cell-autonomous Tead1 function is required for normal CM proliferation, associated with decreased levels of cell cycle-promoting proteins. |
Perinatal CM-specific conditional KO (Myh6-Cre), echocardiography, histology, proliferation assays, HL-1 cell line KO confirmation |
PloS one |
Medium |
30811446
|
| 2020 |
YAP-TEAD1 complex targets key genes encoding proteins involved in cytoskeleton dynamics in human pluripotent stem cells, controlling focal adhesion gene transcription and intracellular tension. YAP-TEAD1 inactivation is needed to adjust PSC mechanical properties in response to physiological substrate stiffness during germ layer specification. |
Tankyrase inhibition (AMOT/YAP axis), TEAD1 reporter assays, gene expression analysis, mechanobiology assays |
Cell death and differentiation |
Low |
33116297
|
| 2020 |
Tead1 directly suppresses Apln (apelin) transcription in myogenic cells; Tead1 knockdown stimulates Apln secretion in vitro and myofiber-specific Tead1 overexpression suppresses Apln secretion in vivo. Secreted apelin acts on endothelial Aplnr to stimulate endothelial cell expansion, establishing a Tead1-Apln paracrine axis from myogenic to endothelial cells. |
Yeast one-hybrid screen, single-cell RNA-seq, siRNA knockdown, myofiber-specific overexpression in vivo, co-culture assays, Apln peptide supplementation |
iScience |
Medium |
35789856
|
| 2021 |
Tead1 deletion in adult cardiomyocytes activates necroptosis (not apoptosis) and causes lethal dilated cardiomyopathy. Mechanistically, Tead1 directly activates nuclear DNA-encoded mitochondrial genes required for electron transport chain assembly and ATP production (genome-wide ChIP-seq). Loss of Tead1 increases mitochondrial ROS, disrupts mitochondrial structure, and reduces complex I–IV oxygen consumption. Necrostatin-1 blocks necroptosis and rescues Tead1-deletion-induced heart failure. |
CM-specific and ubiquitous Tead1 KO, RNA-seq, ChIP-seq, mitochondrial function assays, necrostatin-1 rescue, inflammatory marker quantification |
Cell death and differentiation |
High |
33469230
|
| 2021 |
VGLL1 co-activates TEAD1-mediated transcription of HPV early genes. TEAD1 binds 11 sites in the HPV16 long control region (LCR) identified by in vitro DNA pulldown; 8 contribute to early promoter activation. VGLL1 is recruited to the HPV16 LCR via its interaction with TEAD1 both in vitro and in vivo. Knockdown of VGLL1 and/or TEAD1 decreases viral early gene expression. |
In vitro DNA pulldown, luciferase reporter assays, ChIP, siRNA knockdown, co-IP |
Journal of virology |
Medium |
32132238
|
| 2021 |
YAP/TEAD1 complex directly represses cardiac TLR genes. TEAD1 directly binds genomic regions adjacent to Tlr1–7 and Tlr9 in cardiomyocytes. YAP/TEAD1 repression of Tlr4 depends on a conserved TEAD1 binding motif near its transcription start site (luciferase reporter). Cardiomyocyte-specific YAP depletion increases TLR gene expression, pro-inflammatory cytokines, and cardiac susceptibility to LPS. |
ChIP-seq/ChIP, luciferase reporter assay, CM-specific YAP KO, gene expression analysis, LPS challenge |
International journal of molecular sciences |
Medium |
34206257
|
| 2021 |
Tead1 overexpression (replacing TBX5 in a GMT cocktail) nearly 3-fold increases cardiac troponin T expression in fibroblasts compared to GMT alone, increases H3K4me3 at cardio-differentiation and mitochondrial biogenesis gene promoters, and enables cell contractility (beating). YAP and TAZ failed to enhance cTnT expression. |
Fibroblast reprogramming assay, immunofluorescence for cTnT/sarcomere, ChIP for H3K4me3, beating cell assay |
Journal of the American Heart Association |
Medium |
34889103
|
| 2022 |
TEAD1 has a pocket region-independent direct transcriptional repression mechanism controlling cell proliferation. TEAD1 directly represses a class of target genes by interfering with RNA polymerase II (POLII) binding to target promoters, independently of YAP/TAZ/VGLL4 co-factor binding to the TEAD1 hydrophobic pocket. TEAD1 overexpression represses tumor cell proliferation; β cell-specific TEAD1 KO increases cell-autonomous β cell proliferation. TEAD1 controls transcription in a motif-dependent, orientation-independent manner. |
Conditional KO, transcriptomic profiling, cistromic analysis (ChIP-seq), overexpression in cancer cell lines, POLII ChIP, promoter orientation assays |
Nucleic acids research |
High |
36484096
|
| 2022 |
RBFOX2 promotes inclusion of TEAD1 exon 6 via binding to a conserved GCAUG element in the downstream intron, generating full-length TEAD1. The full-length isoform has greater transcriptional activity and oncogenic properties than the TEAD1ΔE6 isoform, with the difference attributable to differential YAP interaction. |
Alternative splicing analysis, public database correlation, isoform-specific functional assays, RBFOX2 KD, RNA-binding motif analysis |
Nucleic acids research |
Medium |
35699208
|
| 2022 |
VGLL4 and MENIN function as TEAD1 co-repressors in pancreatic β cells. Both proteins bind TEAD1 and repress expression of its target genes FZD7 and CCN2, leading to inhibition of β cell proliferation. β cell-specific TEAD1 deletion results in cell-autonomous increase in β cell proliferation, while deletion of canonical co-activators YAP and TAZ does not affect proliferation. |
Improved split-GFP system, yeast two-hybrid, conditional KO (TEAD1, YAP, TAZ in β cells), gene expression analysis |
Cell reports |
Medium |
36662616
|
| 2023 |
Mutant Lamin A/C (Q353R) traps TEAD1 at the nuclear membrane in cardiomyocytes, preventing it from activating cardiac developmental gene targets, causing dilated cardiomyopathy. Inhibition of the Hippo pathway rescued dysregulation of cardiac developmental genes caused by TEAD1 trapping in LMNA-mutant cardiomyocytes. |
Single-cell RNA-seq, ATAC-seq, protein array, electron microscopy, Hippo pathway inhibitor rescue experiments, human DCM patient tissue validation |
Science advances |
High |
37058558
|
| 2024 |
TEAD1 is SUMOylated at lysine 173 by SUMO1, a modification regulated by SENP1-mediated deSUMOylation during cardiac hypertrophy. SUMOylation affects TEAD1 protein stability, nuclear localization, DNA-binding ability, and enhances its interaction with YAP1. DeSUMOylation of TEAD1 (K173R mutant) markedly exacerbates cardiomyocyte enlargement in vitro and in hypertrophy mouse models. |
SUMOylation assays, site-directed mutagenesis (K173R), co-IP, nuclear localization imaging, AAV9-mediated in vivo cardiac expression, mouse hypertrophy model |
Advanced science |
High |
38225750
|
| 2024 |
TM7SF3 controls alternative splicing of TEAD1 by maintaining the splicing factor hnRNPU. TM7SF3 deletion inhibits hnRNPU, causing exclusion of inhibitory exon 5 and generating a more transcriptionally active TEAD1 isoform that promotes hepatic stellate cell (HSC) activation and liver fibrosis. An antisense oligomer (ASO) that blocks TEAD1 alternative splicing deactivates HSCs in vitro and reduces MASH-induced liver fibrosis in vivo. |
Genetic deletion (TM7SF3 KO), liver organoids, primary human HSCs, in vivo MASH mouse model, splicing analysis, ASO intervention |
Cell metabolism |
High |
38670107
|
| 2024 |
TEAD1 promotes cardiac fibroblast-to-myofibroblast transition through the BRD4/Wnt4 signaling pathway. Wnt4 is a novel direct TEAD1 transcriptional target identified by RNA-seq and ChIP-seq. TEAD1 interacts with BET protein BRD4 (demonstrated by Co-IP/mass spectrometry and ChIP), leading to binding and activation of the Wnt4 promoter. CFs-specific TEAD1 KO and TEAD1 inhibitor VT103 ameliorate TAC-induced cardiac remodeling. |
Conditional CF/myofibroblast-specific TEAD1 KO, RNA-seq, ChIP-seq, Co-IP with mass spectrometry, luciferase assay, TAC and Ang-II mouse models, pharmacological inhibition with VT103 |
Signal transduction and targeted therapy |
High |
38374140
|
| 2024 |
TEAD1 is essential for Schwann cell developmental myelination and nerve regeneration. TEAD1 promotes myelination by positively and negatively regulating SC proliferation, enabling Krox20/Egr2 to upregulate myelin proteins, and upregulating cholesterol biosynthetic enzymes FDPS and IDI1. Non-myelinating SCs uniquely require TEAD1 to enwrap nociceptive axons in Remak bundles. |
Conditional and inducible TEAD1 KO mice, SC-specific phenotyping, gene expression analysis, electron microscopy |
eLife |
High |
38456457
|
| 2024 |
Endothelial YAP/TEAD1 complex promotes CXCL17 transcription in hepatic endothelial cells during ischemia-reperfusion. Hypoxia-reoxygenation activates the YAP/TEAD1 complex to upregulate CXCL17, which recruits myeloid-derived suppressor cells (MDSCs) via GPR35 to attenuate liver injury. |
Bulk RNA-seq, in vivo YAP/TEAD1 manipulation, CXCL17 reporter, adoptive transfer experiments, mouse IRI model |
Hepatology |
Low |
38407233
|