Affinage

GTF2I

General transcription factor II-I · UniProt P78347

Length
998 aa
Mass
112.4 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GTF2I encodes TFII-I, a multifunctional transcription factor that integrates growth factor, stress, and cell cycle signals to regulate gene expression through initiator (Inr) and E-box elements, while also performing a cytoplasmic role in suppressing calcium entry (PMID:8377828, PMID:17023658). In the nucleus, TFII-I activates target genes including c-fos, cyclin D1, and Grp78 following c-Src- or ERK-dependent tyrosine phosphorylation at Y248/Y611, which drives its nuclear translocation; its transcriptional output is further tuned by SUMO1 modification (written by PIAS4, erased by SENP2) that relieves HDAC3-mediated repression, by Cdk1 phosphorylation at G2/M that displaces it from condensing chromatin, and by p53/ATM-dependent ubiquitin-proteasomal degradation during genotoxic stress (PMID:11934902, PMID:25869096, PMID:19182516, PMID:16314517). In the cytoplasm, TFII-I competes with TRPC3 channels for PLC-γ binding to suppress agonist-induced calcium entry (PMID:17023658). In neurons, GTF2I controls myelination gene expression and oligodendrocyte maturation through an LSD1-dependent axis, and the recurrent somatic L424H mutation drives thymic epithelial cell transformation and thymoma formation in vivo (PMID:31011227, PMID:38019906, PMID:32034314, PMID:36049655).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1993 High

    Identification of TFII-I as an Inr-binding transcription initiation factor established a TFIIA-independent pathway for activating TATA-less promoters and revealed that Myc can antagonize this function by disrupting TBP–TFII-I–promoter complexes.

    Evidence In vitro transcription reconstitution with defined factors and protein–protein interaction analysis

    PMID:8377828 PMID:8377829

    Open questions at the time
    • Crystal structure of TFII-I on Inr DNA not determined
    • Relative contribution of TFII-I vs. other Inr factors in vivo unknown
    • Mechanism by which Myc displaces TBP–TFII-I complex not resolved at atomic level
  2. 1998 High

    Demonstration that tyrosine phosphorylation is required for TFII-I transcriptional activation—but not DNA binding—separated its DNA-recognition and transactivation functions and implicated upstream kinase signaling.

    Evidence In vivo phosphorylation assay with site-directed mutagenesis and reporter gene assays

    PMID:9837922

    Open questions at the time
    • Identity of the responsible kinase not yet established at this stage
    • Specific phosphorylation sites not mapped
  3. 2002 High

    Mapping c-Src-dependent phosphorylation to Y248 and Y611 and linking it to reversible nuclear translocation and c-fos activation defined the signal-responsive shuttling mechanism of TFII-I, while simultaneous discovery of HDAC3 as a direct repressive partner explained how TFII-I transcriptional output is restrained.

    Evidence Mutagenesis, subcellular fractionation, reporter assays, co-IP/GST pull-down/co-localization, and HDAC enzymatic assays

    PMID:11934902 PMID:12393887

    Open questions at the time
    • How HDAC3 is released upon activation signals not resolved
    • Whether other HDACs participate is untested
    • Structural basis of c-Src recognition of Y248/Y611 unknown
  4. 2005 High

    Extension of TFII-I function to ER stress (Grp78 induction via c-Src/Y248) and cell cycle control (cyclin D1 activation, p53/ATM-dependent proteasomal degradation) broadened the model from a signal-responsive activator to a node linking stress and proliferation.

    Evidence ChIP, stable knockdown, ubiquitination and proteasome inhibition assays, flow cytometry, and SELEX/EMSA for I-repeat domain DNA binding

    PMID:15664986 PMID:15987678 PMID:16314517

    Open questions at the time
    • E3 ubiquitin ligase mediating p53-dependent TFII-I degradation not identified
    • Relative importance of individual I-repeat domains for in vivo target selection unclear
  5. 2006 High

    Discovery that cytoplasmic TFII-I suppresses TRPC3-mediated calcium entry by competing with TRPC3 for PLC-γ binding established a major non-transcriptional function and connected GTF2I haploinsufficiency to the hypersociability phenotype of Williams–Beuren syndrome.

    Evidence Calcium entry assays, co-IP, domain mapping of PH-like and phosphotyrosine interactions with PLC-γ

    PMID:17023658

    Open questions at the time
    • In vivo confirmation of calcium entry dysregulation in GTF2I-haploinsufficient neurons not shown
    • Whether other TRP channels are similarly regulated is untested
  6. 2006 Medium

    Interaction with Bright/ARID3a at immunoglobulin loci and control of B-cell growth arrest via NF-κB (c-rel nuclear translocation, p50 DNA binding) positioned TFII-I as a regulator of B-cell receptor signaling and differentiation.

    Evidence Co-IP with domain mapping, siRNA knockdown, reporter assays, EMSA, flow cytometry in WEHI-231 B cells

    PMID:16738337 PMID:17312101

    Open questions at the time
    • Genome-wide B-cell targets of TFII-I not mapped
    • Whether TFII-I directly binds NF-κB subunits or acts indirectly unresolved
  7. 2009 Medium

    Identification of Cdk1 as a G2/M-phase kinase for TFII-I, causing chromatin displacement during prophase, and of craniofacial target genes (Cfdp1, Sec23a, Nsd1) expanded the cell cycle and developmental scope of TFII-I function.

    Evidence In vitro kinase assay, flow cytometry, ChIP with siRNA validation, microarray

    PMID:18579769 PMID:19182516

    Open questions at the time
    • Cdk1 phosphorylation site(s) on TFII-I not mapped
    • Functional consequences of craniofacial target gene regulation in vivo not tested
  8. 2011 Medium

    Physical interaction with BRCA1 at irradiation-induced foci and co-activation of the SIRT1 promoter linked TFII-I to the DNA damage response transcriptional program, while Src-dependent repression of SSeCKS/AKAP12 added a repressive role at specific loci.

    Evidence Co-IP with domain mapping, immunofluorescence of nuclear foci, reporter assays, MS-based promoter complex identification, ChIP

    PMID:20568114 PMID:21407215

    Open questions at the time
    • Whether TFII-I is required for homologous recombination not tested
    • Whether SSeCKS repression is relevant to Src-driven transformation in vivo unknown
  9. 2014 Medium

    Genome-wide ChIP-seq revealed context-dependent binding of TFII-I upstream and downstream of TSS at active versus repressed genes, and physical interaction with Elongin A implicated TFII-I in transcription elongation control; ERK-dependent phosphorylation was confirmed as another nuclear translocation trigger.

    Evidence ChIP-seq with biotinylation tagging, pull-down with Elongin A, siRNA, ChIP and confocal microscopy with ERK inhibitor

    PMID:24875474 PMID:24933421

    Open questions at the time
    • Elongin A interaction awaits reciprocal validation and structural characterization
    • Distinction between Src- and ERK-phosphorylated TFII-I target gene programs not resolved
  10. 2015 High

    Site-specific mapping of SUMO1 modification at K221/K240, identification of PIAS4 as writer and SENP2 as eraser, and demonstration that SUMOylation reduces HDAC3 binding provided a mechanistic toggle that switches TFII-I between repressed and active states.

    Evidence Mass spectrometry, mutagenesis at SUMO sites, IP-Western, transcriptional and proliferation assays

    PMID:25869096

    Open questions at the time
    • Structural basis of SUMO-mediated HDAC3 displacement unknown
    • Signal(s) that trigger SUMOylation in physiological contexts not identified
  11. 2016 High

    Adenovirus E4-ORF3 exploits the SUMO–ubiquitin axis to degrade TFII-I and derepress a viral promoter, establishing TFII-I as a host restriction factor targeted during infection.

    Evidence Infection assay, SUMOylation/ubiquitination assays, proteasome inhibition, reporter assay with species C specificity control

    PMID:26814176

    Open questions at the time
    • Which E3 ubiquitin ligase is recruited by E4-ORF3 for TFII-I degradation not identified
    • Breadth of TFII-I antiviral restriction beyond Ad species C untested
  12. 2019 High

    Conditional neuronal knockout of Gtf2i demonstrated that TFII-I in excitatory neurons non-cell-autonomously controls oligodendrocyte maturation and myelination gene expression; drug-induced myelination rescue reversed behavioral deficits, establishing a causal GTF2I–myelination–behavior axis.

    Evidence Cre-lox conditional KO, transcriptome analysis, electron microscopy, electrophysiology, clemastine rescue, human post-mortem cortex validation

    PMID:31011227

    Open questions at the time
    • Neuron-to-oligodendrocyte signaling mediator downstream of TFII-I not identified
    • Whether myelination defects contribute to Williams–Beuren syndrome cognitive phenotype in humans not directly shown
  13. 2020 High

    The thymoma-associated GTF2I L424H mutation was shown to be sufficient for thymic epithelial cell transformation, acting through COX-2 upregulation and altered glycolytic gene expression, and conditional knock-in in mice produced thymomas with impaired medullary development.

    Evidence Knockin cell line and conditional knock-in mouse model with transformation assays, transcriptomics, metabolomics, COX-2 inhibition, and spatial profiling

    PMID:32034314 PMID:36049655

    Open questions at the time
    • How L424H alters TFII-I DNA binding or protein interactions at the structural level unknown
    • Whether L424H affects SUMO/ubiquitin modification not tested
  14. 2023 High

    GTF2I dosage was shown to control cortical progenitor proliferation and excitatory neuron timing through an LSD1-dependent chromatin axis; LSD1 inhibition rescued ASD-like behaviors in Gtf2i-duplication mice, defining a druggable GTF2I–LSD1 pathway.

    Evidence Patient-derived cortical organoids, single-cell transcriptomics, proteomics, transgenic mice, LSD1 inhibitor rescue, behavioral assays

    PMID:38019906

    Open questions at the time
    • Whether TFII-I directly recruits LSD1 or acts indirectly through an intermediate complex unknown
    • LSD1 genomic targets downstream of GTF2I duplication not comprehensively mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of TFII-I multidomain architecture on DNA, the E3 ligase mediating p53-dependent degradation, the neuron-derived signal that controls oligodendrocyte maturation, and whether the calcium entry and transcriptional functions of TFII-I are coordinately regulated in the same cell.
  • No high-resolution structure of full-length TFII-I or any I-repeat–DNA complex
  • Integration of nuclear and cytoplasmic TFII-I functions in single-cell models not demonstrated
  • Comprehensive phosphoproteomics distinguishing Src- vs. ERK- vs. Cdk1-phosphorylated pools lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 5 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 2 R-HSA-1643685 Disease 2
Partners
ARID3ABRCA1HDAC3LSD1MYCPIAS4PLCG1SENP2

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 TFII-I (GTF2I) was identified as a transcription initiation factor that activates core promoters through an initiator element (Inr), establishing an alternative initiation pathway distinct from TFIIA-dependent initiation. TFII-I and TBP bind cooperatively to Inr-containing TATA-less promoters. In vitro transcription reconstitution assay; preinitiation complex formation analysis Nature High 8377828
1993 Myc physically interacts with TFII-I and cooperatively binds Inr and E-box elements; however, Myc-TFII-I interaction at the Inr inhibits transcription initiation by preventing complex formation between TBP (TFIID), TFII-I, and the promoter. In vitro transcription assay; protein-protein interaction; complex formation analysis Nature High 8377829
1998 TFII-I is phosphorylated in vivo at serine/threonine and tyrosine residues; tyrosine phosphorylation is critical for its transcriptional activation activity (via the Vbeta promoter), but not required for specific DNA binding. Mutation of a consensus tyrosine phosphorylation site severely reduces transcriptional activation in vivo. In vivo phosphorylation assay; site-directed mutagenesis; in vitro transcription; reporter gene assay The Journal of biological chemistry High 9837922
2002 TFII-I undergoes c-Src-dependent tyrosine phosphorylation at tyrosine residues 248 and 611 and reversibly translocates to the nucleus in response to growth factor signaling; nuclear tyrosine-phosphorylated TFII-I activates the c-fos reporter gene. Phosphorylation-deficient mutants fail to activate c-fos. Tyrosine phosphorylation assay; subcellular fractionation/nuclear translocation; reporter gene assay; site-directed mutagenesis; antibody microinjection The Journal of biological chemistry High 11934902
2002 HDAC3 physically interacts with TFII-I (confirmed by co-immunoprecipitation, GST pull-down, and co-localization). The HDAC3 C-terminus (residues 373-401) and TFII-I residues 363-606 are required for the interaction. An anti-TFII-I immunoprecipitate contains histone deacetylase activity, and HDAC3 overexpression severely reduces TFII-I transcriptional activation. Co-immunoprecipitation; GST pull-down; immunofluorescence co-localization; HDAC enzyme assay; mutational analysis; transcriptional activation assay The Journal of biological chemistry High 12393887
2002 Miz1/PIASxbeta/Siz2 (a SUMO E3 ligase) interacts with TFII-I and augments its transcriptional activity; it also interacts with hMusTRD1/BEN. Co-expression of a nuclear-localization-deficient mutant of Miz1 fails to alter TFII-I subcellular localization, and Miz1 relieves repression exerted by nuclear hMusTRD1/BEN on TFII-I. Yeast two-hybrid; co-immunoprecipitation; transcriptional activity assay; subcellular localization analysis The Journal of biological chemistry Medium 12193603
2005 TFII-I is activated by ER stress via c-Src-dependent tyrosine phosphorylation at Tyr248, leading to nuclear translocation and binding to the Grp78/BiP promoter ER stress element. TFII-I is required for optimal ER stress induction of Grp78; c-Src is activated by ER stress (thapsigargin) and stimulates Grp78 promoter activity via TFII-I. Chromatin immunoprecipitation (ChIP); nuclear translocation (fractionation); stable knockdown cell lines; tyrosine phosphorylation assay; reporter gene assay The Journal of biological chemistry High 15664986
2005 TFII-I directly activates the cyclin D1 promoter under normal growth conditions and is recruited to it by ChIP. Upon genotoxic stress and p53 activation, TFII-I is ubiquitinated and degraded by the proteasome in a p53- and ATM-dependent manner. Stable expression of TFII-I accelerates S-phase entry and exit, and overcomes p53-mediated cell cycle arrest. Tyrosine phosphorylation at Y248 and Y611 is required for these cell cycle functions. ChIP; ubiquitination assay; proteasome inhibition; flow cytometry; stable overexpression/knockdown; site-directed mutagenesis Molecular and cellular biology High 16314517
2006 TFII-I acts outside the nucleus as a negative regulator of agonist-induced calcium entry (ACE) by suppressing surface accumulation of TRPC3 channels. TFII-I inhibits ACE via phosphotyrosine residues engaging the SH2 domains of PLC-γ and via an interrupted PH-like domain binding the split PH domain of PLC-γ, competing with TRPC3 for PLC-γ binding. Calcium entry assay; co-immunoprecipitation; domain mapping; cytoplasmic localization experiments; surface TRPC3 accumulation assay Science High 17023658
2006 TFII-I directly interacts with the ARID-family transcription factor Bright/ARID3a through Bright's protein interaction domain; specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. TFII-I inhibition in B cells decreases heavy-chain transcript levels. Co-immunoprecipitation; reporter gene assay; siRNA knockdown; domain mapping Molecular and cellular biology Medium 16738337
2007 Loss of TFII-I function in WEHI-231 B cells (stable knockdown) prevents growth arrest upon anti-IgM or TGF-β signaling, associated with upregulation of c-Myc and downregulation of p21/p27. TFII-I controls NF-κB by regulating nuclear translocation of c-rel and DNA-binding activity of p50 homodimer. Stable siRNA knockdown; flow cytometry; Western blot; EMSA; immunofluorescence Journal of immunology Medium 17312101
2009 TFII-I silencing causes significant delay in S-phase entry and progression and G2/M entry, without major mitotic defects. Cyclin D1 and PKC-β are identified as major downstream transcriptional targets. Cdk1 phosphorylates TFII-I at the G2/M boundary, leading to its displacement from condensed chromatin during prophase to pro-metaphase transition. siRNA knockdown; flow cytometry; microarray; ChIP; Cdk1 kinase assay; functional validation Cell cycle Medium 19182516
2009 TFII-I binds the Grp78 promoter and upregulates GRP78 transcription in prostate cancer cells stimulated with α2-macroglobulin (α2M*). α2M* induces tyrosine phosphorylation of c-Src and TFII-I, and TFII-I relocalizes to the nucleus. TFII-I also binds the c-fos promoter in these cells. ChIP; confocal microscopy (nuclear translocation); radiolabeled amino acid incorporation; siRNA knockdown; tyrosine phosphorylation assay Journal of cellular biochemistry Medium 19097122
2005 GTF2I-like repeats 4 and 6 of TFII-I exhibit DNA binding properties in vitro, supporting the idea that GTF2I-like (I-repeat) domains serve as a common DNA-binding module. SELEX; EMSA; domain mutagenesis The Journal of biological chemistry Medium 15987678
2011 TFII-I physically interacts with BRCA1 (C-terminus of TFII-I with the BRCT domain of BRCA1) in the nucleus; TFII-I enhances BRCA1-mediated transcriptional activation of the SIRT1 promoter and stimulates BRCA1 transactivation function. Both proteins co-localize in irradiation-induced nuclear foci. Co-immunoprecipitation; reporter gene assay; immunofluorescence (nuclear foci); domain mapping British journal of cancer Medium 21407215
2015 TFII-I is SUMOylated at K221 and K240 by SUMO1; PIAS4 is the E3 ligase responsible for TFII-I SUMOylation, and SENP2 is the SUMO protease (deSUMOylase) for TFII-I. SUMOylation reduces TFII-I binding to its repressor HDAC3, thus promoting TFII-I transcriptional activity and cell proliferation/colony formation. Large-scale proteomics/mass spectrometry; immunoprecipitation-Western blot; mutagenesis at SUMO sites; functional transcriptional assays; proliferation assays Journal of proteome research High 25869096
2016 Adenovirus E4-ORF3 stimulates SUMOylation and subsequent ubiquitination of TFII-I, leading to its proteasomal degradation. E4-ORF3 is required for ubiquitination of TFII-I and stimulates activity of a TFII-I-repressed viral promoter during infection. This mechanism is specific to Ad species C E4-ORF3. Infection assay; SUMOylation assay; ubiquitination assay; proteasome inhibition; reporter gene assay; ectopic expression; immunofluorescence mBio High 26814176
2014 17β-estradiol promotes TFII-I phosphorylation via Ras-ERK1/2 signaling, leading to TFII-I nuclear localization and enhanced binding to the Grp78 promoter, resulting in Grp78 induction and protection against ER stress-induced apoptosis in osteoblasts. ERK1/2 inhibition blocks TFII-I phosphorylation. ChIP; confocal microscopy (nuclear localization); reporter gene assay; ERK1/2 inhibitor; Western blot (phospho-TFII-I) Laboratory investigation Medium 24933421
2011 Src-induced tyrosine phosphorylation of TFII-I increases its binding to the SSeCKS/AKAP12 proximal promoter, acting as a transcriptional repressor at this locus. siRNA knockdown of TFII-I or expression of TFII-I Y248/249F mutant derepress SSeCKS in Src-transformed cells. Mass spectrometry (promoter complex identification); ChIP; siRNA knockdown; site-directed mutagenesis; reporter gene assay International journal of cancer Medium 20568114
2014 TFII-I interacts with MAPK pathway via chromatin: TFII-I binds upstream and downstream of TSS at different classes of genes (active vs. repressed). TFII-I interacts with Elongin A (pull-down assay), implicating TFII-I in transcription elongation; partial depletion of TFII-I reduces Elongin A association with DNMT1 and EFR3A without decreasing Pol II recruitment. ChIP-seq (biotinylation tagging); pull-down assay; siRNA knockdown; high-throughput sequencing Nucleic acids research Medium 24875474
2009 TFII-I transcription factors bind to promoters of craniofacial development genes Cfdp1, Sec23a, and Nsd1 in vivo, as demonstrated by ChIP analysis, and siRNA knockdown validates these as direct TFII-I targets. ChIP; siRNA knockdown; bioinformatics (consensus site identification); microarray Proceedings of the National Academy of Sciences of the United States of America Medium 18579769
2017 A GTF2I-BRAF fusion gene (GTF2I exons 1-19 fused to BRAF exon 10 onward) was identified in pilocytic astrocytoma. The GTF2I-BRAF fusion retains an intact BRAF kinase domain while losing the inhibitory N-terminal domain, leading to elevated MAPK pathway activation compared to BRAF-WT in functional assays. RNA sequencing; copy number variation analysis; functional MAPK pathway activation assay PloS one Medium 28448514
2020 The GTF2I L424H mutant (thymoma-associated) induces cell transformation, aneuploidy, increased survival under metabolic stress, altered glycolytic enzyme expression, and elevated cyclooxygenase-2 expression in thymic epithelial cells. Cyclooxygenase-2 was required for the survival and transformation effects of the mutation. Gtf2i L424H knockin cell line; cell transformation assay; transcriptome analysis; metabolomics; COX-2 inhibition Cell death and differentiation High 32034314
2019 Neuronal deletion of Gtf2i in forebrain excitatory neurons causes decreased mRNA levels of myelination genes, reduced mature oligodendrocyte numbers, reduced myelin thickness, and impaired axonal conductivity. Restoring myelination with clemastine or increasing axonal conductivity rescued behavioral deficits (increased sociability, fine motor deficits, anxiety). Conditional neuronal Cre-lox knockout; transcriptome analysis; electron microscopy (myelin thickness); electrophysiology (axonal conductivity); drug rescue (clemastine); post-mortem human cortex analysis Nature neuroscience High 31011227
2021 Gtf2i-β/δ isoforms bind the cis-element 5'-ATTAATAACC-3' in the ARMS2 gene locus (identified by EMSA) and their binding enhances transcription of HTRA1 in transfected cells and AMD patient-derived iPSCs. EMSA; transfection/reporter assay; iPSC-based functional assay The Journal of biological chemistry Medium 33636181
2023 GTF2I dosage controls neural progenitor proliferation and neuronal differentiation in cortical organoids; GTF2I duplication causes precocious excitatory neuron production (rescued by restoring GTF2I levels). GTF2I acts via LSD1 (lysine demethylase 1) as a downstream effector; LSD1 inhibition rescues ASD-like behaviors in Gtf2i-duplication transgenic mice. Patient-derived cortical organoids; single-cell transcriptomics; proteomics; Gtf2i transgenic mice; LSD1 inhibitor treatment; behavioral assays Science advances High 38019906
2021 GTF2I risk allele SNPs (rs73366469, rs117026326) increase GTF2I expression in salivary gland cells and enhance NF-κB p65-dependent NF-κB activation. GTF2I overexpression enhances NF-κB reporter activity dependent on its N-terminal leucine zipper domain. GTF2I knockdown suppresses inflammatory responses in mouse endothelial cells in vitro and in vivo. SNP functional analysis; reporter gene assay; siRNA knockdown; domain analysis (leucine zipper); in vivo knockdown model International immunology Medium 34036345
2022 Conditional knock-in of Gtf2i L424H in Foxn1+ thymic epithelial cells impairs thymic medullary development and maturation of medullary thymic epithelial cells, and causes tumor formation in aged mice. Cell cycle pathways (E2F targets, MYC targets) are enriched in tumor epithelial cells. Conditional knock-in mouse model; digital spatial profiling (GeoMx); immunohistochemistry; transcriptome analysis Journal of thoracic oncology High 36049655

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 A new spin on protein dynamics. Trends in biochemical sciences 338 12069788
2005 Sample preparation and digestion for proteomic analyses using spin filters. Proteomics 331 15761957
1980 Spin-trapping and direct electron spin resonance investigations of the redox metabolism of quinone anticancer drugs. Biochimica et biophysica acta 280 6248123
2009 Nonspecifically bound proteins spin while diffusing along DNA. Nature structural & molecular biology 252 19898474
1993 Direct role for Myc in transcription initiation mediated by interactions with TFII-I. Nature 252 8377829
2014 A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors. Nature genetics 214 24974848
1993 An alternative pathway for transcription initiation involving TFII-I. Nature 153 8377828
2008 Essential functions of the Williams-Beuren syndrome-associated TFII-I genes in embryonic development. Proceedings of the National Academy of Sciences of the United States of America 98 19109438
2009 Partial 7q11.23 deletions further implicate GTF2I and GTF2IRD1 as the main genes responsible for the Williams-Beuren syndrome neurocognitive profile. Journal of medical genetics 97 19897463
2001 Biochemistry and biology of the inducible multifunctional transcription factor TFII-I. Gene 97 11674993
2019 Neuronal deletion of Gtf2i, associated with Williams syndrome, causes behavioral and myelin alterations rescuable by a remyelinating drug. Nature neuroscience 94 31011227
2003 Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on chromosome 7q11.23. Genetics in medicine : official journal of the American College of Medical Genetics 94 12865760
2009 Is it Williams syndrome? GTF2IRD1 implicated in visual-spatial construction and GTF2I in sociability revealed by high resolution arrays. American journal of medical genetics. Part A 88 19205026
1999 Nitroxide spin-spin interactions: applications to protein structure and dynamics. Annual review of biophysics and biomolecular structure 86 10410798
2010 Haploinsufficiency of Gtf2i, a gene deleted in Williams Syndrome, leads to increases in social interactions. Autism research : official journal of the International Society for Autism Research 85 21328569
2016 Helix-Dependent Spin Filtering through the DNA Duplex. Journal of the American Chemical Society 79 27934017
2006 Action of TFII-I outside the nucleus as an inhibitor of agonist-induced calcium entry. Science (New York, N.Y.) 79 17023658
2023 Efficient Spin-to-Charge Conversion via Altermagnetic Spin Splitting Effect in Antiferromagnet RuO_{2}. Physical review letters 68 37295074
2005 Transcriptional regulation of the Grp78 promoter by endoplasmic reticulum stress: role of TFII-I and its tyrosine phosphorylation. The Journal of biological chemistry 65 15664986
2004 EPR spin trapping of protein radicals. Free radical biology & medicine 63 15082061
2012 Duplication of GTF2I results in separation anxiety in mice and humans. American journal of human genetics 59 22578324
2009 Multifrequency electron spin resonance spectra of a spin-labeled protein calculated from molecular dynamics simulations. Journal of the American Chemical Society 56 19191603
2002 Histone deacetylase 3 binds to and regulates the multifunctional transcription factor TFII-I. The Journal of biological chemistry 56 12393887
2017 Feasibility trial for primary stroke prevention in children with sickle cell anemia in Nigeria (SPIN trial). American journal of hematology 55 28439953
2014 Spin selectivity in electron transfer in photosystem I. Angewandte Chemie (International ed. in English) 54 24989350
2017 Time-Dependent Double-Hybrid Density Functionals with Spin-Component and Spin-Opposite Scaling. Journal of chemical theory and computation 53 28763220
2006 Induction of immunoglobulin heavy-chain transcription through the transcription factor Bright requires TFII-I. Molecular and cellular biology 52 16738337
2012 Association of GTF2i in the Williams-Beuren syndrome critical region with autism spectrum disorders. Journal of autism and developmental disorders 51 22048961
2006 Redox thermodynamics of the Fe(III)/Fe(II) couple of human myeloperoxidase in its high-spin and low-spin forms. Biochemistry 51 17042493
1969 Spin-labeled transfer RNA. Proceedings of the National Academy of Sciences of the United States of America 51 4307874
2002 c-Src-dependent transcriptional activation of TFII-I. The Journal of biological chemistry 50 11934902
2011 RNA dynamics: perspectives from spin labels. Wiley interdisciplinary reviews. RNA 48 21882345
2007 Signal-induced functions of the transcription factor TFII-I. Biochimica et biophysica acta 48 17976384
2007 Induction of chromosomally integrated HIV-1 LTR requires RBF-2 (USF/TFII-I) and Ras/MAPK signaling. Virus genes 47 17546494
2017 Pathophysiology of TFII-I: Old Guard Wearing New Hats. Trends in molecular medicine 44 28461154
1998 Regulation of TFII-I activity by phosphorylation. The Journal of biological chemistry 43 9837922
2006 Immuno-spin trapping of DNA radicals. Nature methods 42 16432522
2008 Identification of the TFII-I family target genes in the vertebrate genome. Proceedings of the National Academy of Sciences of the United States of America 40 18579769
2007 Immuno-spin trapping analyses of DNA radicals. Nature protocols 40 17406615
2013 RosettaEPR: rotamer library for spin label structure and dynamics. PloS one 38 24039810
2004 Comparison of TFII-I gene family members deleted in Williams-Beuren syndrome. Protein science : a publication of the Protein Society 38 15388857
2003 Regulation of immunoglobulin promoter activity by TFII-I class transcription factors. The Journal of biological chemistry 36 14645227
2014 Primary stroke prevention in Nigerian children with sickle cell disease (SPIN): challenges of conducting a feasibility trial. Pediatric blood & cancer 35 25399822
1998 A mouse single-copy gene, Gtf2i, the homolog of human GTF2I, that is duplicated in the Williams-Beuren syndrome deletion region. Genomics 35 9521869
2015 Development and Application of Spin Traps, Spin Probes, and Spin Labels. Methods in enzymology 34 26478492
2005 Inhibition of TFII-I-dependent cell cycle regulation by p53. Molecular and cellular biology 34 16314517
1998 SPIN, a substrate in the MAP kinase pathway in mouse oocytes. Molecular reproduction and development 34 9590541
2017 A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma. PloS one 32 28448514
2015 Intracisternal Gtf2i Gene Therapy Ameliorates Deficits in Cognition and Synaptic Plasticity of a Mouse Model of Williams-Beuren Syndrome. Molecular therapy : the journal of the American Society of Gene Therapy 32 26216516
2014 17β-Estradiol inhibits ER stress-induced apoptosis through promotion of TFII-I-dependent Grp78 induction in osteoblasts. Laboratory investigation; a journal of technical methods and pathology 32 24933421
2014 Cognitive-behavioral phenotypes of Williams syndrome are associated with genetic variation in the GTF2I gene, in a healthy population. BMC neuroscience 31 25429715
2009 Transcription factor TFII-I causes transcriptional upregulation of GRP78 synthesis in prostate cancer cells. Journal of cellular biochemistry 31 19097122
1994 ESR studies of spin-labeled membranes aligned by isopotential spin-dry ultracentrifugation: lipid-protein interactions. Biophysical journal 30 7535112
2020 Mutant GTF2I induces cell transformation and metabolic alterations in thymic epithelial cells. Cell death and differentiation 29 32034314
2020 Modeling of spin-spin distance distributions for nitroxide labeled biomacromolecules. Physical chemistry chemical physics : PCCP 29 33107523
2018 Long spin coherence length and bulk-like spin-orbit torque in ferrimagnetic multilayers. Nature materials 29 30510269
2010 Essential role of the N-terminal region of TFII-I in viability and behavior. BMC medical genetics 29 20403157
2023 GTF2I dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders. Science advances 28 38019906
2002 The SUMO ubiquitin-protein isopeptide ligase family member Miz1/PIASxbeta /Siz2 is a transcriptional cofactor for TFII-I. The Journal of biological chemistry 28 12193603
2017 A transcriptional coregulator, SPIN·DOC, attenuates the coactivator activity of Spindlin1. The Journal of biological chemistry 27 29061846
2010 Molecular basis of Williams-Beuren syndrome: TFII-I regulated targets involved in craniofacial development. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 25 20500075
2005 Multiple GTF2I-like repeats of general transcription factor 3 exhibit DNA binding properties. Evidence for a common origin as a sequence-specific DNA interaction module. The Journal of biological chemistry 25 15987678
2015 Variation in the Williams syndrome GTF2I gene and anxiety proneness interactively affect prefrontal cortical response to aversive stimuli. Translational psychiatry 24 26285132
2011 Multifunctional transcription factor TFII-I is an activator of BRCA1 function. British journal of cancer 24 21407215
2020 Primary Driver Mutations in GTF2I Specific to the Development of Thymomas. Cancers 22 32722121
2017 The Williams syndrome prosociality gene GTF2I mediates oxytocin reactivity and social anxiety in a healthy population. Biology letters 22 28424317
2017 Optical spin transfer and spin-orbit torques in thin film ferromagnets. Physical review. B 22 29167836
2015 Functional Proteomics Study Reveals SUMOylation of TFII-I is Involved in Liver Cancer Cell Proliferation. Journal of proteome research 22 25869096
2014 Mitochondria-targeted spin traps: synthesis, superoxide spin trapping, and mitochondrial uptake. Chemical research in toxicology 22 24890552
2011 Water proton spin saturation affects measured protein backbone 15N spin relaxation rates. Journal of magnetic resonance (San Diego, Calif. : 1997) 22 22015249
2019 Gtf2i and Gtf2ird1 mutation do not account for the full phenotypic effect of the Williams syndrome critical region in mouse models. Human molecular genetics 21 31418010
2016 The Adenovirus E4-ORF3 Protein Stimulates SUMOylation of General Transcription Factor TFII-I to Direct Proteasomal Degradation. mBio 21 26814176
2007 Attaching a spin to a protein -- site-directed spin labeling in structural biology. Acta biochimica Polonica 21 17565387
2021 Solid-State NMR of Membrane Proteins in Lipid Bilayers: To Spin or Not To Spin? Accounts of chemical research 20 33655754
2009 Phase specific functions of the transcription factor TFII-I during cell cycle. Cell cycle (Georgetown, Tex.) 20 19182516
2004 The early embryonic expression of TFII-I during mouse preimplantation development. Gene expression patterns : GEP 20 14678824
2020 High-throughput screening identifies histone deacetylase inhibitors that modulate GTF2I expression in 7q11.23 microduplication autism spectrum disorder patient-derived cortical neurons. Molecular autism 19 33208191
2014 Genomic and proteomic analysis of transcription factor TFII-I reveals insight into the response to cellular stress. Nucleic acids research 19 24875474
2003 A spin cell for spin current. Physical review letters 19 12857175
2022 A Knock-In Mouse Model of Thymoma With the GTF2I L424H Mutation. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 18 36049655
2018 The contribution of GTF2I haploinsufficiency to Williams syndrome. Molecular and cellular probes 18 29305905
2009 Williams-Beuren syndrome-associated transcription factor TFII-I regulates osteogenic marker genes. The Journal of biological chemistry 17 19880526
2008 Limits on anomalous spin-spin couplings between neutrons. Physical review letters 17 19113768
2007 Cutting Edge: TFII-I controls B cell proliferation via regulating NF-kappaB. Journal of immunology (Baltimore, Md. : 1950) 17 17312101
2022 Human thymoma-associated mutation of the GTF2I transcription factor impairs thymic epithelial progenitor differentiation in mice. Communications biology 16 36175547
2021 Sjögren's syndrome-associated SNPs increase GTF2I expression in salivary gland cells to enhance inflammation development. International immunology 16 34036345
2021 Dermatan Sulfate Is a Potential Regulator of IgH via Interactions With Pre-BCR, GTF2I, and BiP ER Complex in Pre-B Lymphoblasts. Frontiers in immunology 16 34113352
2019 Spindlin docking protein (SPIN.DOC) interaction with SPIN1 (a histone code reader) regulates Wnt signaling. Biochemical and biophysical research communications 16 30803761
2008 Alternative splicing and promoter use in TFII-I genes. Gene 16 19111598
2021 Binding of Gtf2i-β/δ transcription factors to the ARMS2 gene leads to increased circulating HTRA1 in AMD patients and in vitro. The Journal of biological chemistry 15 33636181
2013 Quantum Mechanical Study of Vicinal J Spin-Spin Coupling Constants for the Protein Backbone. Journal of chemical theory and computation 15 26589175
2003 An intramolecular spin of the LDL receptor beta propeller. Structure (London, England : 1993) 15 12575931
2017 Consistent hypersocial behavior in mice carrying a deletion of Gtf2i but no evidence of hyposocial behavior with Gtf2i duplication: Implications for Williams-Beuren syndrome and autism spectrum disorder. Brain and behavior 14 29568691
2012 Epigenetic modulation by TFII-I during embryonic stem cell differentiation. Journal of cellular biochemistry 14 22628223
2011 Role for transcription factor TFII-I in the suppression of SSeCKS/Gravin/Akap12 transcription by Src. International journal of cancer 14 20568114
2010 Trivinylphosphine and trivinylphosphine chalcogenides: stereochemical trends of ³¹P-¹H spin-spin coupling constants. Magnetic resonance in chemistry : MRC 14 21104762
2004 Spin anisotropy and slow dynamics in spin glasses. Physical review letters 14 15169256
2021 Interaction of Photogenerated Spin Qubit Pairs with a Third Electron Spin in DNA Hairpins. Journal of the American Chemical Society 13 33735563
2012 ChIP-Chip Identifies SEC23A, CFDP1, and NSD1 as TFII-I Target Genes in Human Neural Crest Progenitor Cells. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 13 23145914
2009 New TFII-I family target genes involved in embryonic development. Biochemical and biophysical research communications 13 19527686