Some of the TCF4 references on this page are not about "transcription factor 4 (TCF4)" but about "T-cell factor 4" with the same synonym (TCF4, or TCF7L2). Please help to remove these wrong references.

Disease relevance of TCF4

• Hemizygosity of TCF4 is one of the causes of Pitt-Hopkins   syndrome [1]. Multiple individuals are identified who have hemizygous deletions of all or a part of this gene. Penetrance is very high since no hemizygous individuals have been identified without this phenotype.
• Hedgehog (Hh) signaling restricts the expression of Wnt targets to the base of the colonic crypt in vivo, and transfection of Ihh into colon cancer cells leads to a downregulation of both components of the nuclear TCF4-beta-catenin complex and abrogates endogenous Wnt signaling in vitro [2].
• A colorectal carcinoma cell line, DLD-1, was engineered to suppress transactivation by the TCF4/beta-catenin complex in a dominant-negative manner under the strict control of the tetracycline regulatory system [3].
• Chromatin immunoprecipitation experiments in LNCaP prostate cancer cells showed that endogenous AR was bound to a Tcf4-responsive element in the c-myc promoter [4].
• HASH-1 and E2-2 are expressed in human neuroblastoma cells and form a functional complex [5].

Psychiatry related information on TCF4

• Analysis of genome-wide CAG/CTG repeats, and at SEF2-1B and ERDA1 in schizophrenia and bipolar affective disorder [6].
• ITF2 was found to directly bind to negative acting Id HLH proteins and positive acting bHLH proteins such as scleraxis [7].
• At present no strong evidence exists that large repeat alleles at either SEF2-1B or ERDA1 are involved in the etiology of schizophrenia or bipolar disorder [8].

High impact information on TCF4

• The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells [9].
• Thus, the beta-catenin/TCF-4 complex constitutes the master switch that controls proliferation versus differentiation in healthy and malignant intestinal epithelial cells [9].
• The TCF-4 target gene c-MYC plays a central role in this switch by direct repression of the p21(CIP1/WAF1) promoter [9].
• The complementary DNAs are the products of distinct genes, yet both ITF-1 and ITF-2 are structurally and functionally similar [10].

Chemical compound and disease context of TCF4

• Src-dependent activation of beta-catenin was prevented by SKI-606, a novel Src family kinase inhibitor, which also abrogated beta-catenin nuclear function by impairing its binding to the TCF4 transcription factor and its trans-activating ability in colorectal cancer cells [11].

Biological context of TCF4

• Coexpression of mammalian beta-cat with TCF4 or LEF1 results in nuclear accumulation of these proteins and a functional complex that activates reporter gene transcription from constructs containing leukocyte enhancer factor (LEF)/T cell factor (TCF) response elements [12].
• However, transfection experiments with dominant-negative (dn) TCF4 revealed a strong dependence of Flt3-ITD-mediated clonogenic growth on TCF activity [13].
• Transfection of TCF4 cDNA inhibited adipogenic differentiation, whereas a dominant negative TCF4 cDNA construct induced adipogenesis and blocked testosterone's inhibitory effects [14].
• Genetic and cellular characterizations of human TCF4 with microsatellite instability in colon cancer and leukemia cell lines [15].
• Here we describe for the first time a TCF4 MSI+ phenotype in leukemia cell lines except in colon cancer cell lines [15].

Anatomical context of TCF4

• In conclusion, E2-2 forms a functional complex with HASH-1, and might therefore be involved in the development of specific parts of the central and peripheral nervous systems [5].
• Wnt signalling, which is transduced through beta-catenin/TCF4, maintains the undifferentiated state of intestinal crypt progenitor cells [16].
• The loss of epithelial cell polarity may be a critical cellular event driving beta-catenin/TCF4-mediated intestinal tumorigenesis [17].
• By the use of a strict tetracycline-regulation system, we found that the continuous suppression of beta-catenin/TCF4-mediated gene transactivation by dominant-negative TCF4B (deltaN30) reduced these piled-up foci and restored a simple monolayer of polarized columnar cells resembling normal intestinal epithelium [17].
• So far, the combined status of beta-catenin and TCF4 and its relevance for lymph node metastasis and CD44 expression have not been well studied in gastric cancers (GCs) [18].

Associations of TCF4 with chemical compounds

• Furthermore, TCF4, which is one of the transcriptional factors in the Wnt signaling pathway and has a mononucleotide repeat sequence (a nine- adenine repeat, (A)9) in its C-terminal region, was mutated in 13 of the 33 samples [19].
• Furthermore, the ectopic expression of beta-catenin-TCF4 in cells that constitutively express low levels of the transactivation complex produces a significant increase of GLCE transcript level and, at the same time, enhances the rate of D-glucuronic acid epimerization in HS [20].
• In cells transfected with dominant negative CREB lithium-stimulated proliferation was unchanged whereas blocking Wnt/beta-catenin by dominant negative TCF4 reduced proliferation by approx. 50% [21].
• These include inhibition of, both the biochemical activation of ILK, inhibition of serine 9 GSK3beta phosphorylation and the enhancement of TCF-4 transcriptional activity [22].
• Ca(2+) strongly induced E-cadherin expression and inhibited the expression of the nuclear transcription factor, TCF4 [23].

Physical interactions of TCF4

• The HASH-1/E2-2 complex binds an E-box (CACCTG) in vitro, and transactivates an E-box containing reporter construct in vivo [5].
• Binding studies in solution and in heterogeneous phase showed that TCF4 binds reversibly to beta-catenin with an affinity (KB) of 3(+/-1) 10(8) M(-1) [24].

Regulatory relationships of TCF4

• 1,25(OH)(2)D(3) was weaker in its effect on E-cadherin and was not able to inhibit TCF4 expression [23].
• Heregulin induces expression, DNA binding activity, and transactivating functions of basic leucine zipper activating transcription factor 4 [25].

Other interactions of TCF4

• Furthermore, E2-2 seems to be one of the major HASH-1 interacting proteins in extracts from neuroblastoma cells [5].
• Phylogenetic analysis revealed four E protein branches among vertebrates: EX, E2A, HEB, and E2-2 [26].
• Single genes orthologous to HEB and to E2-2 were identified [26].
• This system consists of GAL4/beta-catenin, VP16/Tcf4, and a gene that is transcribed when GAL4 and VP16 associate [27].
• Here we report the identification of the matrix metalloproteinase MMP-7 as another target gene of beta-catenin/TCF-4 [28].

Analytical, diagnostic and therapeutic context of TCF4

• Electrophoresis mobility shift assay demonstrated that TCF4 and beta-catenin form a complex and have DNA binding activity [29].
• These differences may be attributable to an enhanced affinity of S37A beta-catenin for LEF1 and TCF4, as observed here by immunoprecipitation assays [30].
• Site-directed mutagenesis, together with calorimetric measurements, revealed that residue D16 in TCF4 plays a crucial role in high-affinity binding [24].
• We have characterized the binding of TCF4 to human beta-catenin by steady-state intrinsic fluorescence quenching experiments, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) [24].
• In this study, we performed Ala-scanning mutagenesis of all Tcf4 residues in the Tcf-beta-catenin interface and studied the binding energetics of these mutants using isothermal titration calorimetry [31].

References