Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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lymphoid enhancer binding factor 1(LEF1) lymphoid enhancer binding factor 1(LEF1) Related Genes Homo sapiens
CYTOBAND 4q23-q25,
GENERIF_SUMMARY Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling., MITF-M transactivates its own promoter (M promoter) by interacting with LEF-1, wnt3a-beta catenin signaling regulates LEF-1 gene expression, direct evidence for a role of beta-catenin/LEF-1 signaling pathway in induction of epithelial-mesenchymal transformation, ZEB1 plays a role in repressing E-cadherin and MUC1 in epithelial cells [ZEB-1], Nr-CAM is the gene most extensively induced by LEF1, induction of Lef/Tcf-dependent transcription in human endothelial cells by fibroblast growth factor-2, These results suggest that NLK phosphorylation on these sites contributes to the down-regulation of LEF-1/TCF transcriptional activity., Tcf/LEF1 has a role in transcriptional induction of cyclin D1, loss of expression of this transcription factor in a subset of peripheral t-cell lymphomas, Beta-catenin, Lef-1, Ets transcription factors, and the AP-1 protein c-Jun each weakly enhanced luciferase expression from an OPN promoter., Lymphoid enhancer factor/T cell factor has a role in development of colorectal cancer [review], Wnt regulation of the Lef-1 promoter at the WRE may play an important role during airway submucosal glandular bud formation., a 110 bp Wnt/beta-catenin-responsive element, contained within a minimal 2.5 kb Lef-1 promoter, plays an important role in regulating mesenchymal, and potentially epithelial, expression during follicle development in mouse embryos., LEF-1 expression is regulated through PITX2, LEF-1 and beta-catenin direct physical interactions, Smad-binding peptide aptamer LEF1 can be developed to selectively inhibit TGF-beta-induced gene expression., Taken together, these data suggest that LEF-1 is abundantly expressed in human tumors and the ratio of the oncogenic and the dominant negative short isoform altered not only in carcinomas but also in leukemia., LEF1 5'-untranslated region (UTR) mediates cap-independent translation; the 5'-UTR of full-length LEF1 mRNA contains a bona fide internal ribosome entry site (IRES)., LEF1, a downstream component of the Wnt signaling pathway, mediates breast cancer cell invasion, and may be regulated in part by estradiol, Involvement of LEF1 protein in the wingless type protein (WNT) signaling pathway not only regulates T cell development, but also peripheral T cell differentiation., hAR is a direct target of LEF-1/TCF transcriptional regulation in PCa cells; expression of the hAR protein is suppressed by a degradation pathway regulated by cross-talk of Wnt, Akt, and PP2A, Sebaceous gland neoplasms harbor inactivating mutations in LEF1., NARF functions as a novel ubiquitin-ligase to regulate ubiquitylation and degradation of T cell factor/lymphoid enhancer factor, the biological outcome of aberrant LEF1 activation in colon cancer is directed by differential promoter activation and repression, LEF-1 is an instructive factor regulating neutrophilic granulopoiesis whose absence plays a critical role in the defective maturation program of myeloid progenitors in individuals with congenital neutropenia, Cooperates with SMAD4 to activate c-myc expression., Additional prolactin (PRL) regulatory elements corresponding to LEF-l and AP-1 transcription factor binding sites appear important for PRL expression., LEF-1 is a decisive transcription factor in neutrophil granulopoiesis [review], This study demonstrates that the two consensus Lef/Tcf binding elements (TBE)reported in neoplastic cells are dispensable for c-Myc regulation in normal keratinocytes, which instead use a novel TBE sequence variant., Notch1 co-opts Lef1 during the process of transformation to maintain survival of T-cell lymphomas, Re-expression of E-cadherin in HT29(US) cells restored the ability of caveolin-1 to down-regulate beta-catenin-Tcf/Lef-dependent transcription and survivin expression, as seen in HT29(ATCC) cells., These data support a role for PITX2 in cell proliferation, migration, and cell division through differential Lef-1 isoform expression and interactions with Lef-1 and beta-catenin., Marked upregulation of lymphoid enhancer-binding factor 1 (LEF-1), a transcription factor in the Wnt pathway, was found in HBsAg-expressing cells, role of Lef-1 in the biology of acute leukemia, pointing to the necessity of balanced Lef-1 expression for an ordered hematopoietic development, IL-4 stimulation possesses a negative effect on the expressions of LEF-1 and TCF-1 in primary T cells, suggesting a positive feedback effect of IL-4 on IL4 gene expression., beta-catenin acts together with Lef-1 to influence DeltaNp63 promoter activity and protein expression, Dpr1 negatively modulates the basal activity of Wnt1/beta-catenin signaling in the nucleus by keeping LEF1 in the repressive state., Id-1 is a novel PTEN inhibitor that could activate the Akt pathway and its downstream effectors, the Wnt/TCF pathway and p27(Kip1) phosphorylation, GnRH regulation of Jun transcription requires a functional interaction between TCF/LEF and beta-catenin., By reducing COX-2 expression, caveolin-1 interrupts a feedback amplification loop involving PGE(2)-induced signaling events linked to beta-catenin/Tcf/Lef-dependent transcription of tumor survival genes including cox-2 itself and survivin., LEF1 is a potential marker for androgen-independent disease and a key regulator of AR expression and prostate cancer growth and invasion. LEF1 is highly expressed in androgen-independent prostate cancer., hepatitis B surface antigen could stimulate proliferation and functional modification of hepatocytes via LEF-1 through the Wnt pathway at the pre-malignant stage, Two WNT target genes, LEF1 and HOXB9, are identified as promoters of lung adenocarcinoma metastasis and mediators of chemotactic invasion and colony outgrowth., expression of alternatively spliced Lef-1 isoforms is involved in the determination of proliferative or migratory characteristics of pancreatic carcinoma cells., Data show that elevated Snail expression by Pdcd4 knockdown leads to downregulation of E-cadherin resulting in activating beta-catenin/Tcf-dependent transcription., EWS/FLI1 binds LEF1, interfering with the formation of beta-catenin-LEF1 complexes, and thus with their transcriptional activity., LEF1 inactivation is an important step in the molecular pathogenesis of T-ALL in a subset of young children., LEF-1 binds specifically to the major histocompatibility complex class I-like protein CD1D promoter; enhanced expression of LEF1 in K562 or Jurkat cells suppresses CD1D promoter activity and downregulates endogenous CD1D transcripts., This study identified aberrant protein expression of LEF-1 specifically in chronic lymphocytic leukemia but not in normal mature B-cell subsets or after B-cell activation., LRP6-ICD interacts with AES exclusively in the nucleus and represses AES mediated TCF/LEF-1 reporter transcription., PC3 tumors are sustained by a small number of tumor-initiating cells with stem-like characteristics, including strong self-renewal and pro-angiogenic capability and marked by the expression pattern FAM65Bhigh/MFI2low/LEF1low., Lef1DeltaN binds beta-catenin, stimulates Lef/Tcf reporter activity, and promotes terminal osteoblast differentiation., HIPK2-dependent phosphorylation caused the dissociation of LEF1, TCF4, and TCF3 from a target promoter in vivo., Overexpression of LEF1 in primary colorectal carcinoma is a prognostic factor for poor survival and increased risk for liver metastasis., Alternative splicing of LEF1 exon 6 is regulated during pre-TCR signaling in thymic development and in response to activation of the JSL1 T-cell line and this is driven by the activity of CELF2., a novel interaction between the VDR and LEF1 that is mediated by the DNA-binding domain of the VDR and that is required for normal canonical Wnt signaling in keratinocytes., lymphoid enhancer-binding factor 1 identifies androgen-independent epithelium in the developing prostate, A strong promoter activity of pre-B cell stage-specific Crlz1 gene is caused by one distal LEF-1 and multiple proximal Ets sites., Melanoma cell phenotype switching behaviour is regulated by differential LEF1/TCF4 activity., Report universal nuclear overexpression of LEF1 but lack of nuclear beta-catenin in the majority of chronic lymphocytic leukemia/small lymphocytic lymphomas., An association between the maternal genotype and the occurrence of cleft lip or palate was observed at two polymorphic loci (rs10022956 and rs10025431), while a foetal-maternal effect modulating the risk of clefting was found at locus rs10025431., identification of a variable number of tandem repeats polymorphism in IDO1 promoter and characterization of LEF-1 response elements, differentiation status of chronic lymphocytic leukemia (CLL) cells would result in loss of LEF-1 expression, The study demonstrated a novel b-catenin/ LEF1-miR-372&373-Dickkopf-1 regulatory feedback loop, which may have a critical role in regulating the activity of Wnt/b-catenin signaling in human cancer cells., In this review we present mounting evidence for the interdependency of TCF7/LEF1 variant expression and functions with cell lineage and cell state. [Review], nuclear IGF1R associates with the transcription factor LEF1 and increases promoter activity of LEF1 downstream target genes cyclin D1 and axin2., a robust transcriptional CTNNAL1 up-regulation occurs during acute ozone-induced stress and is mediated at least in part by ozone-induced recruitments of LEF-1 and AP-2alpha to the human CTNNAL1 promoter., findings suggest that transcriptional activation of LEF1 is a mechanism of cross talk between HGF/c-Met and Wnt/beta-catenin pathways and is essential for HGF-induced tumor invasion, results suggest that assessing intracellular beta-catenin and LEF1 expression might help in patient risk stratification and outcome prediction, LEF-1 might play an important role in colon carcinogenesis by acting as a regulator., our results indicate a pivotal role of LEF-1 in the regulation of proliferation and MMP-7 transcription in breast cancer cells., miR-218 is involved in the invasive behavior of glioblastoma cells by targeting LEF1 and blocking the invasive axis., this study demonstrated that miR-449a directly targets LEF-1, which in turn affects the expression of Sox 9, ultimately leading to the proper regulation of the differentiation and chondrogenesis, Lef1 is overexpressed in human endometrial tumors, consistent with it playing a role in gland proliferation., High LEF1 expression is associated with significantly better relapse-free survival, overall survival, and event-free survival of cytogenetically normal acute myeloid leukemia patients., n-Butyl benzyl phthalate promotes breast cancer progression by inducing expression of lymphoid enhancer factor 1, interaction of HCLS1 with LEF-1 is essential for G-CSF-triggered myeloid differentiation, Results suggest that NDRG2 and prenylated Rab acceptor-1 (PRA1) might act synergistically to prevent signaling of T-cell facto/beta-catenin., Nuclear LEF1 correlate with cerebral metastasis of lung adenocarcinomas., DNA-dependent protein kinase catalytic subunit is a novel interaction partner of lymphocyte enhancer factor 1., This study supports a functionally important role for LEF1 and its target genes in Burkitt's lymphoma., Studied the expression of TCF/LEF and SFRP family members (SFRP1 and SFRP3) to gain a better understanding of biological signaling pathways responsible for epidemiology and clinical parameters of clear cell RCC (cRCC)., Results indicate that lymphoid enhancer-binding factor 1 (LEF1) contributes to the pathophysiology of acute myeloid leukemia (AML) and could be a predictor of better treatment response., High LEF1 expression is associated with prostate cancer., Our study suggests LEF1 expression in oral squamous cell carcinoma may play an important role in tumor progression and can be served as a predictor of poor prognosis for patients with oral squamous cell carcinoma., LEF1 protein was overexpressed in colon cancer tissues and knockdown of LEF1 expression inhibited colon cancer growth in vitro and in vivo., LEF1 expression is an independent prognostic factor in APL, and could be used in patients risk stratification., By beta-catenin's association with LEF1 and BCL9-2/B9L., Selenite caused CYLD upregulation via LEF1 and cIAP downregulation, both of which contribute to the degradation of ubiquitin chains on RIP1 and subsequent caspase-8 activation and colorectal tumor cell apoptosis., These results further implicate the CTNNB1/LEF1 transcriptional complex in the development of solid-pseudopapillary neoplasms of the pancreas, miR26b may act as a potential therapeutic agent in reducing cancer cell proliferation through repressing LEF1 activation of c-Myc and cyclin D1 expression, Tcf1 and Lef1 cooperate with Runx factors to achieve stable silencing of the Cd4 gene in CD8(+) T cells., Elevated TCF-1 and LEF-1 expression is characteristic of malignant gliomas, the expression of LEF1 is associated with the progression of human renal cell carcinoma and LEF1 maybe involved in the development of RCC, Increased expression of beta-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 is significantly correlated with decreased survival and poor prognosis in acral melanoma., LEF-1 expression is associated with the presence of KRAS mutations and may have prognostic value as a trend of worse overall survival is seen in patients with LEF-1-positive colorectal carcinoma., LEF-1 expression in both basal cell adenomas and basal cell adenocarcinomas preferentially over other salivary gland tumors suggesting some utility as a diagnostic marker, Study found a negative correlation between miR-34a and LEF1 expression in prostate cancer cell lines and tumors and that miR-34a regulated epithelial-mesenchymal transition through direct binding to LEF1 mRNA 3' UTR region and silencing its translation., Proper sample processing ensured sufficient separation of positive LEF1 staining in T cells from negative staining in normal B and natural killer (NK) cells, The results describe a novel mutation in LEF1 causing dysregulation of Wnt/B catenin signaling in eyelid sebaceous cancinoma, study identified TCF1 and LEF1 as Tax antagonistic factors in vivo, a fact which may critically influence the peripheral T-cell tropism of this virus, Authors found that the N-terminus of delta-catenin bound to the middle region of LEF-1 unlike beta-catenin. Overexpressed delta-catenin entered the nucleus and inhibited LEF-1-mediated transcriptional activity in Bosc23 and DLD-1 cell lines., high LEF1 expression and mutation are associated with high-risk leukemia and our results also revealed that LEF1 high expression and/or gain-of-function mutations are involved in leukemogenesis of ALL., Overexpression of LEF1 is a favorable prognostic factor in childhood ALL., Methylprednisolone can suppress Wnt signaling pathway by down-regulating LEF-1 protein expression in chronic lymphocyte leukemia cells., LEF-1 and MITF regulate tyrosinase gene transcription in vitro via binding to its promoter., The results suggest a role for beta-catenin/LEF1-mediated transcription in both malignant transformation and metastasis of prostate cancer,
OMIM_DISEASE Sebaceous tumors, somatic,
SP_COMMENT alternative products:Additional isoforms seem to exist, domain:Proline-rich and acidic regions are implicated in the activation functions of RNA polymerase II transcription factors., function:Participates in the Wnt signaling pathway. Activates transcription of target genes in the presence of CTNNB1 and EP300. May play a role in hair cell differentiation and follicle morphogenesis. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by LEF1 and CTNNB1. Regulates T-cell receptor alpha enhancer function. Binds DNA in a sequence-specific manner. PIAG antagonizes both Wnt-dependent and Wnt-independent activation by LEF1 (By similarity). Isoform 3 lacks the CTNNB1 interaction domain and may be an antagonist for Wnt signaling., similarity:Belongs to the TCF/LEF family., similarity:Contains 1 HMG box DNA-binding domain., subcellular location:Found in nuclear bodies upon PIASG binding., subunit:Binds the armadillo repeat of CTNNB1 and forms a stable complex. Interacts with EP300, TLE1 and PIASG (By similarity). Binds THOC4, MDFI and MDFIC., tissue specificity:Detected in thymus. Not detected in normal colon, but highly expressed in colon cancer biopsies and colon cancer cell lines.,
transcription factor 7 (T-cell specific, HMG-box)(TCF7) transcription factor 7 (T-cell specific, HMG-box)(TCF7) Related Genes Homo sapiens
CYTOBAND 5q31.1,
GENERIF_SUMMARY beta-catenin and TCF inversely control the expression of the EphB2/EphB3 receptors and their ligand ephrin-B1 in colorectal cancer and along the crypt-villus axis., A polymorphism in ths gene, C883A, is associated with type 1 diabetes., Enforced expression of TCF-1 in transgenic mice yields an expanded Ly-49A subset of natural killer (NK) cells; TCF-1 regulates stable induction of Ly-49A gene expression by formation of a nucleoprotein complex at the Ly-49A promoter., TCF1 is phosphorylated and inhibited by Wnt signal transduction through the Tak1 pathway, Ly-49A effectively limits Ag-driven T cell proliferation, cytokine production, and changes in surface receptor expression, and effectively limits Ag-specific CD4 cell responses even in the presence of sustained autoantigen expression in vivo, Involvement of transcription factor 7 (T cell factor-1) in the wingless type protein (WNT) signaling pathway not only regulates T cell development, but also peripheral T cell differentiation., TCF7 is involved in genetic risk to Type I Diabetes, although the associations observed for both the intronic SNP rs17653687 and the nonsynonymous change encoded by rs5742913 are relatively modes., Data show that upon HIPK2-mediated phosphorylation, TCF3 is replaced with positively acting TCF1 at a target promoter., Transgenic T cell factor 1 (TCF1) binds to regulatory regions of the IL17 gene and directly regulates IL17A and IL17F gene expression., Findings demonstrate that t-DARPP regulates beta-catenin/TCF activity, thereby implicating a novel oncogenic signaling in upper gastrointestinal cancers., Results suggest that Tcf-1 may contribute to pathogenesis of acquired aplastic anemia by regulating downstream gene expression such as c-myc and CD44., In this review we present mounting evidence for the interdependency of TCF7/LEF1 variant expression and functions with cell lineage and cell state. [Review], in this review, we will focus on the function of beta-catenin/TCF-1 pathway in the regulation of thymic and peripheral T cell differentiation processes--{REVIEW}, The repression of syndecan-2 by Wnt/beta-catenin/TCF signaling contributes to the resistance of osteosarcoma cells to doxorubicin., findings show that induction of a dominant negative C-clamp version of TCF1 (dnTCF1E) induces p21 expression and a stall in the growth of DLD1 colon cancer cells; results indicate that a rapid-response WNT/p21 circuit is driven by C-clamp target gene selection, Studied the expression of TCF/LEF and SFRP family members (SFRP1 and SFRP3) to gain a better understanding of biological signaling pathways responsible for epidemiology and clinical parameters of clear cell RCC (cRCC)., we establish that ATF2 family members physically and functionally interact with TCF1/LEF1 factors to promote target gene expression and hematopoietic tumor cell growth, miRNAs inhibited the expression of the luciferase reporter constructs containing 3'UTRs of these genes and downregulated protein expression of TERT and the TCF7 transcription factor, which mediates the canonical Wnt pathway., Results suggest ivermectin as therapeutic WNT protein-TCF transcription factor pathway response blocker to treat WNT-TCF-dependent diseases including multiple cancers., we show that TCF7 is a direct target of miR-34a in prostate cancer that has metastasized to the bone, RUNX2 signaling pathways with their partners TCF7 and FGFR1/2 may not be involved in CCD pathogenesis, induction of expression activates the Wnt signaling pathway, leading to priming of liver cancer stem cells self-renewal and tumor propagation, Capsaicin-induced apoptosis in pancreatic cancer cells was associated with inhibition of beta-catenin signaling due to the dissociation of beta-catenin/TCF-1 complex and the process was orchestrated by STAT-3., Findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent "metastatic founder cells" which have invasive properties., TCF7 plays critical roles in lung diseases [review], Tcf7 levels are lower in islets taken from patients with type 2 diabetes. Knockdown of TCF7 in islets impairs the cytoprotective responsiveness to GIP and enhances the magnitude of apoptotic injury.,
SP_COMMENT alternative products:2 series of isoforms, L and S, are produced by use of alternative promoter usage. Additional isoforms seem to exist, function:Transcriptional activator involved in T-cell lymphocyte differentiation. Necessary for the survival of CD4(+) CD8(+) immature thymocytes. Isoforms lacking the N-terminal CTNNB1 binding domain cannot fulfill this role. Binds to the T-lymphocyte-specific enhancer element (5'-WWCAAAG-3') found in the promoter of the CD3E gene. May also act as feedback transcriptional repressor of CTNNB1 and TCF7L2 target genes. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7 and CTNNB1., induction:By TCF7L2 and CTNNB1., sequence caution:Wrong choice of frame., similarity:Belongs to the TCF/LEF family., similarity:Contains 1 HMG box DNA-binding domain., subunit:Binds the armadillo repeat of CTNNB1 and forms a stable complex. Interacts with AES, TLE1, TLE2, TLE3 and TLE4., tissue specificity:Predominantly in T-cells. Also detected in proliferating intestinal epithelial cells and in the basal epithelial cells of mammary gland epithelium.,
transcription factor 7 like 1(TCF7L1) transcription factor 7 like 1(TCF7L1) Related Genes Homo sapiens
CYTOBAND 2p11.2,
GENERIF_SUMMARY No difference in nuclear beta-catenin signal intensity was found, which may be caused by an alteration in Wnt pathway in microsatellite stable sporadic tumors by unknown mechanisms leading to lower TCF-3, 4 protein expression., Data indicate that median methylation levels of BCAN, HOXD1, KCTD8, KLF11, NXPH1, POU4F1, SIM1, and TCF7L1 were >/=30% higher than in normal samples, representing potential biomarkers for tumor diagnosis., report the identification of two independent missense variants in human TCF7L1, p.R92P and p.R400Q, in a cohort of patients with forebrain and/or pituitary defects,
SP_COMMENT domain:The putative Groucho interaction domain between the N-terminal CTNNB1 binding domain and the HMG-box is necessary for repression of the transactivation mediated by TCF7L1 and CTNNB1., function:Participates in the Wnt signaling pathway. Binds to DNA and acts as a repressor in the absence of CTNNB1, and as an activator in its presence. Necessary for the terminal differentiation of epidermal cells, the formation of keratohyalin granules and the development of the barrier function of the epidermis (By similarity). Down-regulates NQO1, leading to increased mitomycin c resistance., similarity:Belongs to the TCF/LEF family., similarity:Contains 1 HMG box DNA-binding domain., subunit:Binds the armadillo repeat of CTNNB1 and forms a stable complex., tissue specificity:Detected in hair follicles and skin keratinocytes, and at lower levels in stomach epithelium.,
transcription factor 7 like 2(TCF7L2) transcription factor 7 like 2(TCF7L2) Related Genes Homo sapiens
CYTOBAND 10q25.3,
GENERIF_SUMMARY tcf4 can specifically recognize beta-catenin using alternative conformations, crystal structure of a human Tcf4-beta-catenin complex; comparison with recent structures of beta-catenin in complex with Xenopus Tcf3 (XTcf3) and mammalian E-cadherin, Promoter characterization of the novel human matrix metalloproteinase-26 gene, Activation of AXIN2 expression by beta-catenin-T cell factor, ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with beta-catenin defects and promotes neoplastic transformation, role of TCF-4 upon transcription of the human immunodeficiency virus type 1 (HIV-1) promoter in human astrocytic cells, The high expression level of hTcf-4 in HCC, especially with metastasis, suggests that the over-expression of hTcf-4 gene may be closely associated with development and progression of HCC, but the mutation of this gene plays a less important role, disruption of beta-catenin/TCF-4 activity in CRC cells induces a rapid G1 arrest and blocks a genetic program that is physiologically active in the proliferative compartment of colon crypts., the C terminus of TCF4E cooperates with beta-catenin and p300 to form a specialized transcription factor complex that specifically supports the activation of the Cdx1 promoter, there is a direct interaction between the androgen receptor DNA binding domain (DBD) and Tcf4., TCF-4N inhibits coactivation by beta-catenin of TCF/LEF transcription factors and potentiates the coactivation by beta-catenin of other transcription factors, such as SF-1 and C/EBPalpha, TCF4 could be an effective therapeutic target for suppressing the growth of hepatocellular cancers., TCF4-binding element was identified in PTTG promoter region in eesophageal squamous cell sscarscinomsa., identify selective beta-catenin binding hot spots of Tcf4, E-cadherin, and APC, Together, we suggest that quercetin is an excellent inhibitor of beta-catenin/Tcf signaling in SW480 cell lines, and the reduced beta-catenin/Tcf transcriptional activity is due to the decreased nuclear beta-catenin and Tcf-4 proteins., TCF4 expression mediated by beta-catenin/p300 may be important for initial steps during trans-differentiation of endometrial carcinoma cells., The regulation of GLCE expression by 2 cis-acting elements of the beta-catenin-TCF4 complex located in the enhancer region of the promoter are reported., characterization of the TCF4 with microsatellite instability (MSI) in colon cancer and leukemia cell lines; results delineate a novel role for MSI+TCF4 in leukemia and colon cancer progression, the phosphorylation-dependent interaction between c-Jun and TCF4 regulates intestinal tumorigenesis by integrating JNK and APC/beta-catenin, two distinct pathways activated by WNT signalling, TIS7, a negative regulator of transcriptional activity, represses expression of OPN and beta-catenin/Tcf-4 target genes, The positive inter-regulation between beta-cat/Tcf-4 signaling and ET-1 signaling potentiates proliferation and survival of prostate cancer (CaP) cells, thereby representing a novel mechanism that contributes to CaP progression., results suggest an established Wnt signaling pathway in most gastric cancers, a close correlation of beta-catenin/TCF4-mediated signaling with tumor dissemination, and the unlikelihood of a direct effect of activated Wnt signaling on CD44 expression, Suggestive linkage of type 2 diabetes mellitus to TCFL2 protein on chromosome 10q., Represses Wnt signaling in breast tissue, and its downregulation contributes to the activation of Wnt signaling., A role is suggested for TCF7L2 frameshift mutation during MSI-H colorectal tumor progression, by regulating the relative proportion of the different TCF7L2 isoforms., Daxx reduced DNA binding activity of Tcf4 and repressed Tcf4 transcriptional activity., findings suggest that activity at the HIV-1 promoter is influenced by phosphorylation of Sp1, which is affected by Tat and DNA-PK; interactions among TCF-4, Sp1 and/or Tat may determine the level of viral gene transcription in astrocytic cells, evidence provided that HIC1 antagonizes the TCF/beta-catenin-mediated transcription in Wnt-stimulated cells; this appears to be due to the ability of HIC1 to associate with TCF-4 and to recruit TCF-4 and beta-catenin to the HIC1 bodies, Common variants (rs12255372 and rs7903146) in TCF7L2 seem to be associated with an increased risk of diabetes among persons with impaired glucose tolerance, These data provide replicating evidence that variants in TCF7L2 increase the risk for type 2 diabetes and novel evidence that the variants likely influence both insulin secretion and insulin sensitivity., These results suggest that TCF7L2 variants may act through insulin secretion to increase the risk of type 2 diabetes., These data provide evidence that TCF7L2 is a major determinant of type 2 diabetes risk in European populations and suggests that this transcription factor plays a key role in glucose homeostasis., Combining information from several known common risk polymorphisms allows the identification of population subgroups with markedly differing risks of developing type 2 diabetes compared to those obtained using single polymorphisms., Variants of the TCF7L2 gene contribute to the risk of type 2 diabetes. The population-attributable risk from this factor in the Dutch type 2 diabetes population is 10%., crystallographic analysis of how beta-catenin, BCL9, BCL9-2 and Tcf4 interact, Although TCF7L2 is a major gene in type 2 diabetes, there is no evidence for association between this gene and type 1 diabetes., TCF7L2 T at-risk allele variation predicts hyperglycemia incidence in a general French population, possibly through a deleterious effect on insulin secretion., A high mobility group box-containing TCF7L2 leads to diabetes risk., No major contribution of TCF7L2 sequence variants to maturity onset of diabetes of the young (MODY) or neonatal diabetes mellitus was found in this study in French white subjects., TCF7L2 is an important gene for determining susceptibility to type 2 diabetes mellitus and it transgresses the boundaries of ethnicity., results suggest a possible influence of TCF7L2 rs12255372 on the risk of familial breast cancer, TCF7L2 gene is an important factor regulating insulin secretion, which could explain its association with type 2 diabetes., AXIN1, AXIN2 and TCF7L2 may have roles in development of colorectal carcinomas [review], polymorphism is associated with lower insulin levels, smaller waist circumference, and lower risk lipid profiles in the general elderly population., TCF7L2 variants increase type 2 diabetes risk and may affect pancreatic beta cell function., Several single nucleotide polymorphisms are associated with type 2 diabetes., TCF7L2 is a common susceptibility gene for type 2 diabetes in the Japanese population, data provide evidence that variation in the TCF7L2 genomic region may affect risk for type 2 diabetes in Mexican Americans, but the attributable risk may be lower than in Caucasian populations, Variation in TCF7L2 is associated with gestational diabetes and interacts with adiposity to alter insulin secretion in Mexican Americans., May be a strong candidate for conferring susceptibility to type 2 diabetes across different ethnicities in Japan., Variant is associated with an increased risk of gestational diabetes mellitus in Scandinavian women., combined effect of obesity and genotype in predicting type 2 diabetes risk in a sample of French Canadian cardiac patients. in predicting type 2 diabetes risk in a sample of French Canadian cardiac patients., Transcription factor 4 (TCF-4), the downstream effector of Wnt signaling, is implicated in repressing HIV replication in astrocytes., findings suggest that the TCF7L2 risk allele may predispose to type 2 diabetes by impairing beta-cell proinsulin processing, Variants of TCF7L2 may be associated with increased disease severity and therapeutic failure in diabetes., A cariant of TCF7L2 is associated with incident type 2 diabetes in a separate population-based cross-sectional study., evaluated the association of the three TCF7L2 polymorphisms with NIDDM by using the program admixmap to fit a logistic regression model incorporating individual ancestry, sex, age, body mass index and education, Study assessed role of TCF4 in birth weight., TCF7L2 variants influence therapeutic response to sulfonylureas but not metformin, an increased risk of type 2 diabetes is associated with TCF7L2 rs7903146 genotype., The discovery of TCF7L2 as a diabetes gene illustrates that novel true diabetes genes can be found, their association with type 2 diabetes replicated and their effect incorporated into risk prediction models (Review), TCF7L2 genetic polymorphisms are major determinants for risk of type 2 diabetes in the Chinese population., Results confirmed TCF7L2 as a risk factor in a population of European descent, where it reduced glucose tolerance and insulin sensitivity, but not insulin secretion., TCF7L2 rs7903146 variant neither increases the risk for SGA nor modulates birth weight and young adulthood glucose homeostasis in French Caucasian subjects born with SGA, Variations in the TCF7L2 gene significantly contribute to diabetes susceptibility in African-American populations., Variations at TCF7L2 contribute to Type 2 diabetes., Odds ratio for single nucleotide polymorphisms associated with plasma proinsulin, beta cell dysfunction and increased risk of type 2 diabettes., Novel mutations in exon 4 of hTCF-4 gene were revealed in this study, which might be of importance in the pathogenesis of sporadic rectal cancer patients with high frequency microsatellite instability., Variants of TCF7L2 specifically impair GLP-1-induced insulin secretion., Common variants in the TCF7L2 gene and its predisposition to type 2 diabetes in UK European Whites, Indian Asians and Afro-Caribbean men and women are reported., the increased risk of type 2 diabetes conferred by variants in TCF7L2 involves the enteroinsular axis, enhanced expression of the gene in islets, and impaired insulin secretion., TCF7L2 does not participate in the etiology of Type 1 diabetes, The genetic susceptibility from the TCF7L2 gene variation is a unique mechanism of type 2 diabetes (T2D), and is not shared by type 1 diabetes (T1D)., The rs12255372(G/T) and rs7903146(C/T) polymorphisms of TCF7L2 gene confer susceptibility to type 2 diabetes mellitus in Asian Indians., A reduced expression in ileal Crohn's disease of the Wnt-signaling pathway transcription factor Tcf-4, a known regulator of Paneth cell differentiation and alpha-defensin expression, was reported., common variation in the TCF7L2 gene contributes to Type 2 diabetes risk in UK patients recruited in general practice, but the risk allele frequency may be lower than that in subjects enriched for genetic effects, Overexpression of TCF-4 is associated with the development of lung cancer, Establishing whether variation in TCF7L2 also influences the development of polycystic ovary syndrome and type 2 diabetes., Data indicate that Sox4 and 17 can act as both antagonists and agonists of beta-catenin/TCF activity, and this mechanism may regulate Wnt signaling responses in many developmental and disease contexts., TCF7L2 (transcription factor 7-like 2) has been identified as a gene for type 2 diabetes., Variation within TCF7L2 does not confer major risk for type 2 diabetes among the Pima Indian population., TCF7L2 rs7903146 genetic variation is associated with an increased risk of post transplantation diabetets mellitus in renal allograft recipients., TCF7L2 variants could play a role in the pathogenesis of type 2 diabetes mellitus in the Hispanic American population through a mchanism involving insulin secretion., TCF7L2 is associated with high serum triacylglycerol and differentially expressed in adipose tissue in families with familial combined hyperlipidaemia, Topo IIalpha interacts with beta-catenin/T-cell factor-4 as a novel transcriptional co-activator in colorectal neoplasms., MTG family members associate specifically with TCF4. Coexpression of beta-catenin disrupted the association between these corepressors and TCF4., Ectopic expression of Dkk3 in lung cancer cells with Dkk3 hypermethylation induced apoptosis and inhibited TCF-4 activity, The role of TCF7L2 in beta-cell function and survival in cultured cells is reported., DG10S478 variant seems to have no influence on manifestation of diabetes and the development of microvascular complications., Single nucleotide polymorphisms in TCF7L2 were associated with type 2 diabetes, A precise and reproducible electrophoretic technique is used to make an allelic assignment from genomic DNA of the polymorphism in microsatellite DG10S478 of TCF7L2., myostatin enhanced nuclear translocation of beta-catenin and formation of the Smad3-beta-catenin-TCF4 complex, together with the altered expression of a number of Wnt/beta-catenin pathway genes in hMSCs, TCF7L2 is not a risk factor for obesity in European populations, but its effect on type 2 diabetes risk is modulated by obesity., Diabetes-associated variants in TCF7L2 and CDKAL1 impair insulin secretion and conversion of proinsulin to insulin., TCF4-binding regions significantly correlate with Wnt-responsive gene expression profiles derived from primary human adenomas, Subjects who were initially cancer-free and carrying certain genetic variants of TCF7L2 have an increased risk of colon cancer., TCF7L2 variants are associated with increased risk for diabetes mellitus in Emirati subjects., TCF7L2 rs7903146 T allele is present in obese hypertensive patients as much as in the general population., TCF7L2 is an important genetic risk factor for the development of type 2 diabetes in multiple ethnic groups, The TCF7L2 gene may alter risk of developing more aggressive prostate cancer., TCF7L2 mRNA levels in adipocytes are decreased by insulin and seem to increase in insulin resistant subjects and in HapA carriers., We confirm that c-Jun functions in canonical Wnt signaling and show that c-Jun functions as a scaffold in the beta-catenin-TCFs transcription complex bridging Dvl to TCF., TCF7L2 gene is a major risk factor for development of T2DM in Khatri Sikhs from North India., These data suggest that colon cancer risk associated with the rs7903146 TCF7L2 polymorphism is modified by use of aspirin/NSAIDs, Increased health risk associated with an rs7903146 genotype is specific to mortality in diabetes and diabetic angiopathies., Determination of role nuclear pore complex in regulating TCF4/beta cateninin mediated Wnt signaling., Data show that one TCF7L2 SNP (rs7903146) showed compelling evidence of association with type 2 diabetes in African Americans., association of TCF7L2 with type 2 diabetes [review], Data confirmed the associations of single nucleotide polymorphisms in TCF7L2 with risk for type 2 diabetes in Asians., there was suggestive evidence for an inverse association associated of colorectal cancer and ademoma with homozygosity for the minor allele of RS12255372 (TCF7L2 TT) and conditional and covariate adjusted risk 0for heterogeneity for in women and men, we did not find any mutation in the coding sequence of TCF7L2 that confers a genetic risk for type 2 diabetes in a Chinese population, results indicate that Tcf-4 maintains low levels of claudin-7 at the bottom of colonic crypts, acting via Sox-9, genetic variants in TCF7L2 confer a strong risk of future type 2 diabetes possibly mediated by altering expression of TCF7L2 in pancreatic islets [review], The higher homeostasis model assessment insulin resistance index (HOMA-B%) index in TT-homozygotes indicates TCF7L2 to be a susceptibility gene for the development of impaired glucose tolerance in obese children., Gene variants of CDKAL1, PPARG, IGF2BP2, HHEX, TCF7L2, and FTO predispose to type 2 diabetes in the German KORA 500 K study population., TCF7L2 SNPs revealed a significant association with type 2 diabetes, Summarize recent findings demonstrating the association between TCF7L2 polymorphisms and the risk of type 2 diabetes, outline experimental evidence of the potential function of TCF7L2 in pancreatic and intestinal endocrine cells. Review., The primary defect of rs7903146 T-allele carriers is impairment of insulin secretion rather than a defect in insulin action in peripheral tissues., the presumed cancer-promoting gene TCF7L2 functions instead as a transcriptional repressor that restricts colorectal cancer (CRC) cell growth., variants in the TCF7L2 gene are associated with reduced kidney function and CKD progression, Our study is consistent with weak or no association of type 2 diabetes in Arabs with the two TCF7L2 variants, Study show that polymorphisms in TCF7L2 were associated with type 2 diabetes risk in the studied population., TCF7L2 mRNA expression is fat-depot specific but does not seem to provide the mechanistic link explaining genetic association with type 2 diabetes mellitus., co-existence of TCF7L2 variants and the SPINK1 and CTSB mutations, that predict susceptibility to exocrine damage, may interact to determine the onset of diabetes in TCP patients, Evidence that the TCF7L2 gene is a major determinant of type 2 diabetes risk in Spain, as in other southern Eutopean populations., Frameshift mutations of Wnt pathway genes AXIN2 and TCF4 in gastric carcinomas with high microsatellite instability are reported., Results found a negative allele-dosage effect of the T allele of rs7903146 in the TCF7L2 gene on the changes in the HOMA-IR, the insulin sensitivity check index QUICKI and insulin secretion index HOMA-B% during a lifestyle intervention., Snail and Slug promote formation of beta-catenin-T-cell factor (TCF)-4 transcription complexes that bind to the promoter of the TGF-beta3 gene to increase its transcription, In morbidly obese nondiabetic patients, there was a positive correlation between TCF7L2 expression and BMI (R(2)=0.21)., Common variants in the TCF7L2 gene help to differentiate young but not middle-aged glutamic acid decarboxylase antibodies(GADA)-positive and GADA-negative diabetic patients, Sudy provides the first significant evidence of association between the TCF7L2 rs7903146 polymorphism and type 2 diabetes risk in a large African American population., The rs7903146 variant of the TCF7L2 gene might influence PCOS predisposition, while no association is observed between the E23K variant of KCNJ11 and susceptibility to PCOS and related traits., Risk alleles of the TCF7L2 gene showed increased risk of diabetes even when controlled for traditional diabetes risk factors, Increased expression in colorectal adenomas than in the adjacent normal epithelia, An assay using unlabeled probes and the LightCycler or Rotor-Gene instruments was developed for genotyping of PPARG, PPARGC1A and transcription factor 7-like 2 (TCF7L2) polymorphisms., Common coding variant in the TCF7L2 gene is associated with type 2 diabetes., Type 2 diabetes susceptibility of TCF7L2 was confirmed in Japanese., TCF7L2 type 2 diabetes susceptibility alleles are associated with islet autoantibody-negative but not autoantibody-positive new onset diabetes in young patients., Located on chromosome 10 and suscptibility of polymorphisms are related to type 2 diabetes., TCF7L2 rs7903146 T allele is associated with a 1.57 increased risk for type 2 diabetes in a Brazilian cohort of patients with known coronary heart disease, Genes implied in human type 2 diabetes development, TCF7L2, WFS1, FTO, SLC30A8, and GCKR, were mapped on Sus scrofa chromosomes 14, 8, 6, 4, and 3, respectively. Only TCF7L2 was significantly associated with five fat traits in pigs., TCF7L2 CT/TT genotype is more frequent in nonalcoholic fatty liver disease and predicts the presence and severity of liver disease., BCL-W may function as a downstream effector of inappropriate WNT/beta-catenin signalling., TCF4 regulates BIRC5 gene expression, High polyunsaturated fatty acid intakes were associated with atherogenic dyslipidemia in carriers of the minor T allele at the TCF7L2 single nucleotide polymorphism., the inverse association between whole-grain consumption and type 2 diabetes risk might depend on variation in TCF7L2., TCF7L2 gene expression was determined using quantitative real-time RT-PCR. Treatment with curcumin significantly increased TCF7L2 gene expression while treatment with LPS decreased TCF7L2 gene expression., When transfected into rat or mouse beta cells, is involved in maintaining expression of beta-cell genes regulating secretory function., No association with TCF7L2 variations and adiposity, but bias may have occurred by the evaluation of obesity in separate groups of glycaemic cases and controls, Carbohydrate quality and quantity modified risk of T2D associated with TCF7L2, which suggests that changes in risk attributable to the TCF7L2 variant are magnified under conditions of increased insulin demand, The genetic association of TCF-4 with ileal Ctohn's disease provides evidence that the decrease in Paneth cell alpha-defensins is a primary factor in disease pathogenesis., This meta-analysis demonstrates that four variants of TCF7L2 gene are all associated with type 2 diabetes mellitus, and indicates a multiplicative genetic model for all the four polymorphisms [review], No significant difference in overall amount or splicing pattern is observed between carriers and non-carriers of the type 2 diabetes risk allele., AP-1 and TCF-4 binding sites are the main regulatory regions directing versican production provide new insights into versican promoter regulation during melanoma progression., TCF7L2 is not a risk factor for obesity in Tunisians, but its effect on type II diabetes risk is modulated by obesity. The TCF7L2 rs7903146 T allele is associated with T2D susceptibility in nonobese individuals from Tunisia., Elevated hepatic glucose production and reduced insulinotropic effect of incretin hormones contribute to an increased risk of type 2 diabetes in carriers of the rs7903146 risk T allele of TCF7L2, Evidence of association with two independent TCF7L2 loci in a PCOS and glucose intolerant cohort., In the Tunisian population, TCF7L2-rs7903146 T allele confers an increased risk of developing type 2 diabetes, Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GLP-1R and GIP-R., Study provides the first evidence for the involvement of MAD2B in TCF4-mediated epithelial-mesenchymal transdifferentiation., The TCF7L2 rs7903146 polymorphism is not associated with the change in insulin secretion during GH treatment in short SGA children., Single nucleotide polymorphisms are strongly associated with the risk of type 2 diabetes in an East Asian population., The risk allele at TCF7L2 rs7903146 may have a role in the pathogenesis of premature adrenarche in lean subjects., epistatic effects of five candidate genes, including ADIPOQ, ENPP1, GHSR, PPAR and TCF7L2, are significantly associated with the risk of DN amongst Taiwanese T2D individuals., role for type 2 diabetes (T2D) risk-conferring gene TCF7L2 in insulin resistance in both Taiwanese and Caucasian youth., Frequency of the TT genotype of TCF7L2 polymorphsim is greater in latent autoimmune diabetic adults compared with normal controls., Daxx functions as a positive coregulator in modulating the beta-catenin/TCF4-dependent transcriptional potential via TCF4 interaction., No significant associations were seen between tcfl2 polymorphism and insulin sensitivity, In cystic fibrosis patients not treated with systemic glucocorticoids, the effect of TCF7L2 single nucleotide polymophrism is even greater in predicting risk of type 2 diabetes., Alternative splicing of TCF7L2 is Tissue-specific., We found no evidence for an association between TCF7L2 genotype and fetal and early postnatal growth. Furthermore, this TCF7L2 polymorphism was not associated with an increased risk of small-for-gestational-age, Data show that predicted risks were below average for carriers of the TCF7L2 CC genotype and above average for the CT and TT genotypes., This study concluded TCF7L2, a risk factor for type 2 diabetes in the general population, is also a risk factor for type 2 diabetes in African-American patients with SCZ or schizoaffective disorder., Beta-catenin and TCF4 activate the human StarD7 gene interacting with its promoter region through Wnt/beta-catenin signalling., our data show that the TCF7L2 rs7903146 polymorphism, a known risk factor for type 2 diabetes in the general population, also associates with NODAT, Single nucleotide polymorpisms, in TCF7L2 hanve no association with polycystic ovary syndrome or related clinical features in Chinese Women., TCF7L2 variant is not associated with risk of breast or ovarian cancer., alternatively spliced TCF7L2 may have different functional roles in omental and subcutaneous adipose tissue but is not associated with SNPs rs7903146 and rs12255372 or T2D status, Genetic variants in exon 4 of TCF7l2 were associated with impaired insulin secretion and incident diabetes and variants near 3' end were associated with insulin resistance in a Chinese cohort., Subjects with the unfavorable TT genotype of TCF7L2 showed higher values of fasting glucose and lower homeostasis model assessment of beta cell function at baseline., The rs7903146 variant of TCF7L2 significantly increased type 2 diabetes mellitus risk in the Palestinian population., These findings suggest that some splicing forms of TCF7L2 may be functionally important for regulation of MYC expression in colon tissue but this regulation is not directly dependent on rs6983267., rs7903146 T allele of TCF7L2 is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events, analysis of control of TCF-4 expression by VDR and vitamin D in the mouse mammary gland and colorectal cancer cell lines, TCF7L2 genotype does not significantly affect overall insulin sensitivity., Enhanced expression of TCF4 is associated with ulcerative colitis-associated neoplasia., diabetes-associated alleles of TCF7L2 are associated with less weight loss in response to lifestyle intervention, Individuals who are homozygous for the TCF7L2 rs7903146 T-risk allele are more senstive to low fat than to high fat weight-loss diets., Significant correlation between expression of a unique splicing form of TCF7L2 suggests that transcripts may share neuroendocrine functions important for brain, gut and pancreatic islets., There was no association of the genetic polymorhism rs7903146 of TCF7L2 with the occurrence of polycystic ovary syndrome in the Chinese population., Chinese patients with the C allele of TCF7L2rs290487(C/T) had higher total cholesterol levels and lower body mass index and heightened risk of developing type 2 diabetes mellitus., RT-PCR analysis of TCF7L2 mRNA levels in tumor samples revealed significantly lower levels in patients with metastasis when compared with those without metastasis., Intronic TCF7L2 variants may regulate alternative transcript isoforms, which in turn may have distinct physiologic roles., Reduced paracrine glucagon stimulation may contribute to the impairment of beta-cell function in the carriers TCF7L2 T-allele associated with increased risk of type 2 diabetes., rs7903146, a TCF7L2 intronic variant strongly associated with type 2 diabetes, is located in islet-selective open chromatin., Axin downregulates TCF-4 transcription via beta-catenin and independently of p53., The TCF7L2 rs7903146 T allele was inversely associated with prostate cancer using a dominant genetic model, Studies identified significant association between variants in CDKN2A/B, CDKAL1 and TCF7L2, and type 2 diabetes in a Han Chinese cohort, indicating these genes as strong candidates conferring susceptibility to type 2 diabetes across different ethnicities., The T-allele of TCF7L2 rs7903146 polymorphism was independently associated with increasing fasting glucose values toward hyperglycemia in the follow-up., beta-catenin/TCF4 transactivates miR-30e during intestinal cell differentiation., A minimal promoter for intestinal cell kinase contains functional sites for beta-catenin/TCF7L2 and FOXA., Variants located within the gene TCF7L2 are strongly associated with Type-2 diabetes but not with Metabolic Syndrome., TCF7L2 variant affects risk for diabetes by modification of the insulinotropic effect of the incretin hormones may be true, but, the impaired incretin effect might simply be secondary to impaired glucose intolerance., No difference in nuclear beta-catenin signal intensity was found, which may be caused by an alteration in Wnt pathway in microsatellite stable sporadic tumors by unknown mechanisms leading to lower TCF-3, 4 protein expression., rs7903146 C/T polymorphism associated with gestational diabetes in Greek women, TCF7L2 common genetic variants of susceptibility are associated only with low GADA antibody titre in LADA patients., Our study replicates the association between rs7903146 and IFG risk in a population-based, longitudinal cohort of Caucasians but not in African Americans., Findings suggest that TCF7L2 is a central node in the regulation of human diabetes and other disease-associated genes., TT genotype of rs12255372 and rs7903146 TCF7L2 gene variants is associated with lower insulin secretion and higher cardiosympathetic activity., these data reveal a lithium-induced RNA switch favoring the expression of TCF7L2-short forms, which results in a transcriptional de-repression of lithium target genes negatively regulated by TCF7L2-long forms., Maternal TCF7L2 variants are associated with glucose levels carry an increased risk of adverse pregnancy outcome in women without overt diabetes., Genome-wide analysis of DNA cis-regulatory regions bound by the intestine-restricted factor CDX2 in colonic cells uncovered highly significant overrepresentation of sequences that bind TCF4, a transcriptional effector of intestinal Wnt signaling., Data show that NGX6 could suppress the translocation of beta-catenin from nucleus and cytoplasm to plasma membrane, inhibit the activity of TCF4 transcript factor, and down-regulate the expression of Wnt-direct-targeted genes., p15RS inhibits Wnt signaling by interrupting beta-catenin.TCF4 complex formation and that Wnt signaling initiates downstream gene expression by removing p15RS from promoters., rs12255372 and rs13266634 markers are independent genetic type 2 diabetes risk factors in a Russian population., It has become clear that TCF7L2 plays an important role for several vital functions in the pancreatic islet. In pancreatic islets four splice variants of TCF7L2 are predominantly expressed., Middle-aged normoglycaemic individuals carrying the rs7903146 TCF7L2 risk TT genotype show early signs of dysregulated glucose metabolism, decreased processing of proinsulin and elevated GIP secretion following a meal challenge., In African Americans, these observations suggest that rs7903146 is the trait-defining polymorphism of TCF7L2 associated with type 2 diabetes risk., TCF7L2 variation is associated with an increased risk of early-onset type 2 diabetes among AA youth, and the association appears to be stronger in AA than NHW youth., SNP in the TCF7L2 gene are associated with differences in insulin secretion, blood pressure, blood lipids and coagulation in MetS patients, and may be modulated by saturated fatty acids in plasma or insulin resistance., strong associations of two SNPs (rs7903146 and rs12255372) in TCF7L2 with FPG and HbA1c levels, TCF7L2 diabetes risk variants, either as single-nucleotide polymorphisms or as haplotypes, detrimentally influence beta-cell function, Data suggest that conserved splicing motifs may have a major influence on the transcriptional activity and functional properties of TCF-4 isoforms and alter the characteristics of the malignant phenotype., HIPK2-dependent phosphorylation caused the dissociation of LEF1, TCF4, and TCF3 from a target promoter in vivo., role of beta-catenin/Tcf4/survivin signaling in determining the fate of human corneal epithelial stem cells in different media, Genetic variations in transcription factor 7-like 2 gene is associated with breast cancer., function-specific transcripts of TCF7L2, which possessed distinct physiological and pathophysiological effects on the beta-cell. The presence of deleterious TCF7L2 splice variants may be a mechanism of beta-cell failure in T2DM., T-cell factor 4 functions as a tumor suppressor whose disruption modulates colon cell proliferation and tumorigenesis., Type 2 diabetic carriers of the TCF7L2 risk alleles in rs1225537 and rs7901346 had increased risk of type 2 diabetes and elevated HbA(1c), Activation of the MAPK pathway by FGFR-3 is also required for the induction of Paneth cell markers in addition to and independent of the effect of FGFR-3 on TCF4/beta-catenin activity, The association reported here with a well-known diabetes variant suggests that the observed comorbidity is partially caused by genetic risk variants., These results suggest that TCF7L2 variants rs7903146 rs12255372, and rs11196205 are significantly associated with angiographically diagnosed coronary artery disease, specifically in patients with type 2 diabetes., The study suggests a connection between CD133 and EGR1 and emphasizes the importance of the EGR1/TCF4/CD133/LGR5 network in colorectal cancer., ZIPK may serve as a transcriptional regulator of canonical Wnt/beta-catenin signaling through interaction with NLK/TCF4., The highest risk of T2DM was 3.1, obtained by the genotype combination of the three associated SNPs, TCF7L2 rs7903146 polymorphism influences MetS risk, which is augmented by both gender and dietary dietary saturated fat intake., Several studies have shown that decreased TCF7L2 protein inhibits the insulin secretory response to oral glucose through impaired incretin action(GLP-1, GIP)., Melanoma cell phenotype switching behaviour is regulated by differential LEF1/TCF4 activity., High TCF4 is associated with glioma progression., Results confirm association of rs7903146 in the TCF7L2 gene with increased risk of type 2 diabetes. The T allele is strongly associated with nephropathy, especially in early onset of diabetes.d, Tcf7l2 plays a role in regulating glucose tolerance, suggesting that overexpression of this gene is associated with increased risk of T2D., These results support the recent findings that rs7903146 of TCF7L2 gene is an important genetic risk factor for the development of type 2 diabetes in multiple ethnic groups., TCF7L2 allelic variations are associated with gastric function, satiation, and GLP-1 levels, Tcf-4 binds to the potential binding sites in the gene promoter of AKT1., Capsaicin treatment suppressed TCF-4 expression and disrupted the interaction of TCF-4 and beta-catenin in human colorectal cancer cells., Results suggest that Tcf-4 can act as a repressor or activator of breast cancer progression by regulating OPN (osteopontin) expression in a Wnt-dependent manner., TCF7L2 polymorphism was associated with higher fasting proinsulin at baseline, higher baseline proinsulin, Brief Report, evaluation of TCF7L2 polymorphisms in posttransplant diabetes mellitus(PTDM)in kidney transplant patients treated with tacrolimus;in late-onset PTDM, frequency of rs7903146 TT genotype and T minor allele were significantly increased compared to controls, We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown., A novel polyadenylation signal within TCF7L2 identified that can result in the production of isoforms that act to repress TCF/LEF-dependent target genes., The odds ratios for stroke/TIA were...0.99 (95%CI 0.78-1.25) for rs7903146/TCF7L2. Further exploration revealed that male patients with the T allele of rs7903146/TCF7L2 had a worse clinical outcome compared with male patients carrying the C allele., we provide new insight into how TCF4L2 affects miRNA expression, and how these changes in miRNA expression may influence cancer progression., results indicate a novel mechanism through which the Wnt transcription factor TCF4 mediates chemoradioresistance. Moreover, they suggest that TCF4 is a promising molecular target to sensitize resistant tumor cells to (chemo-) radiotherapy, Tumor-suppressive effects of psoriasin (S100A7) are mediated through the beta-catenin/T cell factor 4 protein pathway in estrogen receptor-positive breast cancer cells., FasL (TCF/LEF1) binding elements formed complexes with the TCF-4 and beta-catenin transcription factors in vitro and in vivo., An SNP in TCF7L2 (rs7903146) is associated with autoimmune diabetes and type 2 diabetes in European dataset and Hungarian dataset; this SNP was not associated with type 1 diabetes. [META-ANALYSIS; CASE-CONTROL STUDY], Data show that beta-catenin/BCL9-Like (BCL9L)/T-cell factor 4 (TCF4) signalling directly targets the GCM1/syncytin pathway and thereby regulates the fusion of human choriocarcinoma cells., Genotype of the TCF7L2 rs12255372 gene was associated with lower fasting plasma glucose (p = 0.001) and lower homeostasis model assessment of insulin resistance (HOMA-R; p = 0.001) in nonobese children, Knockdown of either beta-catenin or TCF-4 induced LTR activity in astrocytes., Sox4 may serve as a positive regulator of beta-catenin signaling through alteration in TCF4 expression during morular differentiation of endometrial carcinoma cells, leading to inhibition of cell proliferation., These findings demonstrate that transcription factor TCF4 plays an important role in determining or maintaining the phenotype and functional properties of human corneal epithelial stem cells., TCF7L2 may be an important susceptibility gene for type 2 diabetes mellitus in some Chinese populations, Single nucleotide polymorphism in TCF7L2 is associated with schizophrenia., SPINDLIN1, which may be a novel substrate of the Aurora-A kinase, promotes cancer cell growth through WNT/TCF-4 signaling activation., Analyses indicate that T2D genetic risk is primarily mediated through the effect of TCF7L2 in African Americans., genetic association studies in a population in China, Genetic variants associated with the reproductive phenotype have been mapped to the fibrillin-3 (FBN3) gene and to a novel transcription factor-7-like 2 (TCF7L2) locus (rs11196236 G)., MUC1-C oncoprotein contributes to TCF7L2 activation and thereby promotes cyclin D1 expression in breast cancer cells., Dietary fiber intake modulates the association between variants in TCF7L2 and weight loss during a lifestyle intervention., rs4132670 is a non-tissue-specific candidate functional single nucleotide polymorphism that has the potential to play a role in TCF7L2 gene expression and type 2 diabetes risk., genetic association studies in population in Latvia, None of the 12 SNPs in the six genes (KCNJ11, TCF7L2, SLC30A8, HHEX, FTO and CDKAL1) uncovered in the genome-wide association studies were associated with polycystic ovary syndrome., Report association of TCF7L2 haplotypes with type 2 diabetes and gestational diabetes., The associations between SNPs of TCF7L2, CDKAL1, SLC30A8 and HHEX and the development of DR and DN., TCF7L2rs12255372 variant (T/T) is associated with increased risk of gestational diabetes mellitus in Caucasian women., TCF7L2 HapA attenuates the positive association between animal protein intake and long-term body weight change in middle-aged Europeans but does not interact with the GI of the diet., The type 2 diabetes susceptible genotype of TCF7L2 was associated with a lower risk of islet autoantibodies and progression to type 1 diabetes., TCF7L2 and ADIPOQ together might play an important role in explaining these traits and to understand the biological and genetic mechanisms underlying T2D, and the role of other T2D genes must also be evaluated with these continuous traits, The TCF7L2 rs7903146 and FTO rs8050136 polymorphisms, and particularly a weighted risk score of T2 diabetes risk alleles, predict diabetes after gestational diabetes mellitus., TCF-4, beta-catenin, and SMAR1 tether at the -143-nucleotide site on the HIV LTR to inhibit HIV promoter activity., Kindlin 2 forms a tripartite complex with beta-catenin and TCF4., Older cardiovascular disease patients with the TCF7L2 TT genotype performed worse on tests of attention/executive/ psychomotor speed than CC and CT genotype carriers., Both Sox9 and KLF4 interact with beta-catenin in an immunoprecipitation assay and reduce its binding to TCF4., The specific TCF-4J isoform, which lacks a regulatory SxxSS motif, has robust tumor-initiating potential under hypoxic conditions., Dietary fibre intake may modify the association between TCF7L2 rs7903146 and incidence of type 2 diabetes. Higher fibre intake may associate with protection from type 2 diabetes only among non-risk allele carriers., A correlation was observed between D-glucuronyl C5-epimerase (GLCE), TCF4 and beta-catenin expression in breast cancer cells and primary tumors, suggesting an important role for TCF4/beta-catenin in regulating GLCE expression both in vitro and in vivo., In addition to the involvement of TCF7L2 in Type 2 diabetes mellitus, TCF7L2 genetic variability also contributes to the development of diabetic complications such as retinopathy and cardiovascular autonomic neuropathy., Findings suggest that the effect of TCF7L2 on diabetes risk may include reduced secretion of GIP (glucose-dependent insulinotropic polypeptide)., The distribution of CC, CT and TT genotypes of SNP rs7903146 of the TCF7L2 gene was not different between patients and controls, and no association between the genotype and indicators of disease severity or smoking history was found, TCF7L2 rs7903146 impairs islet function and morphology in non-diabetic individuals., Healthy young males and elderly persons who are carriers of the mutant allele for rs7903146 have an impaired postprandial lipid metabolism that may be mediated by an alteration in adipokine regulation, and may be related to the higher cardiovascular risk., rs7754840 (CDKAL1) was associated in the nonobese type 2 diabetic subgroup, and for rs7903146 (TCF7L2), association was observed for early-onset type 2 diabetes., Single nucleotide polymorphisms rs7895340 and rs11196205 of TCF7L2 showed a significant association with type 2 diabetes mellitus in Thai patients., Study demonstrates that TCF7L2 overexpression fosters beta cell regeneration. Findings imply correlation of TCF7L2 levels and new beta cell formation., TCF7L2 binds GATA3 and represses transcription at a subset of sites in MCF7 cells., Data suggest that TCF7L2 and Wnt signaling are negative regulators of gluconeogenesis in hepatocytes; TCF7L2 is among the downstream effectors of insulin in hepatocytes; insulin stimulates TCF7L2 expression in hepatocytes., the rs7903146 T allele was associated with an increased risk for T2DM, but the rs290487 C allele is not associated with T2DM in the Chinese Han population., investigation of involvement of an SNP TCF7L2 (rs7903146; previously identified in genome-wide association studies), cis-regulatory elements, and chromatin assembly and disassembly in genetic/epigenetic predisposition to type 2 diabetes, The absence of any difference between genotype frequencies among study groups indicates that no association persists with TCF7L2 gene rs7903146 polymorphism and type 2 diabetes mellitus., Tcf-4 knockdown shows better efficacy for inhibiting proliferation and inducing apoptosis of colorectal cancer cells, which may be related to increased FOXO4 transcriptional activity, TCF4 was significantly overexpressed in hepatocellular carcinoma., Individuals with the TCF7L2 rs12255372 risk genotype may reduce body adiposity by consuming a diet lower in total fat., Donor TCF7L2 rs290487 polymorphism is associated with an increased risk of new-onset diabetes mellitus (NODM) after liver transplantation and has a potential clinical value for the prediction of NODM., Data indicate no association was found between the IVS4G>T mutation in the TCF7L2 gene and diabetes., there is a significant association between the TCF7L2 gene and risk of breast cancer regardless of ethnicity and/or Native American ancestry., Data suggest that TCF7L2 splicing in abdominal adipose tissue is regulated by weight loss and is associated with obesity, hyperglycemia, and high levels of serum free fatty acids., genome-wide association study in an Arab population in Lebanon, The strong contribution of TCF7L2 gene variants to type 2 diabetes among Tunisians, In African Americans, seven of the 29 SNPs examined were found to be associated with T2D risk at P = 0.05, including rs7903146 (TCF7L2)., increase in the risk of type 2 diabetes with rs7903146, rs12255372, rs11196205, rs7901695, rs7895340 and rs4506565 but not with rs11196218 or rs290487 single-nucleotide polymorphisms, Data suggest that an SNP in TCF7L2 (rs7903146) is associated with type 2 diabetes in African Americans. [META-ANALYSIS; Genome-Wide Association Studies], Nuclear TCF4 correlate with cerebral metastasis of lung adenocarcinomas., We found that the T allele of the SNP rs7903146 of TCF7L2 was significantly associated with type 2 diabetes risk (odds ratio of 3.92 for genotype TT in the recessive genetic model, p = 0.004 and 1.5 for T allele, p = 0.032)., Activation of TCF4 is associated with glioblastoma multiforme., SOX9 regulates low density lipoprotein receptor-related protein 6 (LRP6) and T-cell factor 4 (TCF4) expression and Wnt/beta-catenin activation in breast cancer., TCF7L2 single nucleotide polymorphisms are associated with increased susceptibility to type 2 diabetes mellitus., Data indicate associations of SNPs in eight loci CXCR4, HHEX, FOXA2, NGN3, TCF7L2, FLJ39370 (C4orf32), LOC646279 (RPL21P7) and THADA with body mass index (BMI) and weight., the LRP6(R611C) mutation diminishes TCF7L2-dependent transcription of the IR while it increases the stability of IGFR and enhances mTORC1 activity., TCF7L2-rs7903146 is associated with diabetic nephropathy in Caucasian type 2 diabetes and suggest that TCF7L2 promotes pathological retinal neovascularization via ER stress-dependent upregulation of VEGFA., The transcriptional activity of the ABCD2 promoter was strongly increased by ectopic expression of beta-catenin and TCF-4., ZNRF3 inhibits gastric cancer cell growth and promotes cell apoptosis by affecting the Wnt/beta-catenin/TCF4 signalling pathway., The rs7903146C/T polymorphism of the TCF7L2 gene had a significant effect on type 2 diabetes risk in a Chinese Han population., the genotypes of rs7903146 (IVS3C/T) in TCF7L2 have no major impact on T2DM; the CC genotype and the recessive model of rs290487 (IVS3C/T) and the haplotype CC of rs7903146 (IVS3C/T) and rs290487 (IVS3C/T) in TCF7L2 gene are associated with T2DM., TCF7L2 polymorphisms were associated with HD and maybe cancer risk as well., strong association of the TCF7L2 SNPs with type 2 diabetes mellitus, by pooling all available qualified data from genetic studies on rs12255372 and T2DM, we have confirmed that rs12255372 is significantly associated with susceptibility to T2DM in the global population., Increased TCF4 expression may contribute to cartilage degeneration in osteoarthritis by augmenting NF-kappaB signaling., acetylation of TCF4E is a novel regulatory mechanism that diversifies the transcriptional output of Wnt/beta-catenin signaling, results suggest synergistic effects of WNT16a insertion and the at-risk 'T' allele of TCF7L2 (rs7903146) for elevating the expression of TCF7L2 in human pancreas which may affect the regulation of downstream target genes involved in the development of T2D, The TCF-4C isoform lacking exon 4 is associated with a malignant phenotype compared with the exon 4-harbouring TCF-4D isoform, indicating that exon 4 of TCF-4 plays a prominent role in hepatocellular carcinoma development., The consequence of TCF-4J isoform expression was upregulation of genes associated with tripartite Wnt/beta-catenin, insulin/IGF-1/IRS1 and Notch signal transduction pathway activation, which contribute to the pathogenesis of hepatocellular carcinoma., SNPs in TCF7L2 was replicated in this study (P = 0.004; combined analysis P = 3.8 x 10(-6)), and type 2 diabetes SNPs at or near CDKAL1, CDKN2A/B, and IGF2BP2 were associated with CFRD, GRG5/AES interacts with TCF4 and represses Wnt-mediated transcription both in human cells and zebrafish embryos., Data indicate that henryin impaired the association of beta-catenin/TCF4 transcriptional complex likely through directly blocking the binding of beta-catenin to TCF4., The meta-analysis suggests that TCF7L2 rs7903146 genetic polymorphism was associated with increased risk of gestational diabetes mellitus., compared with the control group. CONCLUSION, TCF7L2 variants are probably not implicated in polycystic ovary syndrome development in South Brazilian women, this study investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet., Significant associations have been found between the TCF7L2 rs7903146 polymorphisms and the risk for breast, prostate and colon cancers. (Meta-analysis), Marked expression of TCF7L2 in oligodendrocytes is restricted to a well defined time period during developmental myelination in human and mouse central nervous system tissue samples., we have found no association between TCF7L2 and type 2 diabetes in Chinese population, The TCF7L2 (T) allele was increased in the type 2 diabetes group (0.36) compared to the controls, Data indicate transcription factor TCF7L2 as a regulator of KIBRA gene expression., results suggest that hydrochlorothiazide (HCTZ)-associated new onset diabetes; observations suggest that an environmental risk factor such as HCTZ treatment further increases diabetes risk in TCF7L2 risk allele carriers, There is weak or no contribution of TCF7L2 gene polymorphism to polycystic ovary syndrome in Tunisian women., Carriers of TCF7L2 rs7903146 exhibited a non-significant increase of plasma sphingomyelins., Positive significant association between impairment in wound healing of diabetic foot ulcers and the TT genotype of rs7903146 (C/T) variant of TCF7L2 gene was found in a north Indian population., A meta-analysis suggests that the TCF7L2 rs12255372 T allele is a low-penetrant risk factor for breast carcinogenesis., Investigation of the genetic factors underlying bipolar disorder, results show strong evidence of a SNP-body mass index interaction involving a variant in TCF7L2 at the genome-wide level, Association of rs7014346 in POU5F1P1, rs989902 in PTPN13, and rs7003146 in TCF7L2 with variations in the risk of breast cancer in a Chinese Han population., Alternative human liver transcripts of TCF7L2 bind to the gluconeogenesis regulator HNF4alpha at the protein level., TCF7L2 rs7903146 Polymorphism is associated with Diabetes Mellitus, Type 2., the rs12255372 SNP shows a weaker association with type 2 diabetes compared with rs7903146, Transcription factor 7-like 2 gene polymorphism rs7903146 is associated with stroke in type 2 diabetes., We described for the first time a strong relationship between the TCF7L2 gene variant rs7903146 and cardiovascular disease in end-stage renal disease patients., Data suggest up-regulation of TCF4 (T cell transcription factor 4) expression and Wnt signaling play roles in placentation; induction/nuclear recruitment of TCF4 and coactivator beta-catenin are exhibited in conditions promoting trophoblast motility., TCF7L2 genetic polymorphisms may contribute to susceptibility to polycystic ovary syndrome, especially for the rs7903146 C-->T polymorphism among Caucasians and Asians, genetic association studies in population of pregnant women in Mexico, Our results point to a protein complex binding across rs7903146 within TCF7L2 and suggests a possible mechanism by which this locus confers its T2D risk., The findings of this systemic analysis suggest that the polymorphism of TCF7L2 rs7903146 may not be associated with the susceptibility to polycystic ovary syndrome., This study found no association between rs7903146 polymorphism in the TCF7L2 gene and the increased risk for development of CKD caused by primary glomerulopathy and analysed tubulointerstitial nephropathy., Methylation in TCF7L2 promoter is further correlated with fasting glucose in peripheral blood DNA, which sheds new light on the role of epigenetic regulation of TCF7L2 in type 2 diabetes., Data suggest that the ranscription factor 7-like 2 variant rs7903146 (TCF7L2 rs7903146) to the pathogenesis of type 2 diabetes can still be seen as a mechanism impairing insulin secretion., Among hyperglycemic men, a risk allele in TCF7L2 may increase the risk of prostate cancer., study suggests that CREPT acts as an activator to promote transcriptional activity of the beta-catenin.TCF4 complex in response to Wnt signaling., SOX10 facilitates TCF4 to bind to beta-catenin and form a stable SOX10/TCF4/beta-catenin complex and trans-activate its downstream target gene in human hepatocellular carcinoma, Tcf7l2 is regulating proinsulin expression directly via Isl1, Ins1 and indirectly via MafA, NeuroD1 and Pdx1., LHX4 facilitate TCF4 to bind to beta-catenin and form a stable LHX4/TCF4/beta-catenin complex and transactive its downstream target gene, TCF7L2 rs4506565 variant (T/T) is associated with increased risk of gestational diabetes mellitus (GDM) and plasma resistin concentrations in women with GDM., in human immortalized lymphocytes carrying the at-risk T/T genotype, first the differential expression of TCF7L2 splice variants implies a regulation, at least for exon 4, by TRA2B, We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 x 10(-94), there is no risk of diabetic retinopathy among individuals with the TCF7L2 polymorphisms rs7903146., The intestine-specific transcription factor CDX2 and Wnt effector TCF7L2 bind near rs16969681, with significantly higher affinity for the colorectal cancer risk allele., The T-allele of rs12255372, rs7903146, and rs290487 polymorphisms of TCF7L2 confer susceptibility to T2DM in the Kurdish population of Iran, TCF7 L2 gene variation affected the decrease of fasting blood glucose after gastric bypass in obese patients with type 2 diabetes, independently of weight loss., This study suggests that the SNP rs1800592 in the UCP1 gene is associated with increased risk of PDR in the Chinese type 2 diabetes mellitus population., data suggest that the TCF7L2 SNPs rs7903146 and rs12255372 may not significantly contribute to T2D susceptibility in this population, The TCF7L2 rs7903146 TT/TC genotype was associated with lower levels of total cholesterol, low-density lipoprotein, and high-density lipoprotein in hepatitis C genotype3 HIV coinfected patients., Tcf7l2 may play key role in glucose metabolism through actions beyond pancreatic beta cells., The results support a central role of CDKAL1 and TCF7L2 in T2DM susceptibility in Southwest Asian populations and provide a plausible component for understanding molecular mechanisms involved in the disease., The T allele of the TCF7L2 rs7903146 SNP is associated with a significantly higher risk of type 2 diebtes in an Algerian population., there is a putative genetic connection between TCF7L2 and EXT in the context of Hereditary Multiple Exostoses, results confirm the association between the TCF7L2 rs7903146 polymorphism and increase risk for type 2 diabetes in Southern-Brazil., There were no significant associations between polycystic ovary syndrome and TCF7L2 rs7903146 or rs12255372 polymorphisms--{REVIEW}, Our results support a genetic interaction in the TCF7L2 SNPs as a predictor of disease recurrence after curative RP in localized prostate cancer patients., no association of single nucleotide polymorphisms and type 2 diabetes mellitus susceptibility in Chinese population, Studies indicate that TCF7L2 transcription factor gene polymorphisms were significantly associated with an increased risk of breast cancer., The T-Allele of the TCF7L2 rs7903146 is a significantly risk factor for impaired proinsulin conversion. [Meta-analysis], TCF7L2 gene polymorphism of geriatric patients with coronary heart disease contributes to development of a metabolic syndrome and reduces term of their life., In subjects at risk for T2 Diabetes mellitus the TCF7L2 polymorphisms were associated with reduced Rate of appearance of exogenous glucose into systemic circulation, causing reduced postprandial blood glucose increase and lower insulin secretion rate., The rs12255372 SNP of TCF7L2 and D76N of PDX-1 genes may confer susceptibility to T2DM in the population living in Mashhad, Iran., The T-allele frequencies of TCF7L2 polymorphisms rs12255372 and rs7903146 were 30% (26-35%), 32% (27-37%) and 29% (25-34%), 36% (31-41%), respectively., there is no significant association between the rs11196218A/G polymorphism and the risk of type 2 diabetes mellitus in the Chinese Han population., TCF7L2 rs10885409 C allele is a T2DM risk factor in Emiratis; this association is modulated by obesity status, but the Pro12Ala mutation in PPAR-gamma2 is not associated with T2DM risk in this population, provides substantial evidence that the rs7903146 variant is significantly associated with the risk of diabetic retinopathy in Caucasian populations, the TCF7L2 rs12255372 (G>T) polymorphism might be one of the most important genetic factors associated with T2DM susceptibility., rs12255372 and rs4506565 variants(but not rs7903146) of TCF7L2 show an association with type 2 diabetes mellitus for the Saudi population of the Eastern Province of Saudi Arabia, The data suggested that the genetic polymorphisms of the TCF7L2 gene were associated with T2DM in the Uygur population of China., A genetic variant harbored within the TCF7L2 locus rs7903146 impairs glucose tolerance through effects on glucagon as well as on insulin secretion., Transcription factor 7-like 2 (TCF7L2) gene encodes the TCF-4 transcription factor, which forms a part of the Wnt signaling pathway., Our meta-analysis indicated the association between TCF7L2 rs7903146 polymorphism and low plasma triglyceride (TG) level in subjects with type 2 diabetes., this study demonstrates the presence of the rs7903146 polymorphism in the Iranian population, suggesting susceptibility to type 2 diabetes, Data indicate that triglycerides were significantly associated with the T risk allele of the transcription factor 7-like 2 (TCF7L2) gene., Meta-analysis revealed that the T allele of rs7903146 was also correlated with T2DM susceptibility., Despite limited sample size, the study indicates that rs7903146-T allele in TCF7L2 was associated with higher mean nocturnal glucose dependent on body composition, which might suggest that rs7902146 affects liver-specific aspects of glucose metabolism., polymorphism may contribute to the risk of diabetic nephropathy, Risk alleles for 6 loci increased glucose levels from birth to 5 years of age (ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2, The T allele of TCF7L2 rs7903146 polymorphism was associated with susceptibility of gestational diabetes mellitus in overall population in white, Hispanic/Latino and Asian sub-groups. Meta-analysis.,
OMIM_DISEASE Diabetes mellitus, type 2, susceptibility to,
SP_COMMENT developmental stage:Highly expressed in crypt regions and barely detectable in villi in epithelium from fetal small intestine at week 16. At week 22 expression in villi had increased strongly., disease:Constitutive activation and subsequent transactivation of target genes may lead to the maintenance of stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal differentiation and constitute the primary transforming event in colorectal cancer (CRC)., disease:Genetic variations in TCF7L2 are associated with susceptibility to noninsulin-dependent diabetes mellitus (NIDDM) [MIM:125853]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance., domain:The promoter-specific activation domain interacts with the transcriptional coactivator EP300., function:Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine., PTM:Polysumoylated. Sumoylation is enhanced by PIAS family members and desumoylated by AXAM/SENP2. Sumoylation/desumoylation regulates TCF4 transcription activity in the Wnt signaling pathway without altering interaction with CTNNB1 nor binding DNA., similarity:Belongs to the TCF/LEF family., similarity:Contains 1 HMG box DNA-binding domain., subcellular location:Diffuse pattern. Colocalizes with SUMO1 and PIAS4 in a subset of PML (promyelocytic leukemia) nuclear bodies., subunit:Interacts with TGFB1I1 (By similarity). Interacts with CTNNB1 (via the armadillo repeat); forms stable transcription complex. Interacts with EP300. Interacts with NLK., tissue specificity:Detected in epithelium from small intestine, with the highest expression at the top of the crypts and a gradient of expression from crypt to villus. Detected in colon epithelium and colon cancer, and in epithelium from mammary gland and carcinomas derived therefrom.,