View source for TCF7L2

{{Infobox_gene}}
'''Transcription factor 7-like 2 (T-cell specific, HMG-box)'''  also known as '''TCF7L2''' or '''TCF4''' is a [[protein]] acting as a [[transcription factor]] that in humans, is encoded by the ''TCF7L2'' [[gene]].<ref name="entrez_ 6934">{{cite web | title = Entrez Gene: TCF7L2  | url =https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6934 }}</ref><ref name="pmid1741298">{{cite journal | vauthors = Castrop J, van Norren K, Clevers H | title = A gene family of HMG-box transcription factors with homology to TCF-1 | journal = Nucleic Acids Research | volume = 20 | issue = 3 | pages = 611 | date = February 1992 | pmid = 1741298 | pmc = 310434 | doi = 10.1093/nar/20.3.611 }}</ref> The TCF7L2 [[gene]] is located on chromosome 10q25.2-q25.3, contains 19 [[exon]]s, and has [[autosomal dominant]] inheritance.<ref name="entrez_gene">{{cite web|url=https://www.ncbi.nlm.nih.gov/gene/6934|title=TCF7L2 transcription factor 7 like 2 [Homo sapiens (human)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2017-11-30}}</ref><ref name="OMIM">{{OMIM|602228|TRANSCRIPTION FACTOR 7-LIKE 2;TCF7L2 }}{</ref> The TCF7L2 gene is [[Polymorphism (biology)|polymorphic]] and [[Pleiotropy|pleiotropic]].<ref name="Zhu_2017">{{cite journal | vauthors = Zhu L, Xie Z, Lu J, Hao Q, Kang M, Chen S, Tang W, Ding H, Chen Y, Liu C, Wu H | title = TCF7L2 rs290481 T>C polymorphism is associated with an increased risk of type 2 diabetes mellitus and fasting plasma glucose level | journal = Oncotarget | volume = 8 | issue = 44 | pages = 77000–77008 | date = September 2017 | pmid = 29100364 | pmc = 5652758 | doi = 10.18632/oncotarget.20300 }}</ref> As a member of the [[TCF/LEF family|TCF family]], TCF7L2 can form a bipartite transcription factor and influence several biological pathways, including the [[Wnt signaling pathway|Wnt signalling pathway]].<ref name="Jin_2008"/> The [[Single-nucleotide polymorphism|single nucleotide polymorphism (SNP)]] within the TCF7L2 gene, rs7903146, is, to date, the most significant genetic marker<ref>{{cite journal | vauthors = Vaquero AR, Ferreira NE, Omae SV, Rodrigues MV, Teixeira SK, Krieger JE, Pereira AC | title = Using gene-network landscape to dissect genotype effects of TCF7L2 genetic variant on diabetes and cardiovascular risk | journal = Physiological Genomics | volume = 44 | issue = 19 | pages = 903–14 | date = October 2012 | pmid = 22872755 | doi = 10.1152/physiolgenomics.00030.2012 }}</ref> associated with [[Diabetes mellitus type 2|Type 2 diabetes mellitus (T2DM)]] risk. SNPs in this gene are especially known to be linked to higher risk to develop type 2 diabetes,<ref name="Jin_2008">{{cite journal | vauthors = Jin T, Liu L | title = The Wnt signaling pathway effector TCF7L2 and type 2 diabetes mellitus | journal = Molecular Endocrinology | volume = 22 | issue = 11 | pages = 2383–92 | date = November 2008 | pmid = 18599616 | doi = 10.1210/me.2008-0135 }}</ref> [[gestational diabetes]],<ref name="Zhang_2013" /> and multiple other diseases.<ref name="Torres_2017">{{cite journal | vauthors = Torres S, García-Palmero I, Marín-Vicente C, Bartolomé RA, Calviño E, Fernández-Aceñero MJ, Casal JI | title = Proteomic Characterization of Transcription and Splicing Factors Associated with a Metastatic Phenotype in Colorectal Cancer | journal = Journal of Proteome Research | date = November 2017 | pmid = 29131639 | doi = 10.1021/acs.jproteome.7b00548 | volume=17 | pages=252–264}}</ref><ref name="Liu_2017" /><ref name="Vallée_2017" />

[[Image:TCF7L2 beta-catenin BCL9.png|left|thumb|150px|Structure of complex between TCF7L2 (orange), [[beta-catenin|β-catenin]] (red), and [[BCL9]] (brown).<ref name="pmid17052462">{{PDB|2GL7}}; {{cite journal | vauthors = Sampietro J, Dahlberg CL, Cho US, Hinds TR, Kimelman D, Xu W | title = Crystal structure of a beta-catenin/BCL9/Tcf4 complex | journal = Molecular Cell | volume = 24 | issue = 2 | pages = 293–300 | date = October 2006 | pmid = 17052462 | doi = 10.1016/j.molcel.2006.09.001 }}</ref>]]

== Function ==

TCF7L2 is a transcription factor influencing the [[Transcription (genetics)|transcription]] of several [[genes]] thereby exerting a large variety of functions within the cell. It is a member of the TCF family that can form a bipartite transcription factor ([[Beta-catenin|β-catenin]]/[[TCF/LEF family|TCF]]) alongside β-catenin.<ref name="Jin_2008"/> Bipartite transcription factors can have large effects on the [[Wnt signaling pathway|Wnt signalling pathway]].<ref name="Jin_2008"/> Stimulation of the Wnt signaling pathway leads to the association of β-catenin with [[BCL9]], translocation to the nucleus, and association with TCF7L2,<ref name ="pmid16567498">{{cite journal | vauthors = Lee JM, Dedhar S, Kalluri R, Thompson EW | title = The epithelial-mesenchymal transition: new insights in signaling, development, and disease | journal = The Journal of Cell Biology | volume = 172 | issue = 7 | pages = 973–81 | date = March 2006 | pmid = 16567498 | pmc = 2063755 | doi = 10.1083/jcb.200601018 }}</ref> which in turn results in the activation of Wnt target genes. The activation of the Wnt target genes specifically represses proglucagon synthesis in enteroendocrine cells.<ref name="Jin_2008"/><ref name="OMIM" /> The repression of TCF7L2 using [[HBP1|HMG-box repressor (HBP1)]] inhibits Wnt signalling.<ref name="Jin_2008"/> Therefore, TCF7L2 is an effector in the Wnt signalling pathway. TCF7L2's role in glucose metabolism is expressed in many tissues such as gut, brain, liver, and skeletal muscle. However, TCF7L2 does not directly regulate [[glucose metabolism]] in [[Beta cell|β-cells]], but regulates glucose metabolism in pancreatic and liver tissues.<ref name="Facchinello_2017">{{cite journal | vauthors = Facchinello N, Tarifeño-Saldivia E, Grisan E, Schiavone M, Peron M, Mongera A, Ek O, Schmitner N, Meyer D, Peers B, Tiso N, Argenton F | title = Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 9605 | date = August 2017 | pmid = 28851992 | pmc = 5575064 | doi = 10.1038/s41598-017-09867-x | bibcode = 2017NatSR...7.9605F }}</ref>

The TCF7L2 gene encoding the TCF7L2 transcription factor, exhibits multiple functions through its polymorphisms and thus, is known as a pleiotropic gene. Type 2 diabetes T2DM susceptibility is exhibited in carriers of TCF7L2 rs7903146C>T<ref name="Chen_2018">{{cite journal | vauthors = Chen Y, Zhao Y, Li YB, Wang YJ, Zhang GZ | title = Detection of SNPs of T2DM susceptibility genes by a ligase detection reaction-fluorescent nanosphere technique | journal = Analytical Biochemistry | volume = 540–541 | issue = Supplement C | pages = 38–44 | date = January 2018 | pmid = 29128291 | doi = 10.1016/j.ab.2017.11.003 }}</ref><ref name="Zhu_2017"/> and rs290481T>C<ref name="Zhu_2017" /> polymorphisms.<ref name="Chen_2018" /><ref name="Zhu_2017" /> TCF7L2 rs290481T>C polymorphism, however, has shown no significant correlation to the susceptibility to [[Gestational diabetes|gestational diabetes mellitus (GDM)]] in a Chinese Han population, whereas the T alleles of rs7903146<ref name="Zhu_2017" /> and rs1799884<ref name="Zhang_2013">{{cite journal | vauthors = Zhang C, Bao W, Rong Y, Yang H, Bowers K, Yeung E, Kiely M | title = Genetic variants and the risk of gestational diabetes mellitus: a systematic review | journal = Human Reproduction Update | volume = 19 | issue = 4 | pages = 376–90 | date = 2013-05-19 | pmid = 23690305 | pmc = 3682671 | doi = 10.1093/humupd/dmt013 }}</ref> increase susceptibility to GDM in the Chinese Han population.<ref name="Zhu_2017" /><ref name="Zhang_2013" /> The difference in effects of the different polymorphisms of the gene indicate that the gene is indeed pleiotropic.

== Structure ==
The ''TCF7L2'' gene, encoding the TCF7L2 protein, is located on chromosome 10q25.2-q25.3. The gene contains 19 exons and has autosomal dominant inheritance.<ref name="entrez_gene" /><ref name="OMIM" /> Of the 19 exons, 5 are [[Alternative splicing|alternative]].<ref name="OMIM" /> The TCF7L2 gene contains 619 [[amino acid]]s and its molecular mass is 67919 [[Dalton (unit)|Da]].<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=TCF7L2|title=TCF7L2 Gene - GeneCards {{!}} TF7L2 Protein {{!}} TF7L2 Antibody|last=Database|first=GeneCards Human Gene|website=www.genecards.org|access-date=2017-11-30}}</ref> TCF7L2's secondary structure is a [[helix-turn-helix]] structure.<ref>{{Cite web|url=https://www.uniprot.org/uniprot/Q9NQB0|title=TCF7L2 - Transcription factor 7-like 2 - Homo sapiens (Human) - TCF7L2 gene & protein|website=www.uniprot.org|language=en|access-date=2017-11-30}}</ref>

== Tissue Distribution ==
TCF7L2 does not primarily operate in the β-cells in the pancreas.<ref name="Nobrega_2013">{{cite journal | vauthors = Nobrega MA | title = TCF7L2 and glucose metabolism: time to look beyond the pancreas | journal = Diabetes | volume = 62 | issue = 3 | pages = 706–8 | date = March 2013 | pmid = 23431017 | pmc = 3581232 | doi = 10.2337/db12-1418 }}</ref> It is also expressed in brain, liver, intestine, and fat cells.<ref name="Nobrega_2013" />

== Clinical significance ==

=== Type 2 Diabetes ===

Several single nucleotide polymorphisms within the TCF7L2 gene have been associated with type 2 diabetes. Studies conducted by Ravindranath Duggirala and Michael Stern at The [[University of Texas Health Science Center at San Antonio]] were the first to identify strong [[Genetic linkage|linkage]] for type 2 diabetes at a region on [[Chromosome 10]] in Mexican Americans <ref name="pmid10090898">{{cite journal | vauthors = Duggirala R, Blangero J, Almasy L, Dyer TD, Williams KL, Leach RJ, O'Connell P, Stern MP | title = Linkage of type 2 diabetes mellitus and of age at onset to a genetic location on chromosome 10q in Mexican Americans | journal = American Journal of Human Genetics | volume = 64 | issue = 4 | pages = 1127–40 | date = April 1999 | pmid = 10090898 | pmc = 1377837 | doi=10.1086/302316}}</ref> This signal was later refined by Struan Grant and colleagues at [[DeCODE genetics]] and isolated to the TCF7L2 gene.<ref name="pmid16415884">{{cite journal | vauthors = Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, Helgason A, Stefansson H, Emilsson V, Helgadottir A, Styrkarsdottir U, Magnusson KP, Walters GB, Palsdottir E, Jonsdottir T, Gudmundsdottir T, Gylfason A, Saemundsdottir J, Wilensky RL, Reilly MP, Rader DJ, Bagger Y, Christiansen C, Gudnason V, Sigurdsson G, Thorsteinsdottir U, Gulcher JR, Kong A, Stefansson K | title = Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes | journal = Nature Genetics | volume = 38 | issue = 3 | pages = 320–3 | date = March 2006 | pmid = 16415884 | pmc =  | doi = 10.1038/ng1732 }}</ref> The molecular and physiological mechanisms underlying the association of TCF7L2 with type 2 diabetes are under active investigation, but it is likely that TCF7L2 has important biological roles in multiple metabolic tissues, including the pancreas, liver and adipose tissue.<ref name="Nobrega_2013" /><ref name="pmid27159876">{{cite journal | vauthors = Jin T | title = Current Understanding on Role of the Wnt Signaling Pathway Effector TCF7L2 in Glucose Homeostasis | journal = Endocrine Reviews | volume = 37 | issue = 3 | pages = 254–77 | date = June 2016 | pmid = 27159876 | pmc =  | doi = 10.1210/er.2015-1146 }}</ref> TCF7L2 polymorphisms can increase susceptibility to type 2 diabetes by decreasing the production of [[Glucagon-like peptide-1|glucagon-like peptide-1 (GLP-1)]][[GLP-1|.]]<ref name="Jin_2008"/>

=== Gestational Diabetes (GDM) ===
TCF7L2 modulates [[Pancreatic islets|pancreatic islet]] β-cell function strongly implicating its significant association with [[Gestational diabetes|GDM]] risk.<ref name="Zhang_2013" /> T alleles of rs7903146<ref name="Zhu_2017" /> and rs1799884<ref name="Zhang_2013" /> TCF7L2 polymorphisms increase susceptibility to [[Gestational diabetes|GDM]] in the Chinese Han population.<ref name="Zhu_2017" /><ref name="Zhang_2013" />

=== Cancer ===

TCF7L2 plays a role in [[colorectal cancer]].<ref name="Torres_2017" /> A [[frameshift mutation]] of TCF7L2 provided evidence that TCF7L2 is implicated in colorectal cancer.<ref name="pmid18398040">{{cite journal | vauthors = Slattery ML, Folsom AR, Wolff R, Herrick J, Caan BJ, Potter JD | title = Transcription factor 7-like 2 polymorphism and colon cancer | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 17 | issue = 4 | pages = 978–82 | date = April 2008 | pmid = 18398040 | pmc = 2587179 | doi = 10.1158/1055-9965.EPI-07-2687 }}</ref><ref name="pmid18478343">{{cite journal | vauthors = Hazra A, Fuchs CS, Chan AT, Giovannucci EL, Hunter DJ | title = Association of the TCF7L2 polymorphism with colorectal cancer and adenoma risk | journal = Cancer Causes & Control | volume = 19 | issue = 9 | pages = 975–80 | date = November 2008 | pmid = 18478343 | pmc = 2719293 | doi = 10.1007/s10552-008-9164-3 }}</ref> The silencing of TCF7L2 in [[KM12]] colorectal cancer cells provided evidence that TCF7L2 played a role in [[Cell proliferation|proliferation]] and [[metastasis]] of cancer cells in colorectal cancer.<ref name="Torres_2017" />

Variants of the gene are most likely involved in many other cancer types.<ref name="pmid18621708">{{cite journal | vauthors = Tang W, Dodge M, Gundapaneni D, Michnoff C, Roth M, Lum L | title = A genome-wide RNAi screen for Wnt/beta-catenin pathway components identifies unexpected roles for TCF transcription factors in cancer | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 28 | pages = 9697–702 | date = July 2008 | pmid = 18621708 | pmc = 2453074 | doi = 10.1073/pnas.0804709105 | bibcode = 2008PNAS..105.9697T }}</ref> TCF7L2 is indirectly involved in [[prostate cancer]] through its role in activating the [[PI3K/AKT/mTOR pathway|PI3K/Akt pathway]], a pathway involved in prostate cancer.<ref name="Sun_2006">{{cite journal | vauthors = Sun P, Xiong H, Kim TH, Ren B, Zhang Z | title = Positive inter-regulation between beta-catenin/T cell factor-4 signaling and endothelin-1 signaling potentiates proliferation and survival of prostate cancer cells | journal = Molecular Pharmacology | volume = 69 | issue = 2 | pages = 520–31 | date = February 2006 | pmid = 16291872 | doi = 10.1124/mol.105.019620 }}</ref>

=== Schizophrenia ===
Single nucleotide polymorphisms (SNPs) in TCF7L2 gene have shown an increase in susceptibility to [[schizophrenia]] in Arab, European and Chinese Han populations.<ref name="Liu_2017">{{cite journal | vauthors = Liu L, Li J, Yan M, Li J, Chen J, Zhang Y, Zhu X, Wang L, Kang L, Yuan D, Jin T | title = TCF7L2 polymorphisms and the risk of schizophrenia in the Chinese Han population | journal = Oncotarget | volume = 8 | issue = 17 | pages = 28614–28620 | date = April 2017 | pmid = 28404897 | pmc = 5438676 | doi = 10.18632/oncotarget.15603 }}</ref> In the Chinese Han population, SNP rs12573128<ref name="Liu_2017" /> in TCF7L2 is the variant that was associated with an increase in schizophrenia risk. This marker is used as a pre-diagnostic marker for schizophrenia.<ref name="Liu_2017" />

=== Multiple Sclerosis ===
TCF7L2 is downstream of the [[Wnt signaling pathway|WNT]]/[[Beta-catenin|β-catenin]] pathways. The activation of the WNT/β-catenin pathways have been associated [[demyelination]] in [[multiple sclerosis]].<ref name="Vallée_2017" /> TCF7L2 is unregulated during early r[[Remyelination|emyelination]], leading scientists to believe that it is involved in [[remyelination]].<ref name="Vallée_2017" /> TCF7L2 could act in dependence or independent of the WNT/β-catenin pathways.<ref name="Vallée_2017">{{cite journal | vauthors = Vallée A, Vallée JN, Guillevin R, Lecarpentier Y | title = Interactions Between the Canonical WNT/Beta-Catenin Pathway and PPAR Gamma on Neuroinflammation, Demyelination, and Remyelination in Multiple Sclerosis | journal = Cellular and Molecular Neurobiology | date = September 2017 | pmid = 28905149 | doi = 10.1007/s10571-017-0550-9 }}</ref>

== Model organisms ==

[[Model organism]]s have been used in the study of TCF7L2 function. A conditional [[knockout mouse]] line called ''Tcf7l2<sup>tm1a(EUCOMM)Wtsi</sup>'' was generated at the [[Wellcome Trust Sanger Institute]].<ref name="mgp_reference">{{cite journal |title=The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice | vauthors = Gerdin AK |year=2010 |journal=Acta Ophthalmologica|volume=88 |pages=925–7|doi=10.1111/j.1755-3768.2010.4142.x }}</ref> Male and female animals underwent a standardized [[phenotypic screen]]<ref name="IMPCsearch_ref">{{cite web |url=http://www.mousephenotype.org/data/search?q=Tcf7l2#fq=*:*&facet=gene |title=International Mouse Phenotyping Consortium}}</ref> to determine the effects of deletion.<ref name="pmid21677750">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = June 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = June 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = January 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref><ref name="pmid23870131">{{cite journal | vauthors = White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP | title = Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes | journal = Cell | volume = 154 | issue = 2 | pages = 452–64 | date = July 2013 | pmid = 23870131 | pmc = 3717207 | doi = 10.1016/j.cell.2013.06.022 }}</ref> Additional screens performed:  - In-depth immunological phenotyping<ref name="iii_ref">{{cite web |url= http://www.immunophenotyping.org/data/search?keys=Tcf7l2&field_gene_construct_tid=All |title=Infection and Immunity Immunophenotyping (3i) Consortium}}</ref>

Variations of the protein encoding gene are found in rats, zebra fish, drosophila, and budding yeast.<ref>{{Cite web|url=http://marrvel.org/search/gene/TCF7L2|title=MARRVEL: Search Result|website=marrvel.org|access-date=2017-11-30}}</ref> Therefore, all of those organisms can be used as model organisms in the study of TCF7L2 function. {{clear|left}}
			
== Nomenclature ==

TCF7L2 is the symbol officially approved by the [[HUGO Gene Nomenclature Committee]] for the [[TCF4|transcription factor 4]] gene (TCF4).

== See also ==
*[[TCF/LEF family]]
{{clear}}

== References ==
{{Reflist|33em}}

== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Segditsas S, Tomlinson I | title = Colorectal cancer and genetic alterations in the Wnt pathway | journal = Oncogene | volume = 25 | issue = 57 | pages = 7531–7 | date = December 2006 | pmid = 17143297 | doi = 10.1038/sj.onc.1210059 }}
* {{cite journal | vauthors = Florez JC | title = The new type 2 diabetes gene TCF7L2 | journal = Current Opinion in Clinical Nutrition and Metabolic Care | volume = 10 | issue = 4 | pages = 391–6 | date = July 2007 | pmid = 17563454 | doi = 10.1097/MCO.0b013e3281e2c9be }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B, Clevers H | title = Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma | journal = Science | volume = 275 | issue = 5307 | pages = 1784–7 | date = March 1997 | pmid = 9065401 | doi = 10.1126/science.275.5307.1784 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW | title = Identification of c-MYC as a target of the APC pathway | journal = Science | volume = 281 | issue = 5382 | pages = 1509–12 | date = September 1998 | pmid = 9727977 | doi = 10.1126/science.281.5382.1509 | bibcode = 1998Sci...281.1509H }}
* {{cite journal | vauthors = Barker N, Huls G, Korinek V, Clevers H | title = Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium | journal = The American Journal of Pathology | volume = 154 | issue = 1 | pages = 29–35 | date = January 1999 | pmid = 9916915 | pmc = 1853446 | doi = 10.1016/S0002-9440(10)65247-9 }}
* {{cite journal | vauthors = Omer CA, Miller PJ, Diehl RE, Kral AM | title = Identification of Tcf4 residues involved in high-affinity beta-catenin binding | journal = Biochemical and Biophysical Research Communications | volume = 256 | issue = 3 | pages = 584–90 | date = March 1999 | pmid = 10080941 | doi = 10.1006/bbrc.1999.0379 }}
* {{cite journal | vauthors = Giannini AL, Vivanco MM, Kypta RM | title = Analysis of beta-catenin aggregation and localization using GFP fusion proteins: nuclear import of alpha-catenin by the beta-catenin/Tcf complex | journal = Experimental Cell Research | volume = 255 | issue = 2 | pages = 207–20 | date = March 2000 | pmid = 10694436 | doi = 10.1006/excr.1999.4785 }}
* {{cite journal | vauthors = Duval A, Busson-Leconiat M, Berger R, Hamelin R | title = Assignment of the TCF-4 gene (TCF7L2) to human chromosome band 10q25.3 | journal = Cytogenetics and Cell Genetics | volume = 88 | issue = 3–4 | pages = 264–5 | year = 2000 | pmid = 10828605 | doi = 10.1159/000015534 }}
* {{cite journal | vauthors = Duval A, Rolland S, Tubacher E, Bui H, Thomas G, Hamelin R | title = The human T-cell transcription factor-4 gene: structure, extensive characterization of alternative splicings, and mutational analysis in colorectal cancer cell lines | journal = Cancer Research | volume = 60 | issue = 14 | pages = 3872–9 | date = July 2000 | pmid = 10919662 | doi =  }}
* {{cite journal | vauthors = Brantjes H, Roose J, van De Wetering M, Clevers H | title = All Tcf HMG box transcription factors interact with Groucho-related co-repressors | journal = Nucleic Acids Research | volume = 29 | issue = 7 | pages = 1410–9 | date = April 2001 | pmid = 11266540 | pmc = 31284 | doi = 10.1093/nar/29.7.1410 }}
* {{cite journal | vauthors = Palacino JJ, Murphy MP, Murayama O, Iwasaki K, Fujiwara M, Takashima A, Golde TE, Wolozin B | title = Presenilin 1 regulates beta-catenin-mediated transcription in a glycogen synthase kinase-3-independent fashion | journal = The Journal of Biological Chemistry | volume = 276 | issue = 42 | pages = 38563–9 | date = October 2001 | pmid = 11504726 | doi = 10.1074/jbc.M105376200 }}
* {{cite journal | vauthors = Miravet S, Piedra J, Miró F, Itarte E, García de Herreros A, Duñach M | title = The transcriptional factor Tcf-4 contains different binding sites for beta-catenin and plakoglobin | journal = The Journal of Biological Chemistry | volume = 277 | issue = 3 | pages = 1884–91 | date = January 2002 | pmid = 11711551 | doi = 10.1074/jbc.M110248200 | pmc = 5009259 }}
* {{cite journal | vauthors = Graham TA, Ferkey DM, Mao F, Kimelman D, Xu W | title = Tcf4 can specifically recognize beta-catenin using alternative conformations | journal = Nature Structural Biology | volume = 8 | issue = 12 | pages = 1048–52 | date = December 2001 | pmid = 11713475 | doi = 10.1038/nsb718 }}
* {{cite journal | vauthors = Poy F, Lepourcelet M, Shivdasani RA, Eck MJ | title = Structure of a human Tcf4-beta-catenin complex | journal = Nature Structural Biology | volume = 8 | issue = 12 | pages = 1053–7 | date = December 2001 | pmid = 11713476 | doi = 10.1038/nsb720 }}
* {{cite journal | vauthors = Thiele A, Wasner M, Müller C, Engeland K, Hauschildt S | title = Regulation and possible function of beta-catenin in human monocytes | journal = Journal of Immunology | volume = 167 | issue = 12 | pages = 6786–93 | date = December 2001 | pmid = 11739494 | doi = 10.4049/jimmunol.167.12.6786 }}
* {{cite journal | vauthors = Marchenko GN, Marchenko ND, Leng J, Strongin AY | title = Promoter characterization of the novel human matrix metalloproteinase-26 gene: regulation by the T-cell factor-4 implies specific expression of the gene in cancer cells of epithelial origin | journal = The Biochemical Journal | volume = 363 | issue = Pt 2 | pages = 253–62 | date = April 2002 | pmid = 11931652 | pmc = 1222473 | doi = 10.1042/0264-6021:3630253 }}
* {{cite journal | vauthors = Leung JY, Kolligs FT, Wu R, Zhai Y, Kuick R, Hanash S, Cho KR, Fearon ER | title = Activation of AXIN2 expression by beta-catenin-T cell factor. A feedback repressor pathway regulating Wnt signaling | journal = The Journal of Biological Chemistry | volume = 277 | issue = 24 | pages = 21657–65 | date = June 2002 | pmid = 11940574 | doi = 10.1074/jbc.M200139200 }}
{{refend}}

==External links ==

* TCF7L2 here called TCF4 features on this Wnt pathway web site: [http://www.stanford.edu/~rnusse/pathways/cell2.html Wnt signalling molecules] [http://www.stanford.edu/~rnusse/axindshtcf/tcf2.html TCFs]
* Structure determination of TCF7L2: [http://www.rcsb.org/pdb/explore.do?structureId=2GL7 PDB entry 2GL7] and related publication on [https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pubmed&term=Crystal%20Structure%20of%20a%20beta-Catenin/BCL9/Tcf4%20Complex PubMed]
* PubMed GeneRIFs (summaries of related scientific publications) - [https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=gene_full_report&db=gene&cmd=Display&dopt=gene_pubmed_rif&from_uid=6934]
* Weizmann Institute GeneCard for [https://www.genecards.org/cgi-bin/carddisp.pl?gene=TCF7L2&search=tcf7l2 TCF7L2]

{{PDB Gallery|geneid=6934}}
{{Signaling proteins}}
{{Transcription factors|g4}}

[[Category:Transcription factors]]
[[Category:Signal transduction]]
[[Category:Gene expression]]