TCF7L1

Transcription factor 7-like 1 (T-cell specific, HMG-box)
Identifiers
Symbols	TCF7L1 ; TCF-3; TCF3
External IDs	OMIM: 604652 HomoloGene: 7563 GeneCards: TCF7L1 Gene
Gene ontology Molecular function • DNA binding • chromatin binding • transcription factor activity, sequence-specific DNA binding • beta-catenin binding • sequence-specific DNA binding • transcription regulatory region DNA binding Cellular component • nucleus • nucleoplasm • transcription factor complex Biological process • chromatin organization • transcription, DNA-templated • regulation of transcription, DNA-templated • regulation of transcription from RNA polymerase II promoter • anterior/posterior axis specification, embryo • regulation of Wnt signaling pathway • somatic stem cell maintenance • skin development • negative regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter during mitosis • axial mesoderm morphogenesis • generation of neurons • canonical Wnt signaling pathway • regulation of stem cell maintenance Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	83439	21415
Ensembl	ENSG00000152284	ENSMUSG00000055799
UniProt	Q9HCS4	Q9Z1J1
RefSeq (mRNA)	NM_031283	NM_001079822
RefSeq (protein)	NP_112573	NP_001073290
Location (UCSC)	Chr 2: 85.13 – 85.31 Mb	Chr 6: 72.63 – 72.79 Mb
PubMed search

transcription factor 7-like 1 (T-cell specific, HMG-box), also known as TCF7L1, is a human gene.^[1]

This gene encodes a member of the T cell factor/lymphoid enhancer factor family of transcription factors. These transcription factors are activated by beta catenin, mediate the Wnt signaling pathway and are antagonized by the transforming growth factor beta signaling pathway. The encoded protein contains a high mobility group-box DNA binding domain and participates in the regulation of cell cycle genes and cellular senescence.^[1]

Model organisms

Tcf7l1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Salmonella infection	Normal[2]
Citrobacter infection	Normal[3]
All tests and analysis from[4][5]

Model organisms have been used in the study of TCF7L1 function. A conditional knockout mouse line, called Tcf7l1^{tm1a(EUCOMM)Wtsi[6][7]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.^[8][9][10]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[4][11] Twenty four tests were carried out on mutant mice and two significant abnormalities were observed.^[4] Few homozygous mutant embryos were identified during gestation, and those that did survive had a severe craniofacial defect. None survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals.^[4]

References

1. "Entrez Gene: transcription factor 7-like 1 (T-cell specific, HMG-box)". Retrieved 2011-08-30.
2. "Salmonella infection data for Tcf7l1". Wellcome Trust Sanger Institute.
3. "Citrobacter infection data for Tcf7l1". Wellcome Trust Sanger Institute.
4. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
5. Mouse Resources Portal, Wellcome Trust Sanger Institute.
6. "International Knockout Mouse Consortium".
7. "Mouse Genome Informatics".
8. 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 (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
9. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
10. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
11. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Castrop J, van Norren K, Clevers H (Feb 1992). "A gene family of HMG-box transcription factors with homology to TCF-1". Nucleic Acids Research 20 (3): 611. doi:10.1093/nar/20.3.611. PMC 310434. PMID 1741298.
• Sagara N, Katoh M (Nov 2000). "Mitomycin C resistance induced by TCF-3 overexpression in gastric cancer cell line MKN28 is associated with DT-diaphorase down-regulation". Cancer Research 60 (21): 5959–62. PMID 11085512.
• Kim TW, Kim HJ, Lee C, Kim HY, Baek SH, Kim JH, Kwon KS, Kim JR (Apr 2008). "Identification of replicative senescence-associated genes in human umbilical vein endothelial cells by an annealing control primer system". Experimental Gerontology 43 (4): 286–95. doi:10.1016/j.exger.2007.12.010. PMID 18258400.
• Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR. "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score". Molecular Medicine 16 (7-8): 247–53. doi:10.2119/molmed.2009.00159. PMC 2896464. PMID 20379614.
• Katoh M (Jan 2007). "Networking of WNT, FGF, Notch, BMP, and Hedgehog signaling pathways during carcinogenesis". Stem Cell Reviews 3 (1): 30–8. doi:10.1007/s12015-007-0006-6. PMID 17873379.
• Filleur S, Hirsch J, Wille A, Schön M, Sell C, Shearer MH, Nelius T, Wieland I (2009). "INTS6/DICE1 inhibits growth of human androgen-independent prostate cancer cells by altering the cell cycle profile and Wnt signaling". Cancer Cell International 9: 28. doi:10.1186/1475-2867-9-28. PMC 2779787. PMID 19906297.
• Balaz P, Plaschke J, Krüger S, Görgens H, Schackert HK (Aug 2010). "TCF-3, 4 protein expression correlates with beta-catenin expression in MSS and MSI-H colorectal cancer from HNPCC patients but not in sporadic colorectal cancers". International Journal of Colorectal Disease 25 (8): 931–9. doi:10.1007/s00384-010-0959-9. PMID 20532534.
• Salins P, Shawesh S, He Y, Dibrov A, Kashour T, Arthur G, Amara F (Feb 2007). "Lovastatin protects human neurons against Abeta-induced toxicity and causes activation of beta-catenin-TCF/LEF signaling". Neuroscience Letters 412 (3): 211–6. doi:10.1016/j.neulet.2006.07.045. PMID 17234346.
• Halatsch ME, Löw S, Mursch K, Hielscher T, Schmidt U, Unterberg A, Vougioukas VI, Feuerhake F (Aug 2009). "Candidate genes for sensitivity and resistance of human glioblastoma multiforme cell lines to erlotinib. Laboratory investigation". Journal of Neurosurgery 111 (2): 211–8. doi:10.3171/2008.9.JNS08551. PMID 19301967.
• Barker N, Huls G, Korinek V, Clevers H (Jan 1999). "Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium". The American Journal of Pathology 154 (1): 29–35. doi:10.1016/S0002-9440(10)65247-9. PMC 1853446. PMID 9916915.
• Velasco J, Zarrabeitia MT, Prieto JR, Perez-Castrillon JL, Perez-Aguilar MD, Perez-Nuñez MI, Sañudo C, Hernandez-Elena J, Calvo I, Ortiz F, Gonzalez-Macias J, Riancho JA (Jan 2010). "Wnt pathway genes in osteoporosis and osteoarthritis: differential expression and genetic association study". Osteoporosis International 21 (1): 109–18. doi:10.1007/s00198-009-0931-0. PMID 19373426.
• Graham TA, Weaver C, Mao F, Kimelman D, Xu W (Dec 2000). "Crystal structure of a beta-catenin/Tcf complex". Cell 103 (6): 885–96. doi:10.1016/S0092-8674(00)00192-6. PMID 11136974.
• Lukas J, Mazna P, Valenta T, Doubravska L, Pospichalova V, Vojtechova M, Fafilek B, Ivanek R, Plachy J, Novak J, Korinek V (May 2009). "Dazap2 modulates transcription driven by the Wnt effector TCF-4". Nucleic Acids Research 37 (9): 3007–20. doi:10.1093/nar/gkp179. PMC 2685103. PMID 19304756.
• Ollila HM, Soronen P, Silander K, Palo OM, Kieseppä T, Kaunisto MA, Lönnqvist J, Peltonen L, Partonen T, Paunio T (Apr 2009). "Findings from bipolar disorder genome-wide association studies replicate in a Finnish bipolar family-cohort". Molecular Psychiatry 14 (4): 351–3. doi:10.1038/mp.2008.122. PMC 2694406. PMID 19308021.
• Pollheimer J, Loregger T, Sonderegger S, Saleh L, Bauer S, Bilban M, Czerwenka K, Husslein P, Knöfler M (Apr 2006). "Activation of the canonical wingless/T-cell factor signaling pathway promotes invasive differentiation of human trophoblast". The American Journal of Pathology 168 (4): 1134–47. doi:10.2353/ajpath.2006.050686. PMC 1606554. PMID 16565489.
• Brantjes H, Roose J, van De Wetering M, Clevers H (Apr 2001). "All Tcf HMG box transcription factors interact with Groucho-related co-repressors". Nucleic Acids Research 29 (7): 1410–9. doi:10.1093/nar/29.7.1410. PMC 31284. PMID 11266540.