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HNF1A  -  HNF1 homeobox A

Homo sapiens

Synonyms: HNF-1-alpha, HNF-1A, HNF1, Hepatocyte nuclear factor 1-alpha, IDDM20, ...
 
 
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Disease relevance of TCF1

 

High impact information on TCF1

 

Chemical compound and disease context of TCF1

 

Biological context of TCF1

  • METHODS: At first, a series of 10 adenomas and 29 colon cancers regardless of microsatellite instability status were screened for TCF1 mutations on the entire coding sequence [13].
  • Ten exons and flanking introns of TCF1 of these patients were directly sequenced for mutations [4].
  • The TCF1 gene was found to be located on chromosome 12 in both man and rat, thereby defining a new segment of homology between these two species (and a segment of mouse chromosome 5) [14].
  • The phenotype and clinical profile of some of the studied patients is compatible with that of patients carrying mutations in the TCF1 or TCF14 genes, while others may carry mutations in different loci [15].
  • The results also showed that sFRP3 treatment attenuates some of the observed Wnt 3a effects on MSCs, and that inhibition of canonical Wnt signaling using a dominant negative TCF1 enhances MSC osteogenesis [16].
 

Anatomical context of TCF1

  • Here we show that subjects with the MODY3-form of NIDDM have mutations in the gene encoding hepatocyte nuclear factor-1alpha (HNF-1alpha, which is encoded by the gene TCF1) [17].
  • The mechanisms by which mutations in the HNF-1alpha gene cause diabetes mellitus are unclear but might include abnormal pancreatic islet development during foetal life thereby limiting their later function, as well as impaired transcriptional regulation of genes that play a key role in normal pancreatic beta cell function [18].
  • The human T cell transcription factor-1 gene. Structure, localization, and promoter characterization [19].
  • PUFA repress the promoter activity only in HNF4 alpha-cotransfected HeLa cells, whereas they have no effects on the promoter activity in HNF1 alpha-cotransfected HeLa cells [20].
  • We identified hepatic nuclear factor 1 (HNF1) as an important liver-specific trans-acting element for the human ACAT2 gene using the human hepatocellular carcinoma cell lines HuH7 and HepG2 [21].
 

Associations of TCF1 with chemical compounds

 

Physical interactions of TCF1

 

Regulatory relationships of TCF1

 

Other interactions of TCF1

  • Functional studies of R137-K161del HNF-1beta revealed that it could not bind an HNF-1 target sequence or stimulate transcription of a reporter gene indicating that this is a loss-of-function mutation [36].
  • The relative proportions classified as diabetic depended on whether fasting (38 % vs 22 %, glucokinase vs HNF-1 alpha) or 2-h values (19 % vs 44 %) were used [37].
  • Control of ACAT2 liver expression by HNF1 [21].
  • Differential activation of intestinal gene promoters: functional interactions between GATA-5 and HNF-1 alpha [38].
  • This study demonstrates for the first time DCoH/HNF-1 alpha expression and transcriptional activity in human epidermal melanocytes in vitro and in situ and identified tyrosinase, the key enzyme for pigmentation, as a new transcriptional target [39].
 

Analytical, diagnostic and therapeutic context of TCF1

  • Glucokinase subjects had a higher FPG than HNF-1 alpha subjects ([means +/- SD] 6.8 +/- 0.8 vs 6.0 +/- 1.9 mmol/l, p < 0.0001), a lower 2-h value (8.9 +/- 2.3 vs 11.2 +/- 5.2 mmol/l, p < 0.0001) and a lower OGTT increment (2-h - fasting) (2.1 +/- 2.3 vs 5.2 +/- 3.9 mmol/l, p < 0.0001) [37].
  • By gel retardation assays with synthetic oligonucleotides, at least two distinct liver nuclear factors were identified, HNF-1 and HNF-2 (hepatocyte nuclear factors), which bound specifically to the first and second region, respectively [40].
  • Administration of glucose by intravenous infusion for 42 h resulted in a significant increase in the amount of insulin secreted over the 5-9 mmol/l glucose concentration range in the control subjects and nondiabetic MODY3 subjects (by 38 and 35%, respectively), but no significant change was observed in the diabetic MODY3 subjects [41].
  • METHODS: To assess the consequence of potential HNF-1 alpha splice site mutations we developed a nested reverse transcriptase PCR (RT-PCR) assay for the amplification of illegitimate HNF-1 alpha transcripts in Epstein Barr virus transformed lymphoblastoid cell lines [42].
  • On Western blots of colorectal cancer cells, the TCF-1-specific monoclonal antibody 7H3 detected a similar heterogeneous spectrum of TCF-1 specific polypeptide chains [43].

References

  1. Bi-allelic inactivation of TCF1 in hepatic adenomas. Bluteau, O., Jeannot, E., Bioulac-Sage, P., Marqués, J.M., Blanc, J.F., Bui, H., Beaudoin, J.C., Franco, D., Balabaud, C., Laurent-Puig, P., Zucman-Rossi, J. Nat. Genet. (2002) [Pubmed]
  2. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Boyault, S., Rickman, D.S., de Reyni??s, A., Balabaud, C., Rebouissou, S., Jeannot, E., H??rault, A., Saric, J., Belghiti, J., Franco, D., Bioulac-Sage, P., Laurent-Puig, P., Zucman-Rossi, J. Hepatology (2007) [Pubmed]
  3. Identification of seven novel nucleotide variants in the hepatocyte nuclear factor-1alpha (TCF1) promoter region in MODY patients. Godart, F., Bellanné-Chantelot, C., Clauin, S., Gragnoli, C., Abderrahmani, A., Blanché, H., Boutin, P., Chèvre, J.C., Froguel, P., Bailleul, B. Hum. Mutat. (2000) [Pubmed]
  4. High frequency of mutations in the HNF-1alpha gene in non-obese patients with diabetes of youth in Japanese and identification of a case of digenic inheritance. Tonooka, N., Tomura, H., Takahashi, Y., Onigata, K., Kikuchi, N., Horikawa, Y., Mori, M., Takeda, J. Diabetologia (2002) [Pubmed]
  5. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Prokunina, L., Castillejo-López, C., Oberg, F., Gunnarsson, I., Berg, L., Magnusson, V., Brookes, A.J., Tentler, D., Kristjansdóttir, H., Gröndal, G., Bolstad, A.I., Svenungsson, E., Lundberg, I., Sturfelt, G., Jönssen, A., Truedsson, L., Lima, G., Alcocer-Varela, J., Jonsson, R., Gyllensten, U.B., Harley, J.B., Alarcón-Segovia, D., Steinsson, K., Alarcón-Riquelme, M.E. Nat. Genet. (2002) [Pubmed]
  6. Mapping of a gene for type 2 diabetes associated with an insulin secretion defect by a genome scan in Finnish families. Mahtani, M.M., Widén, E., Lehto, M., Thomas, J., McCarthy, M., Brayer, J., Bryant, B., Chan, G., Daly, M., Forsblom, C., Kanninen, T., Kirby, A., Kruglyak, L., Munnelly, K., Parkkonen, M., Reeve-Daly, M.P., Weaver, A., Brettin, T., Duyk, G., Lander, E.S., Groop, L.C. Nat. Genet. (1996) [Pubmed]
  7. Transcription factor p91 interacts with the epidermal growth factor receptor and mediates activation of the c-fos gene promoter. Fu, X.Y., Zhang, J.J. Cell (1993) [Pubmed]
  8. Genetic and clinical characteristics of maturity-onset diabetes of the young in Chinese patients. Xu, J.Y., Dan, Q.H., Chan, V., Wat, N.M., Tam, S., Tiu, S.C., Lee, K.F., Siu, S.C., Tsang, M.W., Fung, L.M., Chan, K.W., Lam, K.S. Eur. J. Hum. Genet. (2005) [Pubmed]
  9. Molecular targets of a human HNF1 alpha mutation responsible for pancreatic beta-cell dysfunction. Wang, H., Antinozzi, P.A., Hagenfeldt, K.A., Maechler, P., Wollheim, C.B. EMBO J. (2000) [Pubmed]
  10. Positive regulation of the vHNF1 promoter by the orphan receptors COUP-TF1/Ear3 and COUP-TFII/Arp1. Power, S.C., Cereghini, S. Mol. Cell. Biol. (1996) [Pubmed]
  11. Hepatocyte nuclear factor 1 alpha: a key mediator of the effect of bile acids on gene expression. Jung, D., Kullak-Ublick, G.A. Hepatology (2003) [Pubmed]
  12. Pancreatic islet expression studies and polymorphic DNA markers in the genes encoding hepatocyte nuclear factor-3alpha, -3beta, -3gamma, -4gamma, and -6. Vaisse, C., Kim, J., Espinosa, R., Le Beau, M.M., Stoffel, M. Diabetes (1997) [Pubmed]
  13. Frequent mutations of hepatocyte nuclear factor 1 in colorectal cancer with microsatellite instability. Laurent-Puig, P., Plomteux, O., Bluteau, O., Zinzindohoué, F., Jeannot, E., Dahan, K., Kartheuser, A., Chapusot, C., Cugnenc, P.H., Zucman-Rossi, J. Gastroenterology (2003) [Pubmed]
  14. Chromosomal localization in man and rat of the genes encoding the liver-enriched transcription factors C/EBP, DBP, and HNF1/LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF). Szpirer, C., Riviere, M., Cortese, R., Nakamura, T., Islam, M.Q., Levan, G., Szpirer, J. Genomics (1992) [Pubmed]
  15. Analysis of the glucokinase gene in Mexican families displaying early-onset non-insulin-dependent diabetes mellitus including MODY families. del Bosque-Plata, L., García-García, E., Ramírez-Jiménez, S., Cabello-Villegas, J., Riba, L., Gómez-León, A., Vega-Hernández, G., Altamirano-Bustamante, N., Calzada-León, R., Robles-Valdés, C., Mendoza-Morfín, F., Curiel-Pérez, O., Tusié-Luna, M.T. Am. J. Med. Genet. (1997) [Pubmed]
  16. Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. Boland, G.M., Perkins, G., Hall, D.J., Tuan, R.S. J. Cell. Biochem. (2004) [Pubmed]
  17. Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). Yamagata, K., Oda, N., Kaisaki, P.J., Menzel, S., Furuta, H., Vaxillaire, M., Southam, L., Cox, R.D., Lathrop, G.M., Boriraj, V.V., Chen, X., Cox, N.J., Oda, Y., Yano, H., Le Beau, M.M., Yamada, S., Nishigori, H., Takeda, J., Fajans, S.S., Hattersley, A.T., Iwasaki, N., Hansen, T., Pedersen, O., Polonsky, K.S., Bell, G.I. Nature (1996) [Pubmed]
  18. Identification of nine novel mutations in the hepatocyte nuclear factor 1 alpha gene associated with maturity-onset diabetes of the young (MODY3). Vaxillaire, M., Rouard, M., Yamagata, K., Oda, N., Kaisaki, P.J., Boriraj, V.V., Chevre, J.C., Boccio, V., Cox, R.D., Lathrop, G.M., Dussoix, P., Philippe, J., Timsit, J., Charpentier, G., Velho, G., Bell, G.I., Froguel, P. Hum. Mol. Genet. (1997) [Pubmed]
  19. The human T cell transcription factor-1 gene. Structure, localization, and promoter characterization. van de Wetering, M., Oosterwegel, M., Holstege, F., Dooyes, D., Suijkerbuijk, R., Geurts van Kessel, A., Clevers, H. J. Biol. Chem. (1992) [Pubmed]
  20. Polyunsaturated fatty acyl coenzyme A suppress the glucose-6-phosphatase promoter activity by modulating the DNA binding of hepatocyte nuclear factor 4 alpha. Rajas, F., Gautier, A., Bady, I., Montano, S., Mithieux, G. J. Biol. Chem. (2002) [Pubmed]
  21. Control of ACAT2 liver expression by HNF1. Pramfalk, C., Davis, M.A., Eriksson, M., Rudel, L.L., Parini, P. J. Lipid Res. (2005) [Pubmed]
  22. Polymorphic variations in the neurogenic differentiation-1, neurogenin-3, and hepatocyte nuclear factor-1alpha genes contribute to glucose intolerance in a South Indian population. Jackson, A.E., Cassell, P.G., North, B.V., Vijayaraghavan, S., Gelding, S.V., Ramachandran, A., Snehalatha, C., Hitman, G.A. Diabetes (2004) [Pubmed]
  23. Identification and functional characterization of a novel mutation of hepatocyte nuclear factor-1alpha gene in a Korean family with MODY3. Kim, K.A., Kang, K., Chi, Y.I., Chang, I., Lee, M.K., Kim, K.W., Shoelson, S.E., Lee, M.S. Diabetologia (2003) [Pubmed]
  24. Liver and kidney function in Japanese patients with maturity-onset diabetes of the young. Iwasaki, N., Ogata, M., Tomonaga, O., Kuroki, H., Kasahara, T., Yano, N., Iwamoto, Y. Diabetes Care (1998) [Pubmed]
  25. Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young. Ellard, S., Colclough, K. Hum. Mutat. (2006) [Pubmed]
  26. Association of I27L polymorphism of hepatocyte nuclear factor-1 alpha gene with high-density lipoprotein cholesterol level. Babaya, N., Ikegami, H., Fujisawa, T., Nojima, K., Itoi-Babaya, M., Inoue, K., Nakura, J., Abe, M., Yamamoto, M., Jin, J.J., Wu, Z., Miki, T., Fukuda, M., Ogihara, T. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  27. Activation of nicotinamide N-methyltransferase gene promoter by hepatocyte nuclear factor-1beta in human papillary thyroid cancer cells. Xu, J., Capezzone, M., Xu, X., Hershman, J.M. Mol. Endocrinol. (2005) [Pubmed]
  28. The bifunctional DCOH protein binds to HNF1 independently of its 4-alpha-carbinolamine dehydratase activity. Sourdive, D.J., Transy, C., Garbay, S., Yaniv, M. Nucleic Acids Res. (1997) [Pubmed]
  29. Bcr interferes with beta-catenin-Tcf1 interaction. Ress, A., Moelling, K. FEBS Lett. (2006) [Pubmed]
  30. Multiple NF-{kappa}B and IFN Regulatory Factor Family Transcription Factors Regulate CCL19 Gene Expression in Human Monocyte-Derived Dendritic Cells. Pietil??, T.E., Veckman, V., Lehtonen, A., Lin, R., Hiscott, J., Julkunen, I. J. Immunol. (2007) [Pubmed]
  31. SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4. Wang, J.C., Stafford, J.M., Granner, D.K. J. Biol. Chem. (1998) [Pubmed]
  32. Transcription factor BACH2 is transcriptionally regulated by the BCR/ABL oncogene. Vieira, S.A., Deininger, M.W., Sorour, A., Sinclair, P., Foroni, L., Goldman, J.M., Melo, J.V. Genes Chromosomes Cancer (2001) [Pubmed]
  33. Involvement of hepatocyte nuclear factor 1 in the regulation of the UDP-glucuronosyltransferase 1A7 (UGT1A7) gene in rat hepatocytes. Metz, R.P., Auyeung, D.J., Kessler, F.K., Ritter, J.K. Mol. Pharmacol. (2000) [Pubmed]
  34. In vitro selection and characterization of TCF-1 binding RNA aptamers. Lee, S.Y., Jeong, S. Mol. Cells (2004) [Pubmed]
  35. X-ray crystal structure of IRF-3 and its functional implications. Takahasi, K., Suzuki, N.N., Horiuchi, M., Mori, M., Suhara, W., Okabe, Y., Fukuhara, Y., Terasawa, H., Akira, S., Fujita, T., Inagaki, F. Nat. Struct. Biol. (2003) [Pubmed]
  36. A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1beta. Lindner, T.H., Njolstad, P.R., Horikawa, Y., Bostad, L., Bell, G.I., Sovik, O. Hum. Mol. Genet. (1999) [Pubmed]
  37. The genetic abnormality in the beta cell determines the response to an oral glucose load. Stride, A., Vaxillaire, M., Tuomi, T., Barbetti, F., Njølstad, P.R., Hansen, T., Costa, A., Conget, I., Pedersen, O., Søvik, O., Lorini, R., Groop, L., Froguel, P., Hattersley, A.T. Diabetologia (2002) [Pubmed]
  38. Differential activation of intestinal gene promoters: functional interactions between GATA-5 and HNF-1 alpha. Krasinski, S.D., Van Wering, H.M., Tannemaat, M.R., Grand, R.J. Am. J. Physiol. Gastrointest. Liver Physiol. (2001) [Pubmed]
  39. In situ and in vitro evidence for DCoH/HNF-1 alpha transcription of tyrosinase in human skin melanocytes. Schallreuter, K.U., Kothari, S., Hasse, S., Kauser, S., Lindsey, N.J., Gibbons, N.C., Hibberts, N., Wood, J.M. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  40. Multiple hepatic trans-acting factors are required for in vitro transcription of the human alpha-1-antitrypsin gene. Li, Y., Shen, R.F., Tsai, S.Y., Woo, S.L. Mol. Cell. Biol. (1988) [Pubmed]
  41. Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome 12. Byrne, M.M., Sturis, J., Menzel, S., Yamagata, K., Fajans, S.S., Dronsfield, M.J., Bain, S.C., Hattersley, A.T., Velho, G., Froguel, P., Bell, G.I., Polonsky, K.S. Diabetes (1996) [Pubmed]
  42. Abnormal splicing of hepatocyte nuclear factor 1 alpha in maturity-onset diabetes of the young. Bulman, M.P., Harries, L.W., Hansen, T., Shepherd, M., Kelly, W.F., Hattersley, A.T., Ellard, S. Diabetologia (2002) [Pubmed]
  43. Ectopic activation of lymphoid high mobility group-box transcription factor TCF-1 and overexpression in colorectal cancer cells. Mayer, K., Hieronymus, T., Castrop, J., Clevers, H., Ballhausen, W.G. Int. J. Cancer (1997) [Pubmed]
 
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