Hnf1α (MODY3) controls tissue-specific transcriptional programs and exerts opposed effects on cell growth in pancreatic islets and liver

Molecular and Cellular Biology

Volumn 29, Issue 11, 2009, Pages 2945-2959

  Servitja, Joan Marc ^a,b   Pignatelli, Miguel ^c,g   Maestro, Miguel Ángel ^a,b   Cardalda, Carina ^a   Boj, Sylvia F ^a   Lozano, Juanjo ^c   Blanco, Enrique ^c   Lafuente, Amàlia ^d   McCarthy, Mark I ^e   Sumoy, Lauro ^c   Guigó, Roderic ^c   Ferrer, Jorge ^a,b,f  

^a ALBA SYNCHROTRON LIGHT SOURCE   (Spain)

^b INSTITUTO DE SALUD CARLOS III   (Spain)

^c CENTRE FOR GENOMIC REGULATION CRG   (Spain)

^d UNIVERSITY OF BARCELONA   (Spain)

^e UNIVERSITY OF OXFORD   (United Kingdom)

^f HOSPITAL CLÍNIC   (Spain)

^g UNIVERSITY OF VALENCIA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

HEPATOCYTE NUCLEAR FACTOR 1ALPHA; HEPATOCYTE NUCLEAR FACTOR 1BETA; MESSENGER RNA; T LYMPHOCYTE ANTIGEN; TCF1 PROTEIN, MOUSE; TCF2 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARCINOGENESIS; CELL GROWTH; CONTROLLED STUDY; DOWN REGULATION; GENE EXPRESSION; GENE TARGETING; GENETIC TRANSCRIPTION; GLUCOSE METABOLISM; INSULINOMA; LIVER CELL; MALE; MOUSE; NONHUMAN; PANCREAS ISLET BETA CELL; PLEIOTROPY; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEFICIENCY; PROTEIN FUNCTION; PROTEIN MOTIF; TRANSCRIPTION REGULATION; UPREGULATION; ANIMAL; ANTIBODY SPECIFICITY; BIOLOGY; CELL PROLIFERATION; CYTOLOGY; DNA FLANKING REGION; GENE EXPRESSION REGULATION; GENETICS; GENOME; LIVER; METABOLISM; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; PANCREAS ISLET; REGULATORY SEQUENCE;

MUS;

5' FLANKING REGION; ANIMALS; BASE SEQUENCE; CELL PROLIFERATION; COMPUTATIONAL BIOLOGY; CONSERVED SEQUENCE; GENE EXPRESSION REGULATION; GENOME; HEPATOCYTE NUCLEAR FACTOR 1-ALPHA; HEPATOCYTE NUCLEAR FACTOR 1-BETA; HEPATOCYTES; ISLETS OF LANGERHANS; LIVER; MALE; MICE; MOLECULAR SEQUENCE DATA; ORGAN SPECIFICITY; PROTEIN BINDING; REGULATORY SEQUENCES, NUCLEIC ACID; TRANSCRIPTION, GENETIC;

EID: 66349097174     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.01389-08     Document Type: Article

References (76)

1. Akiyama, T. E., J. M. Ward, and F. J. Gonzalez. 2000. Regulation of the liver fatty acid-binding protein gene by hepatocyte nuclear factor 1alpha (HNF1alpha). Alterations in fatty acid homeostasis in HNF1alpha-deficient mice. J. Biol. Chem. 275:27117-27122.
2. Akpinar, P., S. Kuwajima, J. Krutzfeldt, and M. Stoffel. 2005. Tmem27: a cleaved and shed plasma membrane protein that stimulates pancreatic beta cell proliferation. Cell Metab. 2:385-397.
3. Bluteau, O., E. Jeannot, P. Bioulac-Sage, J. M. Marques, J. F. Blanc, H. Bui, J. C. Beaudoin, D. Franco, C. Balabaud, P. Laurent-Puig, and J. Zucman-Rossi. 2002. Bi-allelic inactivation of TCF1 in hepatic adenomas. Nat. Genet. 32:312-315.
4. Boj, S. F., M. Parrizas, M. A. Maestro, and J. Ferrer. 2001. A transcription factor regulatory circuit in differentiated pancreatic cells. Proc. Natl. Acad. Sci. USA 98:14481-14486.
5. Boj, S. F., J. M. Servitja, D. Martin, I. Talianidis, R. Guigo, and J. Ferrer. Essential transcriptional functions of the monogenic diabetes regulators HNF1alpha and HNF4alpha are conserved between mice and humans. Diabetes, in press.
6. Bouatia-Naji, N., G. Rocheleau, L. Van Lommel, K. Lemaire, F. Schuit, C. Cavalcanti-Proenca, M. Marchand, A. L. Hartikainen, U. Sovio, F. De Graeve, J. Rung, M. Vaxillaire, J. Tichet, M. Marre, B. Balkau, J. Weill, P. Elliott, M. R. Jarvelin, D. Meyre, C. Polychronakos, C. Dina, R. Sladek, and P. Froguel. 2008. A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels. Science 320:1085-1088.
7. Byrne, M. M., J. Sturis, S. Menzel, K. Yamagata, S. S. Fajans, M. J. Dronsfield, S. C. Bain, A. T. Hattersley, G. Velho, P. Froguel, G. I. Bell, and K. S. Polonsky. 1996. Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome 12. Diabetes 45:1503-1510. (Pubitemid 26357541)
8. Cereghini, S. 1996. Liver-enriched transcription factors and hepatocyte differentiation. FASEB J. 10:267-282. (Pubitemid 26079946)
9. Cereghini, S., M. Blumenfeld, and M. Yaniv. 1988. A liver-specific factor essential for albumin transcription differs between differentiated and dedifferentiated rat hepatoma cells. Genes Dev. 2:957-974.
10. Cheung, C., T. E. Akiyama, G. Kudo, and F. J. Gonzalez. 2003. Hepatic expression of cytochrome P450s in hepatocyte nuclear factor 1-alpha (HNF1alpha)-deficient mice. Biochem. Pharmacol. 66:2011-2020.
11. Contreras, J. L., C. Eckstein, C. A. Smyth, G. Bilbao, M. Vilatoba, S. E. Ringland, C. Young, J. A. Thompson, J. A. Fernandez, J. H. Griffin, and D. E. Eckhoff. 2004. Activated protein C preserves functional islet mass after intraportal transplantation: a novel link between endothelial cell activation, thrombosis, inflammation, and islet cell death. Diabetes 53:2804-2814. (Pubitemid 39425905)
12. Cras-Meneur, C., H. Inoue, Y. Zhou, M. Ohsugi, E. Bernal-Mizrachi, D. Pape, S. W. Clifton, and M. A. Permutt. 2004. An expression profile of human pancreatic islet mRNAs by Serial Analysis of Gene Expression (SAGE). Diabetologia 47:284-299. (Pubitemid 38315365)
13. Dukes, I. D., S. Sreenan, M. W. Roe, M. Levisetti, Y. P. Zhou, D. Ostrega, G. I. Bell, M. Pontoglio, M. Yaniv, L. Philipson, and K. S. Polonsky. 1998. Defective pancreatic beta-cell glycolytic signaling in hepatocyte nuclear factor- 1alpha-deficient mice. J. Biol. Chem. 273:24457-24464.
14. Efrat, S., S. Linde, H. Kofod, D. Spector, M. Delannoy, S. Grant, D. Hanahan, and S. Baekkeskov. 1988. Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene. Proc. Natl. Acad. Sci. USA 85:9037-9041.
15. Ferrer, J., R. Gomis, A. J. Fernandez, R. Casamitjana, and E. Vilardell. 1993. Signals derived from glucose metabolism are required for glucose regulation of pancreatic islet GLUT2 mRNA and protein. Diabetes 42:1273-1280. (Pubitemid 23259846)
16. Frayling, T. M., J. C. Evans, M. P. Bulman, E. Pearson, L. Allen, K. Owen, C. Bingham, M. Hannemann, M. Shepherd, S. Ellard, and A. T. Hattersley. 2001. Beta-cell genes and diabetes: molecular and clinical characterization of mutations in transcription factors. Diabetes 50(Suppl. 1):S94-S100. (Pubitemid 32148228)
17. Fukui, K., Q. Yang, Y. Cao, N. Takahashi, H. Hatakeyama, H. Wang, J. Wada, Y. Zhang, L. Marselli, T. Nammo, K. Yoneda, M. Onishi, S. Higashiyama, Y. Matsuzawa, F. J. Gonzalez, G. C. Weir, H. Kasai, I. Shimomura, J. Miyagawa, C. B. Wollheim, and K. Yamagata. 2005. The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation. Cell Metab. 2:373-384.
18. Garcia-Ocana, A., R. C. Vasavada, K. K. Takane, A. Cebrian, J. C. Lopez-Talavera, and A. F. Stewart. 2001. Using beta-cell growth factors to enhance human pancreatic Islet transplantation. J. Clin. Endocrinol. Metab. 86:984-988.
19. Gresh, L., E. Fischer, A. Reimann, M. Tanguy, S. Garbay, X. Shao, T. Hiesberger, L. Fiette, P. Igarashi, M. Yaniv, and M. Pontoglio. 2004. A transcriptional network in polycystic kidney disease. EMBO J. 23:1657-1668. (Pubitemid 38579526)
20. Gudmundsson, J., P. Sulem, V. Steinthorsdottir, J. T. Bergthorsson, G. Thorleifsson, A. Manolescu, T. Rafnar, D. Gudbjartsson, B. A. Agnarsson, A. Baker, A. Sigurdsson, K. R. Benediktsdottir, M. Jakobsdottir, T. Blondal, S. N. Stacey, A. Helgason, S. Gunnarsdottir, A. Olafsdottir, K. T. Kristinsson, B. Birgisdottir, S. Ghosh, S. Thorlacius, D. Magnusdottir, G. Stefansdottir, K. Kristjansson, Y. Bagger, R. L. Wilensky, M. P. Reilly, A. D. Morris, C. H. Kimber, A. Adeyemo, Y. Chen, J. Zhou, W. Y. So, P. C. Tong, M. C. Ng, T. Hansen, G. Andersen, K. Borch-Johnsen, T. Jorgensen, A. Tres, F. Fuertes, M. Ruiz-Echarri, L. Asin, B. Saez, E. van Boven, S. Klaver, D. W. Swinkels, K. K. Aben, T. Graif, J. Cashy, B. K. Suarez, T. O. van Vierssen, M. L. Frigge, C. Ober, M. H. Hofker, C. Wijmenga, C. Christiansen, D. J. Rader, C. N. Palmer, C. Rotimi, J. C. Chan, O. Pedersen, G. Sigurdsson, R. Benediktsson, E. Jonsson, G. V. Einarsson, J. I. Mayordomo, W. J. Catalona, L. A. Kiemeney, R. B. Barkardottir, J. R. Gulcher, U. Thorsteinsdottir, A. Kong, and K. Stefansson. 2007. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat. Genet. 39:977-983.
21. Guillam, M. T., E. Hummler, E. Schaerer, J. I. Yeh, M. J. Birnbaum, F. Beermann, A. Schmidt, N. Deriaz, and B. Thorens. 1997. Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2. Nat. Genet. 17:327-330.
22. Gupta, R. K., M. Z. Vatamaniuk, C. S. Lee, R. C. Flaschen, J. T. Fulmer, F. M. Matschinsky, S. A. Duncan, and K. H. Kaestner. 2005. The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion. J. Clin. Investig. 115:1006-1015.
23. Hagenfeldt-Johansson, K. A., P. L. Herrera, H. Wang, A. Gjinovci, H. Ishihara, and C. B. Wollheim. 2001. Beta-cell-targeted expression of a dominant-negative hepatocyte nuclear factor-1 alpha induces a maturity-onset diabetes of the young (MODY)3-like phenotype in transgenic mice. Endocrinology 142:5311-5320. (Pubitemid 33131963)
24. Haumaitre, C., M. Reber, and S. Cereghini. 2003. Functions of HNF1 family members in differentiation of the visceral endoderm cell lineage. J. Biol. Chem. 278:40933-40942.
25. He, N., K. Park, Y. Zhang, J. Huang, S. Lu, and L. Wang. 2008. Epigenetic inhibition of nuclear receptor small heterodimer partner is associated with and regulates hepatocellular carcinoma growth. Gastroenterology 134:793-802.
26. Hiraiwa, H., C. J. Pan, B. Lin, T. E. Akiyama, F. J. Gonzalez, and J. Y. Chou. 2001. A molecular link between the common phenotypes of type 1 glycogen storage disease and HNF1alpha-null mice. J. Biol. Chem. 276:7963-7967.
27. Kim, I., K. Morimura, Y. Shah, Q. Yang, J. M. Ward, and F. J. Gonzalez. 2007. Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice. Carcinogenesis 28:940-946. (Pubitemid 47072176)
28. Kobayashi, H. 2006. Endogenous anti-inflammatory substances, inter-alpha-inhibitor and bikunin. Biol. Chem. 387:1545-1549.
29. Kyrmizi, I., P. Hatzis, N. Katrakili, F. Tronche, F. J. Gonzalez, and I. Talianidis. 2006. Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev. 20:2293-2305. (Pubitemid 44244529)
30. Lee, Y. H., B. Sauer, and F. J. Gonzalez. 1998. Laron dwarfism and non-insulin-dependent diabetes mellitus in the Hnf-1alpha knockout mouse. Mol. Cell. Biol. 18:3059-3068.
31. Lehto, M., T. Tuomi, M. M. Mahtani, E. Widen, C. Forsblom, L. Sarelin, M. Gullstrom, B. Isomaa, M. Lehtovirta, A. Hyrkko, T. Kanninen, M. Orho, S. Manley, R. C. Turner, T. Brettin, A. Kirby, J. Thomas, G. Duyk, E. Lander, M. R. Taskinen, and L. Groop. 1997. Characterization of the MODY3 phenotype. Early-onset diabetes caused by an insulin secretion defect. J. Clin. Investig. 99:582-591.
32. Li, X. Y., S. MacArthur, R. Bourgon, D. Nix, D. A. Pollard, V. N. Iyer, A. Hechmer, L. Simirenko, M. Stapleton, C. L. Luengo Hendriks, H. C. Chu, N. Ogawa, W. Inwood, V. Sementchenko, A. Beaton, R. Weiszmann, S. E. Celniker, D. W. Knowles, T. Gingeras, T. P. Speed, M. B. Eisen, and M. D. Biggin. 2008. Transcription factors bind thousands of active and inactive regions in the Drosophila blastoderm. PLoS Biol. 6:e27.
33. Loh, Y. H., Q. Wu, J. L. Chew, V. B. Vega, W. Zhang, X. Chen, G. Bourque, J. George, B. Leong, J. Liu, K. Y. Wong, K. W. Sung, C. W. Lee, X. D. Zhao, K. P. Chiu, L. Lipovich, V. A. Kuznetsov, P. Robson, L. W. Stanton, C. L. Wei, Y. Ruan, B. Lim, and H. H. Ng. 2006. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat. Genet. 38:431-440.
34. Luco, R. F., M. A. Maestro, N. del Pozo, W. M. Philbrick, P. P. de la Ossa, and J. Ferrer. 2006. A conditional model reveals that induction of hepatocyte nuclear factor-1alpha in Hnf1alpha-null mutant beta-cells can activate silenced genes postnatally, whereas overexpression is deleterious. Diabetes 55:2202-2211. (Pubitemid 44743616)
35. Luco, R. F., M. A. Maestro, N. Sadoni, D. Zink, and J. Ferrer. 2008. Targeted deficiency of the transcriptional activator Hnf1alpha alters subnuclear positioning of its genomic targets. PLoS Genet. 4:e1000079.
36. Maechler, P., and C. B. Wollheim. 2001. Mitochondrial function in normal and diabetic beta-cells. Nature 414:807-812. (Pubitemid 34000784)
37. Maestro, M. A., S. F. Boj, R. F. Luco, C. E. Pierreux, J. Cabedo, J. M. Servitja, M. S. German, G. G. Rousseau, F. P. Lemaigre, and J. Ferrer. 2003. Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell domain of the embryonic pancreas. Hum. Mol. Genet. 12:3307-3314.
38. Maestro, M. A., C. Cardalda, S. F. Boj, R. F. Luco, J. M. Servitja, and J. Ferrer. 2007. Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth. Endocr. Dev. 12:33-45.
39. Massa, L., S. Baltrusch, D. A. Okar, A. J. Lange, S. Lenzen, and M. Tiedge. 2004. Interaction of 6-phosphofructo-2-kinase/fructose-2,6- bisphosphatase (PFK-2/FBPase-2) with glucokinase activates glucose phosphorylation and glucose metabolism in insulin-producing cells. Diabetes 53:1020-1029. (Pubitemid 38436614)
40. Murphy, R., S. Ellard, and A. T. Hattersley. 2008. Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes. Nat. Clin. Pract. Endocrinol. Metab. 4:200-213.
41. Nammo, T., K. Yamagata, T. Tanaka, T. Kodama, F. M. Sladek, K. Fukui, F. Katsube, Y. Sato, J. Miyagawa, and I. Shimomura. 2008. Expression of HNF-4alpha (MODY1), HNF-1beta (MODY5), and HNF-1alpha (MODY3) proteins in the developing mouse pancreas. Gene Expr. Patterns 8:96-106. (Pubitemid 350278490)
42. Newsholme, P., L. Brennan, B. Rubi, and P. Maechler. 2005. New insights into amino acid metabolism, beta-cell function and diabetes. Clin. Sci. (London) 108:185-194.
43. Odom, D. T., R. D. Dowell, E. S. Jacobsen, W. Gordon, T. W. Danford, K. D. MacIsaac, P. A. Rolfe, C. M. Conboy, D. K. Gifford, and E. Fraenkel. 2007. Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat. Genet. 39:730-732.
44. Odom, D. T., N. Zizlsperger, D. B. Gordon, G. W. Bell, N. J. Rinaldi, H. L. Murray, T. L. Volkert, J. Schreiber, P. A. Rolfe, D. K. Gifford, E. Fraenkel, G. I. Bell, and R. A. Young. 2004. Control of pancreas and liver gene expression by HNF transcription factors. Science 303:1378-1381. (Pubitemid 38269432)
45. Ohsugi, M., C. Cras-Meneur, Y. Zhou, W. Warren, E. Bernal-Mizrachi, and M. A. Permutt. 2004. Glucose and insulin treatment of insulinoma cells results in transcriptional regulation of a common set of genes. Diabetes 53:1496-1508. (Pubitemid 38697662)
46. Párrizas, M., M. A. Maestro, S. F. Boj, A. Paniagua, R. Casamitjana, R. Gomis, F. Rivera, and J. Ferrer. 2001. Hepatic nuclear factor 1-alpha directs nucleosomal hyperacetylation to its tissue-specific transcriptional targets. Mol. Cell. Biol. 21:3234-3243.
47. Pearson, E. R., S. F. Boj, A. M. Steele, T. Barrett, K. Stals, J. P. Shield, S. Ellard, J. Ferrer, and A. T. Hattersley. 2007. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med. 4:e118.
48. Pearson, E. R., B. J. Starkey, R. J. Powell, F. M. Gribble, P. M. Clark, and A. T. Hattersley. 2003. Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet 362:1275-1281. (Pubitemid 37324255)
49. Pontoglio, M., J. Barra, M. Hadchouel, A. Doyen, C. Kress, J. P. Bach, C. Babinet, and M. Yaniv. 1996. Hepatocyte nuclear factor 1 inactivation results in hepatic dysfunction, phenylketonuria, and renal Fanconi syndrome. Cell 84:575-585. (Pubitemid 26071738)
50. Pontoglio, M., S. Sreenan, M. Roe, W. Pugh, D. Ostrega, A. Doyen, A. J. Pick, A. Baldwin, G. Velho, P. Froguel, M. Levisetti, S. Bonner-Weir, G. I. Bell, M. Yaniv, and K. S. Polonsky. 1998. Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice. J. Clin. Investig. 101:2215-2222.
51. Rajas, F., H. Jourdan-Pineau, A. Stefanutti, E. A. Mrad, P. B. Iynedjian, and G. Mithieux. 2007. Immunocytochemical localization of glucose 6-phosphatase and cytosolic phosphoenolpyruvate carboxykinase in gluconeogenic tissues reveals unsuspected metabolic zonation. Histochem. Cell Biol. 127:555-565.
52. Refai, E., N. Dekki, S. N. Yang, G. Imreh, O. Cabrera, L. Yu, G. Yang, S. Norgren, S. M. Rossner, L. Inverardi, C. Ricordi, G. Olivecrona, M. Andersson, H. Jornvall, P. O. Berggren, and L. Juntti-Berggren. 2005. Transthyretin constitutes a functional component in pancreatic beta-cell stimulus-secretion coupling. Proc. Natl. Acad. Sci. USA 102:17020-17025.
53. Rodolosse, A., V. Carriere, M. Rousset, and M. Lacasa. 1998. Two HNF-1 binding sites govern the glucose repression of the human sucrase-isomaltase promoter. Biochem. J. 336:115-123. (Pubitemid 28532568)
54. Roehrich, M. E., V. Mooser, V. Lenain, J. Herz, J. Nimpf, S. Azhar, M. Bideau, A. Capponi, P. Nicod, J. A. Haefliger, and G. Waeber. 2003. Insulin-secreting beta-cell dysfunction induced by human lipoproteins. J. Biol. Chem. 278:18368-18375.
55. Rubi, B., S. Ljubicic, S. Pournourmohammadi, S. Carobbio, M. Armanet, C. Bartley, and P. Maechler. 2005. Dopamine D2-like receptors are expressed in pancreatic beta cells and mediate inhibition of insulin secretion. J. Biol. Chem. 280:36824-36832.
56. Rukstalis, J. M., and J. F. Habener. 2007. Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor cells of the developing endocrine pancreas. Gene Expr. Patterns 7:471-479. (Pubitemid 46172933)
57. Schuit, F., D. Flamez, A. De Vos, and D. Pipeleers. 2002. Glucose-regulated gene expression maintaining the glucose-responsive state of beta-cells. Diabetes 51(Suppl. 3):S326-S332. (Pubitemid 35403412)
58. Servitja, J. M., and J. Ferrer. 2004. Transcriptional networks controlling pancreatic development and beta cell function. Diabetologia 47:597-613. (Pubitemid 38658361)
59. Shih, D. Q., M. Bussen, E. Sehayek, M. Ananthanarayanan, B. L. Shneider, F. J. Suchy, S. Shefer, J. S. Bollileni, F. J. Gonzalez, J. L. Breslow, and M. Stoffel. 2001. Hepatocyte nuclear factor-1alpha is an essential regulator of bile acid and plasma cholesterol metabolism. Nat. Genet. 27:375-382.
60. Shih, D. Q., S. Screenan, K. N. Munoz, L. Philipson, M. Pontoglio, M. Yaniv, K. S. Polonsky, and M. Stoffel. 2001. Loss of HNF-1alpha function in mice leads to abnormal expression of genes involved in pancreatic islet development and metabolism. Diabetes 50:2472-2480. (Pubitemid 33642764)
61. Streeper, R. S., E. M. Eaton, D. H. Ebert, S. C. Chapman, C. A. Svitek, and R. M. O'Brien. 1998. Hepatocyte nuclear factor-1 acts as an accessory factor to enhance the inhibitory action of insulin on mouse glucose-6-phosphatase gene transcription. Proc. Natl. Acad. Sci. USA 95:9208-9213.
62. Terauchi, Y., I. Takamoto, N. Kubota, J. Matsui, R. Suzuki, K. Komeda, A. Hara, Y. Toyoda, I. Miwa, S. Aizawa, S. Tsutsumi, Y. Tsubamoto, S. Hashimoto, K. Eto, A. Nakamura, M. Noda, K. Tobe, H. Aburatani, R. Nagai, and T. Kadowaki. 2007. Glucokinase and IRS-2 are required for compensatory beta cell hyperplasia in response to high-fat diet-induced insulin resistance. J. Clin. Investig. 117:246-257.
63. Tronche, F., F. Ringeisen, M. Blumenfeld, M. Yaniv, and M. Pontoglio. 1997. Analysis of the distribution of binding sites for a tissue-specific transcription factor in the vertebrate genome. J. Mol. Biol. 266:231-245.
64. Vasavada, R. C., J. A. Gonzalez-Pertusa, Y. Fujinaka, N. Fiaschi-Taesch, I. Cozar-Castellano, and A. Garcia-Ocana. 2006. Growth factors and beta cell replication. Int. J. Biochem. Cell Biol. 38:931-950.
65. Vaxillaire, M., V. Boccio, A. Philippi, C. Vigouroux, J. Terwilliger, P. Passa, J. S. Beckmann, G. Velho, G. M. Lathrop, and P. Froguel. 1995. A gene for maturity onset diabetes of the young (MODY) maps to chromosome 12q. Nat. Genet. 9:418-423.
66. Wang, H., P. A. Antinozzi, K. A. Hagenfeldt, P. Maechler, and C. B. Wollheim. 2000. Molecular targets of a human HNF1 alpha mutation responsible for pancreatic beta-cell dysfunction. EMBO J. 19:4257-4264. (Pubitemid 30623736)
67. Wang, H., P. Maechler, K. A. Hagenfeldt, and C. B. Wollheim. 1998. Dominant- negative suppression of HNF-1alpha function results in defective insulin gene transcription and impaired metabolism-secretion coupling in a pancreatic beta-cell line. EMBO J. 17:6701-6713. (Pubitemid 28521803)
68. Wang, H., and C. B. Wollheim. 2002. ChREBP rather than USF2 regulates glucose stimulation of endogenous L-pyruvate kinase expression in insulin-secreting cells. J. Biol. Chem. 277:32746-32752.
69. Westermark, P. O., and A. Lansner. 2003. A model of phosphofructokinase and glycolytic oscillations in the pancreatic beta-cell. Biophys. J. 85:126-139. (Pubitemid 36753622)
70. Wilson, M. E., D. Scheel, and M. S. German. 2003. Gene expression cascades in pancreatic development. Mech. Dev. 120:65-80.
71. Yamagata, K., H. Furuta, N. Oda, P. J. Kaisaki, S. Menzel, N. J. Cox, S. S. Fajans, S. Signorini, M. Stoffel, and G. I. Bell. 1996. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature 384:458-460. (Pubitemid 26414661)
72. Yamagata, K., T. Nammo, M. Moriwaki, A. Ihara, K. Iizuka, Q. Yang, T. Satoh, M. Li, R. Uenaka, K. Okita, H. Iwahashi, Q. Zhu, Y. Cao, A. Imagawa, Y. Tochino, T. Hanafusa, J. Miyagawa, and Y. Matsuzawa. 2002. Overexpression of dominant-negative mutant hepatocyte nuclear fctor-1 alpha in pancreatic beta-cells causes abnormal islet architecture with decreased expression of E-cadherin, reduced beta-cell proliferation, and diabetes. Diabetes 51:114-123. (Pubitemid 34517987)
73. Yamagata, K., N. Oda, P. J. Kaisaki, S. Menzel, H. Furuta, M. Vaxillaire, L. Southam, R. D. Cox, G. M. Lathrop, V. V. Boriraj, X. Chen, N. J. Cox, Y. Oda, H. Yano, M. M. Le Beau, S. Yamada, H. Nishigori, J. Takeda, S. S. Fajans, A. T. Hattersley, N. Iwasaki, T. Hansen, O. Pedersen, K. S. Polonsky, G. I. Bell, et al. 1996. Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). Nature 384:455-458. (Pubitemid 26414660)
74. Yang, A., Z. Zhu, P. Kapranov, F. McKeon, G. M. Church, T. R. Gingeras, and K. Struhl. 2006. Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells. Mol. Cell 24:593-602. (Pubitemid 350284225)
75. Yang, F., X. Huang, T. Yi, Y. Yen, D. D. Moore, and W. Huang. 2007. Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. Cancer Res. 67:863-867. (Pubitemid 46270737)
76. Zeggini, E., L. J. Scott, R. Saxena, B. F. Voight, J. L. Marchini, T. Hu, P. I. de Bakker, G. R. Abecasis, P. Almgren, G. Andersen, K. Ardlie, K. B. Bostrom, R. N. Bergman, L. L. Bonnycastle, K. Borch-Johnsen, N. P. Burtt, H. Chen, P. S. Chines, M. J. Daly, P. Deodhar, C. J. Ding, A. S. Doney, W. L. Duren, K. S. Elliott, M. R. Erdos, T. M. Frayling, R. M. Freathy, L. Gianniny, H. Grallert, N. Grarup, C. J. Groves, C. Guiducci, T. Hansen, C. Herder, G. A. Hitman, T. E. Hughes, B. Isomaa, A. U. Jackson, T. Jorgensen, A. Kong, K. Kubalanza, F. G. Kuruvilla, J. Kuusisto, C. Langenberg, H. Lango, T. Lauritzen, Y. Li, C. M. Lindgren, V. Lyssenko, A. F. Marvelle, C. Meisinger, K. Midthjell, K. L. Mohlke, M. A. Morken, A. D. Morris, N. Narisu, P. Nilsson, K. R. Owen, C. N. Palmer, F. Payne, J. R. Perry, E. Pettersen, C. Platou, I. Prokopenko, L. Qi, L. Qin, N. W. Rayner, M. Rees, J. J. Roix, A. Sandbaek, B. Shields, M. Sjogren, V. Steinthorsdottir, H. M. Stringham, A. J. Swift, G. Thorleifsson, U. Thorsteinsdottir, N. J. Timpson, T. Tuomi, J. Tuomilehto, M. Walker, R. M. Watanabe, M. N. Weedon, C. J. Willer, T. Illig, K. Hveem, F. B. Hu, M. Laakso, K. Stefansson, O. Pedersen, N. J. Wareham, I. Barroso, A. T. Hattersley, F. S. Collins, L. Groop, M. I. McCarthy, M. Boehnke, and D. Altshuler. 2008. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat. Genet. 40:638-645.