Molecular Endocrinology, Vol 8, 1798-1806, Copyright © 1994 by Endocrine Society

ARTICLES

Insulin expression in pancreatic islet cells relies on cooperative interactions between the helix loop helix factor E47 and the homeobox factor STF-1

B Peers, J Leonard, S Sharma, G Teitelman and MR Montminy
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.

The development of endocrine cell types within the pancreas is thought to involve the progressive restriction of pluripotential stem cells, which gives rise to the four major cell types: insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-expressing cells. The mechanism by which these peptide hormone genes are induced and then either maintained or repressed during development is unknown, but their coexpression in early precursor cells suggests the involvement of common regulatory factors. Here we show that the somatostatin transcription factor STF-1 is also a principal regulator of insulin expression in beta-cells of the pancreas. STF-1 stimulates the insulin gene by recognizing two well defined islet-specifying elements on the insulin promoter and by subsequently synergizing in trans with the juxtaposed helix-loop-helix protein E47. Within the STF-1 protein, an N- terminal trans-activation domain functions cooperatively with E47 to stimulate insulin transcription. As truncated STF-1 polypeptides lacking the N-terminal activation domain strongly inhibit insulin promoter activity in beta-islet cells, our results suggest that the specification of islet cell types during development may be in part determined by the expression of STF-1 relative to other islet cell factors.

This article has been cited by other articles:

				M.-J. Boucher, M. Simoneau, and H. Edlund The Homeodomain-Interacting Protein Kinase 2 Regulates Insulin Promoter Factor-1/Pancreatic Duodenal Homeobox-1 Transcriptional Activity Endocrinology, January 1, 2009; 150(1): 87 - 97. [Abstract] [Full Text] [PDF]

				F. Diraison, M. A. Ravier, S. K. Richards, R. M. Smith, H. Shimano, and G. A. Rutter SREBP1 is required for the induction by glucose of pancreatic {beta}-cell genes involved in glucose sensing J. Lipid Res., April 1, 2008; 49(4): 814 - 822. [Abstract] [Full Text] [PDF]

				T.-a. Matsuoka, H. Kaneto, R. Stein, T. Miyatsuka, D. Kawamori, E. Henderson, I. Kojima, M. Matsuhisa, M. Hori, and Y. Yamasaki MafA Regulates Expression of Genes Important to Islet {beta}-Cell Function Mol. Endocrinol., November 1, 2007; 21(11): 2764 - 2774. [Abstract] [Full Text] [PDF]

				P. Newsholme, E. P. Haber, S. M. Hirabara, E. L. O. Rebelato, J. Procopio, D. Morgan, H. C. Oliveira-Emilio, A. R. Carpinelli, and R. Curi Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity J. Physiol., August 15, 2007; 583(1): 9 - 24. [Abstract] [Full Text] [PDF]

				J. Gromada, I. Franklin, and C. B. Wollheim {alpha}-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains Endocr. Rev., February 1, 2007; 28(1): 84 - 116. [Abstract] [Full Text] [PDF]

				T. B. Deramaudt, M. M. Sachdeva, M. P. Wescott, Y. Chen, D. A. Stoffers, and A. K. Rustgi The PDX1 Homeodomain Transcription Factor Negatively Regulates the Pancreatic Ductal Cell-specific Keratin 19 Promoter J. Biol. Chem., December 15, 2006; 281(50): 38385 - 38395. [Abstract] [Full Text] [PDF]

				C. W. Hay and K. Docherty Comparative Analysis of Insulin Gene Promoters: Implications for Diabetes Research Diabetes, December 1, 2006; 55(12): 3201 - 3213. [Abstract] [Full Text] [PDF]

				M. Mirasierra and M. Vallejo The Homeoprotein Alx3 Expressed in Pancreatic ss-Cells Regulates Insulin Gene Transcription by Interacting with the Basic Helix-Loop-Helix Protein E47 Mol. Endocrinol., November 1, 2006; 20(11): 2876 - 2889. [Abstract] [Full Text] [PDF]

				S. Ge, G. M. Crooks, G. McNamara, and X. Wang Fluorescent Immunohistochemistry and In Situ Hybridization Analysis of Mouse Pancreas Using Low-power Antigen-retrieval Technique J. Histochem. Cytochem., July 1, 2006; 54(7): 843 - 847. [Abstract] [Full Text] [PDF]

				K. Eto, V. Kaur, and M. K. Thomas Regulation of Insulin Gene Transcription by the Immediate-Early Growth Response Gene Egr-1 Endocrinology, June 1, 2006; 147(6): 2923 - 2935. [Abstract] [Full Text] [PDF]

				V. Poitout, D. Hagman, R. Stein, I. Artner, R. P. Robertson, and J. S. Harmon Regulation of the Insulin Gene by Glucose and Fatty Acids J. Nutr., April 1, 2006; 136(4): 873 - 876. [Abstract] [Full Text] [PDF]

				J. Le Lay and R. Stein Involvement of PDX-1 in activation of human insulin gene transcription J. Endocrinol., February 1, 2006; 188(2): 287 - 294. [Abstract] [Full Text] [PDF]

				P. Lebrun, M. R. Montminy, and E. Van Obberghen Regulation of the Pancreatic Duodenal Homeobox-1 Protein by DNA-dependent Protein Kinase J. Biol. Chem., November 18, 2005; 280(46): 38203 - 38210. [Abstract] [Full Text] [PDF]

				H. Iguchi, Y. Ikeda, M. Okamura, T. Tanaka, Y. Urashima, H. Ohguchi, S. Takayasu, N. Kojima, S. Iwasaki, R. Ohashi, et al. SOX6 Attenuates Glucose-stimulated Insulin Secretion by Repressing PDX1 Transcriptional Actvity and Is Down-regulated in Hyperinsulinemic Obese Mice J. Biol. Chem., November 11, 2005; 280(45): 37669 - 37680. [Abstract] [Full Text] [PDF]

				M. C. Lawrence, K. McGlynn, B.-H. Park, and M. H. Cobb ERK1/2-dependent Activation of Transcription Factors Required for Acute and Chronic Effects of Glucose on the Insulin Gene Promoter J. Biol. Chem., July 22, 2005; 280(29): 26751 - 26759. [Abstract] [Full Text] [PDF]

				H. Kaneto, Y. Nakatani, T. Miyatsuka, T.-a. Matsuoka, M. Matsuhisa, M. Hori, and Y. Yamasaki PDX-1/VP16 Fusion Protein, Together With NeuroD or Ngn3, Markedly Induces Insulin Gene Transcription and Ameliorates Glucose Tolerance Diabetes, April 1, 2005; 54(4): 1009 - 1022. [Abstract] [Full Text] [PDF]

				G. Flock, X. Cao, and D. J. Drucker Pdx-1 Is Not Sufficient for Repression of Proglucagon Gene Transcription in Islet or Enteroendocrine Cells Endocrinology, January 1, 2005; 146(1): 441 - 449. [Abstract] [Full Text] [PDF]

				L. I. Jepeal, Y. Fujitani, M. O. Boylan, C. N. Wilson, C. V. Wright, and M. M. Wolfe Cell-Specific Expression of Glucose-Dependent-Insulinotropic Polypeptide Is Regulated by the Transcription Factor PDX-1 Endocrinology, January 1, 2005; 146(1): 383 - 391. [Abstract] [Full Text] [PDF]

				V. Stanojevic, J. F. Habener, and M. K. Thomas Pancreas Duodenum Homeobox-1 Transcriptional Activation Requires Interactions with p300 Endocrinology, June 1, 2004; 145(6): 2918 - 2928. [Abstract] [Full Text] [PDF]

				A. Liu, B. M. Desai, and D. A. Stoffers Identification of PCIF1, a POZ Domain Protein That Inhibits PDX-1 (MODY4) Transcriptional Activity Mol. Cell. Biol., May 15, 2004; 24(10): 4372 - 4383. [Abstract] [Full Text] [PDF]

				S.-H. Chao, J. N. Harada, F. Hyndman, X. Gao, C. G. Nelson, S. K. Chanda, and J. S. Caldwell PDX1, a Cellular Homeoprotein, Binds to and Regulates the Activity of Human Cytomegalovirus Immediate Early Promoter J. Biol. Chem., April 16, 2004; 279(16): 16111 - 16120. [Abstract] [Full Text] [PDF]

				B. N. Cockburn, G. Bermano, L.-L. G. Boodram, S. Teelucksingh, T. Tsuchiya, D. Mahabir, A. B. Allan, R. Stein, K. Docherty, and G. I. Bell Insulin Promoter Factor-1 Mutations and Diabetes in Trinidad: Identification of a Novel Diabetes-Associated Mutation (E224K) in an Indo-Trinidadian Family J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 971 - 978. [Abstract] [Full Text] [PDF]

				R. Suzuki, K. Tobe, Y. Terauchi, K. Komeda, N. Kubota, K. Eto, T. Yamauchi, K. Azuma, H. Kaneto, T. Taguchi, et al. Pdx1 Expression in Irs2-deficient Mouse {beta}-Cells Is Regulated in a Strain-dependent Manner J. Biol. Chem., October 31, 2003; 278(44): 43691 - 43698. [Abstract] [Full Text] [PDF]

				V. M. Schwitzgebel, A. Mamin, T. Brun, B. Ritz-Laser, M. Zaiko, A. Maret, F. R. Jornayvaz, G. E. Theintz, O. Michielin, D. Melloul, et al. Agenesis of Human Pancreas due to Decreased Half-Life of Insulin Promoter Factor 1 J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4398 - 4406. [Abstract] [Full Text] [PDF]

				T.-a. Matsuoka, L. Zhao, I. Artner, H. W. Jarrett, D. Friedman, A. Means, and R. Stein Members of the Large Maf Transcription Family Regulate Insulin Gene Transcription in Islet {beta} Cells Mol. Cell. Biol., September 1, 2003; 23(17): 6049 - 6062. [Abstract] [Full Text] [PDF]

				S. Khoo, S. C. Griffen, Y. Xia, R. J. Baer, M. S. German, and M. H. Cobb Regulation of Insulin Gene Transcription by ERK1 and ERK2 in Pancreatic {beta} Cells J. Biol. Chem., August 29, 2003; 278(35): 32969 - 32977. [Abstract] [Full Text] [PDF]

				K. Kataoka, S.-i. Han, S. Shioda, M. Hirai, M. Nishizawa, and H. Handa MafA Is a Glucose-regulated and Pancreatic beta -Cell-specific Transcriptional Activator for the Insulin Gene J. Biol. Chem., December 13, 2002; 277(51): 49903 - 49910. [Abstract] [Full Text] [PDF]

				D. Melloul, S. Marshak, and E. Cerasi Regulation of pdx-1 Gene Expression Diabetes, December 1, 2002; 51(90003): S320 - 325. [Abstract] [Full Text] [PDF]

				R. Bartoov-Shifman, R. Hertz, H. Wang, C. B. Wollheim, J. Bar-Tana, and M. D. Walker Activation of the Insulin Gene Promoter through a Direct Effect of Hepatocyte Nuclear Factor 4alpha J. Biol. Chem., July 12, 2002; 277(29): 25914 - 25919. [Abstract] [Full Text] [PDF]

				S. K. Chakrabarti, J. C. James, and R. G. Mirmira Quantitative Assessment of Gene Targeting in Vitro and in Vivo by the Pancreatic Transcription Factor, Pdx1. IMPORTANCE OF CHROMATIN STRUCTURE IN DIRECTING PROMOTER BINDING J. Biol. Chem., April 5, 2002; 277(15): 13286 - 13293. [Abstract] [Full Text] [PDF]

				M. Brissova, M. Shiota, W. E. Nicholson, M. Gannon, S. M. Knobel, D. W. Piston, C. V. E. Wright, and A. C. Powers Reduction in Pancreatic Transcription Factor PDX-1 Impairs Glucose-stimulated Insulin Secretion J. Biol. Chem., March 22, 2002; 277(13): 11225 - 11232. [Abstract] [Full Text] [PDF]

				Y. Qiu, M. Guo, S. Huang, and R. Stein Insulin Gene Transcription Is Mediated by Interactions between the p300 Coactivator and PDX-1, BETA2, and E47 Mol. Cell. Biol., January 15, 2002; 22(2): 412 - 420. [Abstract] [Full Text] [PDF]

				K. Gerrish, M. A. Cissell, and R. Stein The Role of Hepatic Nuclear Factor 1alpha and PDX-1 in Transcriptional Regulation of the pdx-1 Gene J. Biol. Chem., December 14, 2001; 276(51): 47775 - 47784. [Abstract] [Full Text] [PDF]

				J. J. Tremblay and R. S. Viger GATA Factors Differentially Activate Multiple Gonadal Promoters through Conserved GATA Regulatory Elements Endocrinology, March 1, 2001; 142(3): 977 - 986. [Abstract] [Full Text] [PDF]

				M. K. Thomas, J. H. Lee, N. Rastalsky, and J. F. Habener Hedgehog Signaling Regulation of Homeodomain Protein Islet Duodenum Homeobox-1 Expression in Pancreatic {{beta}}-Cells Endocrinology, March 1, 2001; 142(3): 1033 - 1040. [Abstract] [Full Text] [PDF]

				S. Dutta, M. Gannon, B. Peers, C. Wright, S. Bonner-Weir, and M. Montminy PDX:PBX complexes are required for normal proliferation of pancreatic cells during development PNAS, January 10, 2001; (2001) 31561298. [Abstract] [Full Text]

				S. C. Griffen, J. Wang, and M. S. German A Genetic Defect in {beta}-Cell Gene Expression Segregates Independently From the fa Locus in the ZDF Rat Diabetes, January 1, 2001; 50(1): 63 - 68. [Abstract] [Full Text]

				M. Peshavaria, M. A. Cissell, E. Henderson, H. V. Petersen, and R. Stein The PDX-1 Activation Domain Provides Specific Functions Necessary for Transcriptional Stimulation in Pancreatic {beta}-Cells Mol. Endocrinol., December 1, 2000; 14(12): 1907 - 1917. [Abstract] [Full Text]

				S. Marshak, E. Benshushan, M. Shoshkes, L. Havin, E. Cerasi, and D. Melloul Functional Conservation of Regulatory Elements in the pdx-1 Gene: PDX-1 and Hepatocyte Nuclear Factor 3beta Transcription Factors Mediate beta -Cell-Specific Expression Mol. Cell. Biol., October 15, 2000; 20(20): 7583 - 7590. [Abstract] [Full Text]

				G. Poulin, M. Lebel, M. Chamberland, F. W. Paradis, and J. Drouin Specific Protein-Protein Interaction between Basic Helix-Loop-Helix Transcription Factors and Homeoproteins of the Pitx Family Mol. Cell. Biol., July 1, 2000; 20(13): 4826 - 4837. [Abstract] [Full Text]

				P. Itkin-Ansari, C. Demeterco, S. Bossie, D. Dufayet de la Tour, G. M. Beattie, J. Movassat, M. I. Mally, A. Hayek, and F. Levine PDX-1 and Cell-Cell Contact Act in Synergy to Promote {delta}-Cell Development in a Human Pancreatic Endocrine Precursor Cell Line Mol. Endocrinol., June 1, 2000; 14(6): 814 - 822. [Abstract] [Full Text]

				R. G. Mirmira, H. Watada, and M. S. German beta -Cell Differentiation Factor Nkx6.1 Contains Distinct DNA Binding Interference and Transcriptional Repression Domains J. Biol. Chem., May 5, 2000; 275(19): 14743 - 14751. [Abstract] [Full Text] [PDF]

				K. Gerrish, M. Gannon, D. Shih, E. Henderson, M. Stoffel, C. V. E. Wright, and R. Stein Pancreatic beta Cell-specific Transcription of the pdx-1 Gene. THE ROLE OF CONSERVED UPSTREAM CONTROL REGIONS AND THEIR HEPATIC NUCLEAR FACTOR 3beta SITES J. Biol. Chem., February 4, 2000; 275(5): 3485 - 3492. [Abstract] [Full Text] [PDF]

				K. Ohneda, R. G. Mirmira, J. Wang, J. D. Johnson, and M. S. German The Homeodomain of PDX-1 Mediates Multiple Protein-Protein Interactions in the Formation of a Transcriptional Activation Complex on the Insulin Promoter Mol. Cell. Biol., February 1, 2000; 20(3): 900 - 911. [Abstract] [Full Text]

				E. Glick, D. Leshkowitz, and M. D. Walker Transcription Factor BETA2 Acts Cooperatively with E2A and PDX1 to Activate the Insulin Gene Promoter J. Biol. Chem., January 21, 2000; 275(3): 2199 - 2204. [Abstract] [Full Text] [PDF]

				M. K. Thomas, K.-M. Yao, M. S. Tenser, G. G. Wong, and J. F. Habener Bridge-1, a Novel PDZ-Domain Coactivator of E2A-Mediated Regulation of Insulin Gene Transcription Mol. Cell. Biol., December 1, 1999; 19(12): 8492 - 8504. [Abstract] [Full Text] [PDF]

				D. A. Stoffers, R. S. Heller, C. P. Miller, and J. F. Habener Developmental Expression of the Homeodomain Protein IDX-1 in Mice Transgenic for an IDX-1 Promoter/lacZ Transcriptional Reporter Endocrinology, November 1, 1999; 140(11): 5374 - 5381. [Abstract] [Full Text]

				S. Beimesche, A. Neubauer, S. Herzig, R. Grzeskowiak, T. Diedrich, I. Cierny, D. Scholz, T. Alejel, and W. Knepel Tissue-Specific Transcriptional Activity of a Pancreatic Islet Cell-Specific Enhancer Sequence/Pax6-Binding Site Determined in Normal Adult Tissues in Vivo Using Transgenic Mice Mol. Endocrinol., May 1, 1999; 13(5): 718 - 728. [Abstract] [Full Text]

				G. Goudet, S. Delhalle, F. Biemar, J. A. Martial, and B. Peers Functional and Cooperative Interactions between the Homeodomain PDX1, Pbx, and Prep1 Factors on the Somatostatin Promoter J. Biol. Chem., February 12, 1999; 274(7): 4067 - 4073. [Abstract] [Full Text] [PDF]

				W. M. Macfarlane, C. M. McKinnon, Z. A. Felton-Edkins, H. Cragg, R. F. L. James, and K. Docherty Glucose Stimulates Translocation of the Homeodomain Transcription Factor PDX1 from the Cytoplasm to the Nucleus in Pancreatic beta -Cells J. Biol. Chem., January 8, 1999; 274(2): 1011 - 1016. [Abstract] [Full Text] [PDF]

				K. Kas, M. L. Voz, K. Hensen, E. Meyen, and W. J. M. Van de Ven Transcriptional Activation Capacity of the Novel PLAG Family of Zinc Finger Proteins J. Biol. Chem., September 4, 1998; 273(36): 23026 - 23032. [Abstract] [Full Text] [PDF]

				T. L. Jetton, J. M. Moates, J. Lindner, C. V. E. Wright, and M. A. Magnuson Targeted oncogenesis of hormone-negative pancreatic islet progenitor cells PNAS, July 21, 1998; 95(15): 8654 - 8659. [Abstract] [Full Text] [PDF]

				A. Øster, J. Jensen, P. Serup, P. Galante, O. D. Madsen, and L.-I. Larsson Rat Endocrine Pancreatic Development in Relation to Two Homeobox Gene Products (Pdx-1 and Nkx 6.1) J. Histochem. Cytochem., June 1, 1998; 46(6): 707 - 716. [Abstract] [Full Text]

				A. Øster, J. Jensen, H. Edlund, and L.-I. Larsson Homeobox Gene Product Nkx 6.1 Immunoreactivity in Nuclei of Endocrine Cells of Rat and Mouse Stomach J. Histochem. Cytochem., June 1, 1998; 46(6): 717 - 722. [Abstract] [Full Text]

				Y. Qiu, A. Sharma, and R. Stein p300 Mediates Transcriptional Stimulation by the Basic Helix-Loop-Helix Activators of the Insulin Gene Mol. Cell. Biol., May 1, 1998; 18(5): 2957 - 2964. [Abstract] [Full Text]

				W. M. Milewski, S. J. Duguay, S. J. Chan, and D. F. Steiner Conservation of PDX-1 Structure, Function, and Expression in Zebrafish Endocrinology, March 1, 1998; 139(3): 1440 - 1449. [Abstract] [Full Text] [PDF]

				L. K. Olson, J. Qian, and V. Poitout Glucose Rapidly and Reversibly Decreases INS-1 Cell Insulin Gene Transcription via Decrements in STF-1 and C1 Activator Transcription Factor Activity Mol. Endocrinol., February 1, 1998; 12(2): 207 - 219. [Abstract] [Full Text]

				S. Gremlich, C. Bonny, G. Waeber, and B. Thorens Fatty Acids Decrease IDX-1 Expression in Rat Pancreatic Islets and Reduce GLUT2, Glucokinase, Insulin, and Somatostatin Levels J. Biol. Chem., November 28, 1997; 272(48): 30261 - 30269. [Abstract] [Full Text] [PDF]

				H. Kaneto, J.-i. Miyagawa, Y. Kajimoto, K. Yamamoto, H. Watada, Y. Umayahara, T. Hanafusa, Y. Matsuzawa, Y. Yamasaki, S. Higashiyama, et al. Expression of Heparin-binding Epidermal Growth Factor-like Growth Factor during Pancreas Development. A POTENTIAL ROLE OF PDX-1 IN TRANSCRIPTIONAL ACTIVATION J. Biol. Chem., November 14, 1997; 272(46): 29137 - 29143. [Abstract] [Full Text] [PDF]

				M. Lu, J. Seufert, and J. F. Habener Pancreatic beta -Cell-specific Repression of Insulin Gene Transcription by CCAAT/Enhancer-binding Protein beta . INHIBITORY INTERACTIONS WITH BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTOR E47 J. Biol. Chem., November 7, 1997; 272(45): 28349 - 28359. [Abstract] [Full Text] [PDF]

				A. Sharma, E. Henderson, L. Gamer, Y. Zhuang, and R. Stein Analysis of the Role of E2A-Encoded Proteins in Insulin Gene Transcription Mol. Endocrinol., October 1, 1997; 11(11): 1608 - 1617. [Abstract] [Full Text]

				D. Mitanchez, B. Doiron, R. Chen, and A. Kahn Glucose-Stimulated Genes and Prospects of Gene Therapy for Type I Diabetes Endocr. Rev., August 1, 1997; 18(4): 520 - 540. [Abstract] [Full Text] [PDF]

				T. M. Lanigan and A. F. Russo Binding of Upstream Stimulatory Factor and a Cell-specific Activator to the Calcitonin/Calcitonin Gene-related Peptide Enhancer J. Biol. Chem., July 18, 1997; 272(29): 18316 - 18324. [Abstract] [Full Text] [PDF]

				M Sander, A Neubuser, J Kalamaras, H C Ee, G R Martin, and M S German Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development. Genes & Dev., July 1, 1997; 11(13): 1662 - 1673. [Abstract] [PDF]

				S. Marshak, H. Totary, E. Cerasi, and D. Melloul Purification of the beta -cell glucose-sensitive factor that transactivates the insulin gene differentially in normal and transformed islet cells PNAS, December 24, 1996; 93(26): 15057 - 15062. [Abstract] [Full Text] [PDF]

				J. Jensen, P. Serup, C. Karlsen, T. F. Nielsen, and O. D. Madsen mRNA Profiling of Rat Islet Tumors Reveals Nkx 6.1as a beta -Cell-specific Homeodomain Transcription Factor J. Biol. Chem., August 2, 1996; 271(31): 18749 - 18758. [Abstract] [Full Text] [PDF]

				S. Sharma, J. Leonard, S. Lee, H. D. Chapman, E. H. Leiter, and M. R. Montminy Pancreatic Islet Expression of the Homeobox Factor STF-1 Relies on an E-box Motif That Binds USF J. Biol. Chem., January 26, 1996; 271(4): 2294 - 2299. [Abstract] [Full Text] [PDF]

				M. Offield, T. Jetton, P. Labosky, M Ray, R. Stein, M. Magnuson, B. Hogan, and C. Wright PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum Development, January 3, 1996; 122(3): 983 - 995. [Abstract] [PDF]

				S. B. Smith, H. Watada, D. W. Scheel, C. Mrejen, and M. S. German Autoregulation and Maturity Onset Diabetes of the Young Transcription Factors Control the Human PAX4 Promoter J. Biol. Chem., November 17, 2000; 275(47): 36910 - 36919. [Abstract] [Full Text] [PDF]

				M. R. Dusing, E. A. Florence, and D. A. Wiginton PDX-1 Is Required for Activation in Vivo from a Duodenum-specific Enhancer J. Biol. Chem., April 20, 2001; 276(17): 14434 - 14442. [Abstract] [Full Text] [PDF]

				Y. Liu, R. J. MacDonald, and G. H. Swift DNA Binding and Transcriptional Activation by a PDX1{middle dot}PBX1b{middle dot}MEIS2b Trimer and Cooperation with a Pancreas-specific Basic Helix-Loop-Helix Complex J. Biol. Chem., May 18, 2001; 276(21): 17985 - 17993. [Abstract] [Full Text] [PDF]

				H. Wang, P. Maechler, B. Ritz-Laser, K. A. Hagenfeldt, H. Ishihara, J. Philippe, and C. B. Wollheim Pdx1 Level Defines Pancreatic Gene Expression Pattern and Cell Lineage Differentiation J. Biol. Chem., June 29, 2001; 276(27): 25279 - 25286. [Abstract] [Full Text] [PDF]

				S. Dutta, M. Gannon, B. Peers, C. Wright, S. Bonner-Weir, and M. Montminy PDX:PBX complexes are required for normal proliferation of pancreatic cells during development PNAS, January 30, 2001; 98(3): 1065 - 1070. [Abstract] [Full Text] [PDF]