| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 2, 2003
Accepted on May 19, 2004
Department of Molecular & Cellular Biochemistry (A.L.M, S.Ö.), Chandler Medical Center, University of Kentucky, 800 Rose Street, Lexington, Kentucky.; Edward A. Doisy Department of Biochemistry and Molecular Biology (J.A.C.), Saint Louis University, School of Medicine, St. Louis, Missouri
* To whom correspondence should be addressed. E-mail: sozcan{at}uky.edu.
Regulation of insulin gene expression in response to increases in blood glucose levels is essential for maintaining normal glucose homeostasis, however the exact mechanisms by which glucose stimulates insulin gene transcription are not known. We have previously shown that glucose stimulates insulin gene expression by causing the hyperacetylation of histone H4 at the insulin promoter. We demonstrate that the histone acetyltransferase p300 is recruited to the insulin promoter only at high concentrations of glucose via its interaction with the beta-cell specific transcription factor Pdx-1. Disruption of the function of the endogenous Pdx-1 abolishes the recruitment of p300 to the insulin gene promoter at high concentrations of glucose and results in decreased histone H4 acetylation and insulin gene expression. Furthermore, we demonstrate that the glucose-dependent interaction of Pdx-1 with p300 is regulated by a phosphorylation event that changes the localization of Pdx-1. Based on these data, we conclude that hyperacetylation of histone H4 at the insulin gene promoter in response to high concentrations of glucose depends on the beta-cell specific transcription factor Pdx-1, which is required for the recruitment of the histone acetyltransferase p300 to the insulin gene promoter.
This article has been cited by other articles:
 |
|
 |
|
  H.-W. Wang, M. Muguira, W.-D. Liu, T. Zhang, C. Chen, R. Aucoin, M. B Breslin, and M. S Lan Identification of an INSM1-binding site in the insulin promoter: negative regulation of the insulin gene transcription J. Endocrinol., July 1, 2008; 198(1): 29 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Eto, V. Kaur, and M. K. Thomas Regulation of Pancreas Duodenum Homeobox-1 Expression by Early Growth Response-1 J. Biol. Chem., March 2, 2007; 282(9): 5973 - 5983. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Evans-Molina, J. C. Garmey, R. Ketchum, K. L. Brayman, S. Deng, and R. G. Mirmira Glucose Regulation of Insulin Gene Transcription and Pre-mRNA Processing in Human Islets Diabetes, March 1, 2007; 56(3): 827 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Vanderford, S. S. Andrali, and S. Ozcan Glucose Induces MafA Expression in Pancreatic Beta Cell Lines via the Hexosamine Biosynthetic Pathway J. Biol. Chem., January 19, 2007; 282(3): 1577 - 1584. [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]
|
|
|
|
 |
|
 J. Francis, D. A. Babu, T. G. Deering, S. K. Chakrabarti, J. C. Garmey, C. Evans-Molina, D. G. Taylor, and R. G. Mirmira Role of Chromatin Accessibility in the Occupancy and Transcription of the Insulin Gene by the Pancreatic and Duodenal Homeobox Factor 1 Mol. Endocrinol., December 1, 2006; 20(12): 3133 - 3145. [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. E Cerf Transcription factors regulating {beta}-cell function. Eur. J. Endocrinol., November 1, 2006; 155(5): 671 - 679. [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]
|
|
|
|
|
|
J. H Lee, J. L Volinic, C. Banz, K.-M. Yao, and M. K Thomas Interactions with p300 enhance transcriptional activation by the PDZ-domain coactivator Bridge-1 J. Endocrinol., November 1, 2005; 187(2): 283 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Iype, J. Francis, J. C. Garmey, J. C. Schisler, R. Nesher, G. C. Weir, T. C. Becker, C. B. Newgard, S. C. Griffen, and R. G. Mirmira Mechanism of insulin Gene Regulation by the Pancreatic Transcription Factor Pdx-1: APPLICATION OF PRE-mRNA ANALYSIS AND CHROMATIN IMMUNOPRECIPITATION TO ASSESS FORMATION OF FUNCTIONAL TRANSCRIPTIONAL COMPLEXES J. Biol. Chem., April 29, 2005; 280(17): 16798 - 16807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kaneto, T.-a. Matsuoka, Y. Nakatani, T. Miyatsuka, M. Matsuhisa, M. Hori, and Y. Yamasaki A Crucial Role of MafA as a Novel Therapeutic Target for Diabetes J. Biol. Chem., April 15, 2005; 280(15): 15047 - 15052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Mosley and S. Ozcan The Pancreatic Duodenal Homeobox-1 Protein (Pdx-1) Interacts with Histone Deacetylases Hdac-1 and Hdac-2 on Low Levels of Glucose J. Biol. Chem., December 24, 2004; 279(52): 54241 - 54247. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
