This Article Full Text Full Text (PDF) All Versions of this Article: 18/3/533    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gerrish, K. Articles by Stein, R. Search for Related Content PubMed PubMed Citation Articles by Gerrish, K. Articles by Stein, R.

Conserved Transcriptional Regulatory Domains of the pdx-1 Gene

Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37215

Address all correspondence and requests for reprints to: Roland Stein, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 723 Light Hall, Nashville, Tennessee 37215. E-mail: roland.stein{at}vanderbilt.edu.

The pancreas and duodenum homeobox protein 1 (PDX-1) homeodomain-containing transcription factor affects both pancreatic endocrine cell development and adult islet ß-cell function. Cell-type-specific expression is controlled by sequences 5' flanking the pdx-1 gene transcription start site. One principal control region is located roughly between -2800 and -1600 bp and spans three conserved, distinct, and functionally important subdomains, termed areas I, II, and III. In this study, we found that an upstream control region in the rat pdx-1 gene located between -6200 and -5670 bp is also present in the mouse, chicken, and human genes. This region is capable of independently directing pancreatic ß-cell-selective reporter gene expression and potentiating area I/II-driven activity. This newly recognized conserved subdomain has been termed area IV. The islet-enriched forkhead box A2 (FoxA2), NK2 homeobox 2.2 (Nkx2.2), and pancreas and duodenum homeobox protein 1 (PDX-1) transcription factors have been shown to activate area IV-driven reporter gene expression as well as bind to this region of the endogenous gene in ß-cells. Analysis of the histone H3 and H4 acetylation level also indicated that areas I–IV are within transcriptionally active chromatin in ß-cells. Our data suggests that pdx-1 transcription is also regulated by factors acting upon conserved area IV sequences.

This article has been cited by other articles:

				P. O. Wiebe, J. D. Kormish, V. T. Roper, Y. Fujitani, N. I. Alston, K. S. Zaret, C. V. E. Wright, R. W. Stein, and M. Gannon Ptf1a Binds to and Activates Area III, a Highly Conserved Region of the Pdx1 Promoter That Mediates Early Pancreas-Wide Pdx1 Expression Mol. Cell. Biol., June 1, 2007; 27(11): 4093 - 4104. [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]

				J. C. Raum, K. Gerrish, I. Artner, E. Henderson, M. Guo, L. Sussel, J. C. Schisler, C. B. Newgard, and R. Stein FoxA2, Nkx2.2, and PDX-1 Regulate Islet {beta}-Cell-Specific mafA Expression through Conserved Sequences Located between Base Pairs -8118 and -7750 Upstream from the Transcription Start Site Mol. Cell. Biol., August 1, 2006; 26(15): 5735 - 5743. [Abstract] [Full Text] [PDF]

				B. Desvergne, L. Michalik, and W. Wahli Transcriptional Regulation of Metabolism Physiol Rev, April 1, 2006; 86(2): 465 - 514. [Abstract] [Full Text] [PDF]

				Y. Fujitani, S. Fujitani, D. F. Boyer, M. Gannon, Y. Kawaguchi, M. Ray, M. Shiota, R. W. Stein, M. A. Magnuson, and C. V.E. Wright Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation Genes & Dev., January 15, 2006; 20(2): 253 - 266. [Abstract] [Full Text] [PDF]

				J. C. Van Velkinburgh, S. E. Samaras, K. Gerrish, I. Artner, and R. Stein Interactions between Areas I and II Direct pdx-1 Expression Specifically to Islet Cell Types of the Mature and Developing Pancreas J. Biol. Chem., November 18, 2005; 280(46): 38438 - 38444. [Abstract] [Full Text] [PDF]

				D. K. Hagman, L. B. Hays, S. D. Parazzoli, and V. Poitout{paragraph} Palmitate Inhibits Insulin Gene Expression by Altering PDX-1 Nuclear Localization and Reducing MafA Expression in Isolated Rat Islets of Langerhans J. Biol. Chem., September 16, 2005; 280(37): 32413 - 32418. [Abstract] [Full Text] [PDF]