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Submitted on September 23, 2003
Accepted on December 17, 2003
1 Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 723 Light Hall, Nashville, TN 37215
* To whom correspondence should be addressed. E-mail: roland.stein{at}vanderbilt.edu.
The PDX-1 homeodomain-containing transcription factor affects both pancreatic endocrine cell development and adult islet
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 to -1600 base pairs (bp) and spans three conserved, distinct, and functionally important sub-domains, 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 to -5670 bp is also present in the mouse, chicken, and human genes. This region is capable of independently directing pancreatic
cell-selective reporter gene expression, and potentiating Area I/II-driven activity. This newly recognized conserved sub-domain has been termed Area IV. The islet-enriched FoxA2, Nkx2.2, and 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
cells. Analysis of the histone H3 and H4 acetylation level also indicated that Areas I-IV are within transcriptional active chromatin in
cells. Our data suggests that pdx-1 transcription is also regulated by factors acting upon conserved Area IV sequences.
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