DNA sequence motifs conserved in endocrine promoters are essential for Pax4 expression

The paired box transcription factor Pax4 is required for maturation of insulin-producing beta- and somatostatin secreting delta-cells in the murine pancreas. It starts to be expressed in pancreatic precursors and later is restricted to beta- and delta-cells to finally be switched off after birth. A 0.9-kb genomic DNA fragment has been shown to mediate the Pax4 expression pattern. Transcription factors Pdx1 and NeuroD bind to this fragment at A2- and E1-sequence motifs. In this study, we downscale the size of this fragment to 409 bp. Another genomic fragment of 254 bp is still able to mediate the specificity, but not the strength of Pax4 expression. Deletion of the A2 and E1 elements results in loss or weakening of reporter gene expression. Because A2 and E1 elements are conserved in numerous pancreatic promoters, they might play a general role in regulating endocrine gene expression. (C) 2003 Wiley-Liss, Inc.