To continue the characterization of pancreatic gene expression, the applicant proposes a analysis of the transcriptional control of pancreatic development: The investigator will test the role of the key pancreatic acinar transcription factor PTF1 in pancreogenesis. The acinar cell-specific transcription of the pancreatic elastase I (EI) gene provides a simple paradigm of transcriptional regulation during organogenesis. Transcription is controlled by three elements (A, B and C) within a tissue- specific enhancer that specifies the level and pancreas-specificity of transcription. A repressor region immediately upstream of the enhancer restricts expression to the acinar cells. The A element binds an acinar cell- specific transcription factor (PTF1) and is the sole positively acting element that directs acinar cell-specific transcription of the other acinar cell- specific genes as well. The investigator proposes that PTF1 plays a pleiotropic role in the embryonic development of the exocrine pancreas. Cloning the genes for one or more PTF1 subunits, followed by creation and analysis of PTF1-deficient homozygous mice will test the role of PTF1 in exocrine gene transcription and in pancreatic organ formation.
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