Functional expression and analysis of the pancreatic transcription factor PDX-1 in yeast

The pancreas-specific transcription factor Pdx-1 is important for pancreas development and beta-cell specific gene expression in insulin-producing cells. We have expressed the mouse PDX-1 gene in the yeast Saccharomyces cerevisiae and characterized its functional domains. Pdx-1 functions as a strong activator in yeast and stimulates gene expression by more than 80-fold. The transcriptional activation domain of Pdx-1 is located within the first 144 amino-terminal amino acids. Pdx-1 is also able to bind and activate transcription from the A3 element of the human insulin gene promoter in yeast. Analysis of the effects of two-point mutations (Q59L and R197H) in the PDX-1 gene found in type II diabetes patients showed that both point mutations interfere with the ability of Pdx-1 to bind to DNA and to activate transcription in yeast.