Abstract
The pancreas-specific transcription factor Pdx-1 is important for pancreas development and β-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.
| Original language | English |
|---|---|
| Pages (from-to) | 724-729 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 295 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2002 |
Bibliographical note
Funding Information:This work was supported by a Juvenile Diabetes Foundation Career Development Award (to S.O.) We thank Alan Permutt (Washington University, St. Louis) for providing the cDNA for the mouse PDX-1 gene, Michael German (UCSD) for the plasmid containing the A3 region, and Fang Fang for excellent technical assistance.
Keywords
- Activator
- Gene expression
- Pancreas
- Pdx-1
- Transcription factor
- Yeast
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
