The elastase I (EI) gene is a representative member of the serine protease gene family selectively expressed in the acinar cells of the exocrine pancreas. The rigorous cell-specific transcription of the EI gene provides a simple paridigm of transcriptional regulation. Transcription of the EI gene is controlled by a short (134 bp) enhancer which can direct the expression of foreign genes selectively to the pancreas of transgenic mice or in a pancreatic cultured cell line. Toward our long-term goal of understanding the mechanism of cell-specific control of transcription in animals, we will identify the functional elements within the EI enhancer and the trans-acting factors necessary for enhancer function.
The specific aims of this proposal are: (1) To define precisely the functional DNA sequence motifs within the EI enhancer and their role in cell-specific enhancer action. Individual motifs will be tested for their ability to act as cell-specific enhancers in both cultured cells and transgenic animals. (2) To identify, purify, and characterize the transcription factors which act upon the EI enhancer. (3) To clone the mRNAs for the DNA-binding transcription factors that determine the cell-specific action of the EI enhancer. (4) To determine which of the factors (or combination of factors) is necessary for EI gene expression by introducing the cloned transcription factor genes into nonpancreatic cells in culture or into transgenic animals. (5) To determine the biochemical role of individual factors in cell- specific or general transcription by devising a cell-free transcription system that requires pancreatic nuclear factors to transcribe the EI gene.
| Viswanath, R L; Rose, S D; Swift, G H et al. (2000) A binary mechanism for the selective action of a pancreatic beta -cell transcriptional silencer. J Biol Chem 275:40273-81 |
| Swift, G H; Liu, Y; Rose, S D et al. (1998) An endocrine-exocrine switch in the activity of the pancreatic homeodomain protein PDX1 through formation of a trimeric complex with PBX1b and MRG1 (MEIS2). Mol Cell Biol 18:5109-20 |
| MacDonald, R J; Swift, G H (1998) Analysis of transcriptional regulatory regions in vivo. Int J Dev Biol 42:983-94 |
| Kruse, F; Komro, C T; Michnoff, C H et al. (1988) The cell-specific elastase I enhancer comprises two domains. Mol Cell Biol 8:893-902 |
| Davis, B P; MacDonald, R J (1988) Limited transcription of rat elastase I transgene repeats in transgenic mice. Genes Dev 2:13-22 |
