A beta-cell-specific protein binds to the two major regulatory sequences of the insulin gene enhancer.
AUTOR(ES)
Ohlsson, H
RESUMO
The selective transcription of the Rat insulin 1 gene is mainly dependent on a beta-cell-specific enhancer element located in the 5' flanking DNA. In analogy to many other viral and cellular enhancers, the insulin enhancer has been shown to be of a mosaic structure and the cis-acting elements of importance for the enhancer activity have been defined. Two short sequences are of crucial importance for the enhancer activity since mutation of either sequence leads to a decrease in activity (by a factor of approximately 10), and the double mutant eliminates all enhancer activity. This study shows that these two major cis-acting elements interact with beta-cell-specific proteins. These two enhancer modules carry an 8-base-pair homology and compete with each other for protein binding, suggesting that they interact with the same protein, designated insulin enhancer binding factor 1 (IEF 1). Since mutation of these sequences eliminates the enhancer activity and protein binding, we propose that IEF 1 is the key regulator controlling the selective activity of the insulin gene enhancer.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=280400Documentos Relacionados
- Individual protein-binding domains of the insulin gene enhancer positively activate beta-cell-specific transcription.
- Hepatocyte nuclear factor 3beta is involved in pancreatic beta-cell-specific transcription of the pdx-1 gene.
- A novel POU domain protein which binds to the T-cell receptor beta enhancer.
- Extinction of insulin gene expression in hybrids between beta cells and fibroblasts is accompanied by loss of the putative beta-cell-specific transcription factor IEF1.
- A mutational analysis of the insulin gene transcription control region: expression in beta cells is dependent on two related sequences within the enhancer.
