A beta-cell-specific protein binds to the two major regulatory sequences of the insulin gene enhancer.
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.
Ohlsson
H
H
Department of Microbiology, University of Umeå, Sweden.
Karlsson
O
O
Edlund
T
T
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005796:Genes; D005809:Genes, Regulator; D007328:Insulin / Q000235:genetics*; D007515:Islets of Langerhans / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D007328:Insulin