Cell-specific expression of the rat insulin gene: evidence for role of two distinct 5' flanking elements

The 5' flanking DNA of the rat insulin I gene contains sequences controlling cell-specific expression. Analysis of this region by replacement of specific portions with nondiscriminatory control elements from viral systems shows that a transcriptional enhancer is located in the distal portion of the 5' flanking DNA; its position has been mapped by deletion analysis. Additional experiments suggest that another distinct regulatory element is located more proximal to the transcription start site. The activity of both elements is restricted to pancreatic B cells. The combinatorial effect of multiple control elements could explain the cell-specific expression of insulin genes.