Expression of the trans-active factors that stimulate insulin control element-mediated activity appear to precede insulin gene transcription

Abstract

Cell type-specific expression of the major differentiated products of alpha (glucagon) and beta (insulin) cells are regulated by sequences found within their 5'-flanking region. Specific transcription of the insulin gene appears to be principally controlled by a single cis-acting DNA element, termed the insulin control element (ICE). The ICE activator acts in combination with other positive regulatory factors that interact within this region to generate the correct, cell type-specific expression. In the present study, we show that the ICE activator is not only present but is functionally active in the islet glucagon-producing alpha cell line, alpha TC6. Analysis of the expression of various transfected insulin enhancer expression plasmids demonstrated that the insulin enhancer is active in alpha TC6 cells, although at a lower level than in beta cells. The reduced transcription from these constructs appears to be a consequence of the lack of other essential positive regulator(s). The alpha TC6 cells were also shown to display neuronal-like properties. Since islet cells appear to evolve from an alpha-like precursor cell that transiently expresses neuronal cell markers, these results would indicate that the ICE activator factor is induced before transcription of the insulin gene in the developing islet.