EXTINCTION OF THE HUMAN INSULIN GENE-EXPRESSION IN INSULINOMA X FIBROBLAST SOMATIC-CELL HYBRIDS INVOLVES CIS-ACTING DNA ELEMENTS

Insulin gene expression in rat insulinoma (RIN) cells is extinct in RIN x fibroblast hybrids and can reappear upon loss of DNA contributed by the fibroblast parent. (Besnard et al., Exp. Cell Res. 185:101-108, 1989). In the present study, we looked for the role of 5'-flanking sequences of the human insulin gene in the negative control observed in the hybrids. RIN cells were transformed with composite genes which consisted of the coding sequence of the gpt gene placed under the control of 5'-flanking regions of the human insulin gene (Ins. gpt gene). Upon hybridization of these cells with mouse fibroblasts, the expression of both Ins.gpt and endogenous rat insulin genes were suppressed together. The results obtained indicate that cis-acting DNA elements are involved in the negative control of the gene. These elements are located in a fragment spread from - 258 to + 241 of the transcription origin of the human insulin gene.