Initial characterization of the four promoters of the human insulin-like growth factor II gene.

The human insulin-like growth factor II (IGF-II) gene contains four promoters (P1-P4), which are expressed in a tissue-specific and development-dependent way. Analysis of IGF-II mRNAs in different tissues has revealed that promoters P3 and P4 are expressed in all fetal and in nonhepatic adult tissues. In adult liver, however, the promoters P2, P3 and P4 are completely shut off and another promoter, P1, is activated. To obtain more insight in the mechanisms involved in the regulation of IGF-II gene expression we have performed an initial characterization of the IGF-II promoters employing transient expression of IGF-II promoter constructs in Hep3B and HeLa cells. These studies have revealed that promoters P1, P3 and P4 are active in both cell lines tested, while no activity of promoter P2 could be detected. Employing gel retardation and DNaseI footprint analysis we have identified in the three IGF-II promoters a number of elements which are bound by nuclear proteins.