Transcriptional and post-transcriptional regulation of the human IGF-II gene expression

The human insulin-like growth factor II (IGF-II) gene consists of nine exons and has four promoters (P1-4). The promoters exhibit a tissue-specific and developmental stage-dependent expression pattern. In fetal liver promoters P2-4 are expressed, but after birth these promoters are shut off and another promoter, P1, is activated. We have investigated some properties of the human promoters P1 and P3 and identified a number of sequence elements, that are recognized by transcription factors. Promoter P1 is stimulated by the liver-enriched transcription factors C/EBP and LAP, whereas in the proximal region of P3 we have identified several elements that are recognized by transcription factors, including krox20/egr2 and krox24/erg1. Besides transcriptional regulation of expression also regulation at the post-transcriptional level occurs. We have found that the IGF-II mRNAs are subjected to site-specific endonucleolytic cleavage yielding a labile 5' specific fragment and a stable polyadenylated 3' specific cleavage product of 1.8 kb. Two widely separated sequence elements within the last exon were identified that are able to interact and yield a double-stranded stem structure. It is likely that this structure is essential for post-transcriptional cleavage of IGF-II mRNAs.