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 PI 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/egrl.
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.
KeywordsElectrophoretic Mobility Shift Assay Hep3B Cell Endonucleolytic Cleavage Electrophoretic Mobility Shift Analysis Cleavage Unit
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