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.
Sussenbach
J S
JS
Laboratory for Physiological Chemistry, Utrecht University, The Netherlands.
Rodenburg
R J
RJ
Scheper
W
W
Holthuizen
P
P
D000818:Animals; D001483:Base Sequence; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II