The human insulin-like growth factor-II promoter P1 is not restricted to liver: evidence for expression of P1 in other tissues and for a homologous promoter in baboon liver.

Abstract

The human insulin-like growth factor (IGF)-II gene (IGF2) contains 4 different promoters (P1-P4), three of which (P2-P4) are homologous to the 3 promoters found in murine IGF-II genes. IGF-II is abundantly expressed in adult humans and primates, but IGF2 is only expressed in brain in adult rat and mouse. Previously, promoter P1 had been found exclusively in human adult liver but not in other human tissues or in rat or mouse liver. Although mouse liver does not express a homologue of human P1 mRNA, 5' "pseudo-exons" which are homologues of human exons 2 and 3 have been identified in murine IGF2. Based on the published DNA sequences of human exon 2 and the homologous murine pseudo-exon psi 1, we designed a 5'-oligonucleotide common to both human and murine IGF2 and a 3'-oligonucleotide primer from coding exon 7. We amplified specific cDNA from human and baboon livers, but no specific band was seen in rat or mouse liver. Chain-termination DNA sequencing confirmed that the P1 mRNA sequence from baboon liver shares 90% homology with human P1 mRNA in the 5' noncoding region (exons 2 and 3). Mature baboon IGF-II peptide is identical to human IGF-II, but there are 7 amino acid differences in the E region of the IGF-II prohormone. In humans, IGF-II mRNA transcripts containing P1 were also found in human myometrium and myomas. Our results demonstrate that the P1 promoter of the IGF-II gene is present in human and baboon adult liver, although it is absent from murine liver. In humans, promoter P1 is also utilized in tissues other than adult liver. We speculate that promoter P1 may be an important factor in persistent IGF-II synthesis.