EXPRESSION LEVELS OF THE INSULIN-LIKE GROWTH FACTOR-II GENE (IGF2) INTHE HUMAN LIVER - DEVELOPMENTAL RELATIONSHIPS OF THE 4 PROMOTERS

Wre have studied the insulin-like growth factor-II gene (IGF2) promote r usage in normal human liver from fetal to late adult Life by quantif ying the specific transcripts by RNase protection assays using exon-sp ecific probes. While the fetal liver uses only three promoters (P2, P3 , P4) for the transcription of IGF2, all four promoters can be used fr om the age of 2 months after birth. The levels of the individual promo ter transcripts vary substantially during development and the P3 promo ter, which is a highly active fetal promoter, was not used by all the investigated adult patients but was detected in 30% of the adult group as a whole. The P1 promoter, which has previously been considered as the only one responsible for IGF2 transcription in the postnatal/adult liver, displayed a trend of increasing relative and absolute activity throughout life, but in some adult cases it was found to be less acti ve than the P4 promoter. The P4 promoter displayed an age-related bend of decreasing activity ti-om a very high fetal level, but individual exceptions were apparent. The P2 promoter transcript, peaking at the a ge of 2 months, showed a relatively even absolute amount from 18 month s onwards. Thus, while P2 and P3 were both found to reach their highes t activity after birth, the P4 promoter displayed its highest transcri ption at the fetal stage. The total IGF2 transcription, primarily from P2, P3 and P4, was found to peak shortly after birth. After this age, the P3 promoter transcript declined most rapidly and a low or zero am ount was detected in adulthood. From the age of 18 months to old adult hood the total IGF2 mRNA, derived primarily from P1, P2 and P4, displa yed a relatively even amount (approximately one tenth) of that seen at the peak at 2 months. This data may be important in relation to trans latability of the various IGF2 transcripts.