TRANSCRIPTIONAL REGULATION AND PARENTAL IMPRINTING OF IGF2 DURING HUMAN EMBRYONIC-DEVELOPMENT

We provide here an overview of the transcriptional regulation of human IGF2 in the developing embryo. IGF2 expression is governed by at least four promoters designated P1-P4. During embryonic/fetal development, exclusively the promoters P2-P4 are used, albeit to varying degree, in all tissues expressing the gene. Some time after birth, there is a switch in promoter usage in the liver, so that Pl is activated. In addition, the P2-P4 promoters are active in other postnatal tissues, such as pregnant and nonpregnant decidua. We have shown that only the paternally-inherited/GF2 allele is transcriptionally active, e.g. parentally imprinted, during human embryogenesis. In situ hybridization analyses of both IGF-II and IGF type 1 receptor expression patterns visualize potential local functions of IGF-II. We discuss these data in relation to human disease syndromes, such as the Beckwith-Wiedemann syndrome.