DEVELOPMENTAL-DEPENDENT DNA METHYLATION OF THE IGF2 AND H19 PROMOTERSIS CORRELATED TO THE PROMOTER ACTIVITIES IN HUMAN LIVER DEVELOPMENT

We have previously shown that the four promoters of the IGF2 gene are under a tight but dynamic control during human liver development, wher eby P3 and P1 are reciprocally active before and after birth respectiv ely while the P2 and P4 promoters are constitutively active at a relat ively lower level. In this study, we investigated the methylation stat us of the promoters P1 and P3 of IGF2 and the promoter region of the H 19 gene in developing human livers ranging from fetal to late adult. A region of about 300bp immediately upstream of the IGF2 exon 5 was fou nd to be subjected to a developmental-specific methylation and this ma y correlate to the P3 promoter activity. The P1 domain of IGF2 was als o found to be methylated in a developmentally-specific pattern. The pr omoter region of the H19 gene displayed different methylation patterns in different development stages showing decreased general methylation with increase of age. Therefore, regional- and developmental-specific DMA methylation is displayed in the promoter regions of the IGF2 and H19 genes. This may be an important factor involved in gene regulation in the developing human liver.