DISSOCIATION OF IGF2 AND H19 IMPRINTING IN HUMAN BRAIN

The human IGF2 and H19 genes are imprinted in most normal tissues. Alt erations of genomic imprinting or loss of imprinting (LOI) have been o bserved in a number of malignant tumors. Although LOI has been linked to tumorigenesis, loss of IGF2 imprinting has also been observed in ch oroid plexus and leptomeninges in normal mouse brain. We have therefor e analyzed the allelic expression of both IGF2 and H19 in human fetal brain and in different regions of human adult brain. In the brains of fetuses of 6-12 weeks gestation, both IGF2 and H19 were transcribed fr om both parental alleles. In contrast, strictly monoallelic expression of both IGF2 and H19 was observed in all other fetal tissues, suggest ing a tissue-specific LOI in the central nervous system. In adult brai n, LOI of IGF2 was region-specific. IGF2 was expressed from both paren tal alleles in the pens, but not in globus palludus, Raphe nucleus and hypothalamus. H19 expression was drastically reduced in adult brain c ompared to fetal brain, and was detectable only in the pens and globus palludus. In contrast to IGF2, the expression of H19 in adult pens wa s monoallelic. Examination of IGF2 promoter usage indicated predominan t utilization of promoter P3 in all fetal and adult brain tissues. The LOI of IGF2 therefore reflects biallelic expression from the predomin ant promoter. IGF2 transcripts derived from the less abundant promoter P1, however, showed monoallelic expression in the adult pens. Our res ults suggest that IGF2 and H19 undergo ontogenetic changes in allelic expression and that there is dissociation of IGF2 and H19 imprinting i n both fetal and adult human brain. (C) 1998 Elsevier Science B.V. All rights reserved.