MATERNAL-SPECIFIC METHYLATION OF THE HUMAN IGF2R GENE IS NOT ACCOMPANIED BY ALLELE-SPECIFIC TRANSCRIPTION

The human insulin-like growth factor type 2 receptor gene (ICF2R) is b iallelically expressed in a variety of fetal and adult tissues. In con trast, the imprinted mouse Igf2r gene is expressed exclusively from th e maternally inherited chromosome. The mouse gene contains two CpG isl ands that are methylated in a parent-specific manner. Methylation of t he CpG island in the promoter region occurs on the repressed paternal gene copy. Methylation of the CpG island in intron 2 is specific for t he active maternal allele and may represent the primary imprint. Here, we have analyzed the human IGF2R gene to investigate whether these mo tifs and their parent-of-origin-specific epigenetic modification have been conserved. As in the mouse, the human IGF2R gene was found to con tain two CpG islands, one encompassing the transcription start site (C pG 1) and the other in the second intron (CpG 2). CpG 2 is hypermethyl ated on the maternal IGF2R allele. In contrast to the situation in the mouse, however, the human CpG 1 is completely unmethylated on both pa rental chromosomes. The human and mouse intronic CpG islands lack sign ificant sequence homology, which suggests that DNA conformation plays a role in allele-specific methylation. (C) 1996 Academic Press, Inc.