Maternal-Specific Methylation of the HumanIGF2RGene Is Not Accompanied by Allele-Specific Transcription

The human insulin-like growth factor type 2 receptor gene (IGF2R) is biallelically expressed in a variety of fetal and adult tissues. In contrast, the imprinted mouseIgf2rgene is expressed exclusively from the maternally inherited chromosome. The mouse gene contains two CpG islands that are methylated in a parent-specific manner. Methylation of the CpG island in the promoter region occurs on the repressed paternal gene copy. Methylation of the CpG island in intron 2 is specific for the active maternal allele and may represent the primary imprint. Here, we have analyzed the humanIGF2Rgene to investigate whether these motifs and their parent-of-origin-specific epigenetic modification have been conserved. As in the mouse, the humanIGF2Rgene was found to contain two CpG islands, one encompassing the transcription start site (CpG 1) and the other in the second intron (CpG 2). CpG 2 is hypermethylated on the maternalIGF2Rallele. In contrast to the situation in the mouse, however, the human CpG 1 is completely unmethylated on both parental chromosomes. The human and mouse intronic CpG islands lack significant sequence homology, which suggests that DNA conformation plays a role in allele-specific methylation.