CONSERVATION OF A MATERNAL-SPECIFIC METHYLATION SIGNAL AT THE HUMAN IGF2R LOCUS

The human IGF2R gene has been reported to be either biallelically or v ery rarely monoallelically expressed, in contrast to the maternally ex pressed mouse counterpart. We describe here an analysis of the 5' port ion of the human IGF2R gene and show that it contains a maternally met hylated CpG island in the second intron, A similar maternally methylat ed intronic element has been proposed to be the imprinting box for the mouse gene and although the relevance of this element has yet to be d irectly demonstrated, methylation has been reported to be essential to maintain allele-specific expression of imprinted genes, Allelic expre ssion analysis of human IGF2R in 70 lymphoblastoid cell lines identifi ed only one line showing monoallelic expression, Thus, in this tissue monoparental methylation of the IGF2R gene does not correlate with all ele-specific expression, We also confirm here that the human IGF2R gen e is located in an asynchronously replicating chromosomal region, as a re all other imprinted genes so far analyzed. The mouse and human IGF2 R intronic CpG islands both contain numerous large direct repeats that are methylated following maternal, but not paternal, transmittance. T hus features that attract maternal-specific methylation are conserved between the mouse and human genes. Since these intronic CPG islands sh are organizational rather than sequence homology, this suggests that s econdary DNA structure may play a role in attracting a maternal methyl ation imprint.