IGF2 loss of imprinting: a potential heritable risk factor for colorectal cancer

Genomic structure of the human IGF2/H19 imprinted domain. IGF2 (9 exons; black boxes) and H19 (4 exons; stippled boxes) are reciprocally imprinted. IGF2 is expressed only from the paternal allele, whereas H19 is expressed only from the maternal allele. Regulation of IGF2 and H19 imprinting is controlled by allele-specific methylation at differentially methylated regions (DMR0) and the imprint control region (ICR). Black (methylated) and white (unmethylated) boxes above the genes indicate regions of preferential maternal (M) or paternal (P) CpG methylation. IGF2 has 4 promoters, P1–P4, that are located 5′ to exons 1, 4, 5, and 6, respectively. Enhancers (E) involved in regulating the reciprocal imprinting of IGF2 and H19 are also shown.