FIG. 6.

Simplified model of regulation of Igf2 imprinting by the CTCF-mediated PRC2-Igf2 promoter suppressive complex. CTCF binds to the unmethylated ICR and the Igf2 promoters on the maternal allele and forms a long-distance intrachromosomal loop through CTCF dimerization. CTCF recruits PRC2 via Suz12, resulting in methylated H3-K27 and inactive chromatin around the Igf2 promoters. On the paternal allele, the methylated ICR does not bind CTCF and the CTCF-PRC2 suppression complex cannot be formed, resulting in unmethylated H3-K27 in the active Igf2 promoters. Similarly, CTCF-mediated ICR-promoter looping is abolished when the CTCF binding site in the ICR is deleted or mutated. Loss of H3-K9 methylation at the maternal promoters leads to loss of Igf2 imprinting.