Model of the IGF2/H19 imprinting region. Aberrant IGF2 imprinting induced by the decoy CTCF. In cells that maintain normal IGF2 imprinting, CTCF orchestrates an intrachromosomal loop by binding to both the unmethylated ICR and to the IGF2 promoters on the maternal allele. CTCF then dimerizes, tethering the loop together. CTCF interacts with SUZ12 in PRC2, thereby guiding the K27 methylase EZH2 to the IGF2 promoters, where it methylates histone H3 and causes the allele-specific suppression of the maternal promoters. When the decoy CTCF binds to the ICR, it fails to recruit SUZ12, thus abrogating the IGF2 promoters/ICR intrachromosomal loop. Without the CTCF–PRC2 interaction, EZH2 cannot methylate H3-K27 in the IGF2 promoters, resulting in the reactivation of the normally suppressed maternal allele.