CTCF is a zinc finger DNA-binding protein that regulates the epigenetic states 
of numerous target genes. Using allelic regulation of mouse insulin-like growth 
factor II (Igf2) as a model, we demonstrate that CTCF binds to the unmethylated 
maternal allele of the imprinting control region (ICR) in the Igf2/H19 
imprinting domain and forms a long-range intrachromosomal loop to interact with 
the three clustered Igf2 promoters. Polycomb repressive complex 2 is recruited 
through the interaction of CTCF with Suz12, leading to allele-specific 
methylation at lysine 27 of histone H3 (H3-K27) and to suppression of the 
maternal Igf2 promoters. Targeted mutation or deletion of the maternal ICR 
abolishes this chromatin loop, decreases allelic H3-K27 methylation, and causes 
loss of Igf2 imprinting. RNA interference knockdown of Suz12 also leads to 
reactivation of the maternal Igf2 allele and biallelic Igf2 expression. CTCF and 
Suz12 are coprecipitated from nuclear extracts with antibodies specific for 
either protein, and they interact with each other in a two-hybrid system. These 
findings offer insight into general epigenetic mechanisms by which CTCF governs 
gene expression by orchestrating chromatin loop structures and by serving as a 
DNA-binding protein scaffold to recruit and bind polycomb repressive complexes.