Figure 3.

CTCF is the major epigenetic organizer of the maternal allele in the soma. (A) Domain-wide allele-specific epigenetic features of the H19/Igf2 imprinted domain. DNA methylation is paternal allele-specific in the ICR and at the H19 promoter. Methylation is also paternally biased at the Igf2 promoter and DMR2 (lollipops with shades of gray). Histone covalent modificatons are polarized along the domain. Active chromatin marks (green hexagon) exist at the active gene copies and in the maternal ICR but repressive marks (red hexagon) exist in the silent gene copies and the paternal ICR. (B) CTCF binding in the ICR is required for domain-wide epigenetic features. The maternal chromosome that carries CTCF binding site mutations (M_CTCFm) becomes very similar to the normal paternal chromosome in each epigenetic feature, DNA methylation and chromatin composition. Vertical arrows in (A) depict the changes in enrichment of active (green) and repressive (red) chromatin marks at the Igf2 or H19 regions that occur in response to CTCF site mutations.