Imprinting and methylation

Parental-specific DNA methylation patterns are thought to regulate the establishment and maintenance of genomic imprinting. But the mechanisms controlling differential methylation and imprinting have been unclear. In an Advanced Online Publication in Nature Genetics, Christopher Schoenherr and colleagues describe a role for the zinc-finger protein CTCF in maintaining methylation at the Igf2/H19 imprinted locus (Nature Genetics, DOI:10.1038/ng1057, December 2, 2002).

CTCF binds to the unmethylated maternal imprinting control region (ICR) to create a chromatin boundary between the Igf2 and H19 genes. Schoenherr et al. generated mice with a mutated ICR that bound CTCF very poorly. The mutation resulted in methylation of the maternal ICR allele and reexpression of the maternal Igf2 gene and reduced H19 expression levels. Thus, CTCF binding appears to protect from methylation and is essential for the maintenance of differential methylation and imprinting patterns. CTCF is important for establishing the chromatin boundaries that regulate transcriptional territories.