Imprinting and methylation

DNA methylation patterns that reflect a chromosome's parental origin are thought to regulate the establishment and maintenance of genomic imprinting. But the mechanisms controlling differential methylation and imprinting have not been elucidated. In an Advanced Online Publication in Nature Genetics Schoenherr et al. describe a role for the zinc-finger protein CTCF in maintaining methylation at the Igf2/H19 imprinted locus (Nature Genetics, 2 December 2002, DOI:10.1038/ng1057). CTCF binds to the unmethylated maternal ICR (imprinting control region) 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 re-expression 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.