A direct repeat sequence at the Rasgrf1 locus and imprinted expression

Genomic imprinting is an epigenetic modification that can lead to parental- specific monoallelic expression of specific autosomal genes. While methylat ion of CpG dinucleotides is thought to be a strong candidate for this epige netic modification, little is known about the establishment or maintenance of parental origin-specific methylation patterns. We have recently identifi ed a portion of mouse chromosome 9 containing a paternally methylated regio n associated with a paternally expressed imprinted gene, Ras protein-specif ic guanine nucleotide-releasing factor 1 (Rasgrf1). This area of chromosome 9 also contains a short, direct tandem repeat in close proximity to a pate rnally methylated NotI site 30 kb upstream of Rasgrf1. Short, direct tandem repeats have been found associated with other imprinted genes and may act as important regulatory structures. Here we demonstrate that two rodent spe cies (Mus and Rattus) contain a similar direct repeat structure associated with a region of paternal-specific methylation. In both species, the Rasgrf 1 gene shows paternal-specific monoallelic expression in neonatal brain. A more divergent rodent species (Peromyscus) appears to lack a similar repeat structure based on Southern Blot analysis. Peromyscus animals show biallel ic expression of Rasgrf1 in neonatal brain. These results suggest that dire ct repeat elements may play an important role in the imprinting process. (C ) 1999 Academic Press.