A direct repeat sequence at the Rasgrf1 locus and imprinted expression

• Published in: Genomics (San Diego, Calif.) Vol. 55; no. 2; pp. 194 - 201
• Main Authors: PEARSALL, R. S, PLASS, C, ROMANO, M. A, GARRICK, M. D, SHIBATA, H, HAYASHIZAKI, Y, HELD, W. A
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier 15.01.1999
• Subjects: Animals; Base Sequence; Biological and medical sciences; Blotting, Southern; Brain - embryology; Brain - metabolism; Chromosome Mapping; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Genomic Imprinting; Guanine Nucleotide Exchange Factors; Lung - embryology; Lung - metabolism; Mice; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Muridae; Peromyscus; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Proteins - genetics; ras Guanine Nucleotide Exchange Factors; ras Proteins; Rats; Repetitive Sequences, Nucleic Acid - genetics; Reverse Transcriptase Polymerase Chain Reaction; Species Specificity; Transcription. Transcription factor. Splicing. Rna processing; Neonatal; Rat; Nucleotide sequence; Rodentia; Tissue specificity; Gene expression; Tandemly repeated sequence; Genomic imprinting; Paternal origin; Vertebrata; Mammalia; Mouse; Brain (invertebrata); Epigenetics; Methylation
• DOI: 10.1006/geno.1998.5660
• ISSN: 0888-7543

Genomic imprinting is an epigenetic modification that can lead to parental-specific monoallelic expression of specific autosomal genes. While methylation of CpG dinucleotides is thought to be a strong candidate for this epigenetic modification, little is known about the establishment or maintenance of parental origin-specific methylation patterns. We have recently identified a portion of mouse chromosome 9 containing a paternally methylated region associated with a paternally expressed imprinted gene, Ras protein-specific guanine nucleotide-releasing factor 1 (Rasgrf1). This area of chromosome 9 also contains a short, direct tandem repeat in close proximity to a paternally 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 species (Mus and Rattus) contain a similar direct repeat structure associated with a region of paternal-specific methylation. In both species, the Rasgrf1 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 biallelic expression of Rasgrf1 in neonatal brain. These results suggest that direct repeat elements may play an important role in the imprinting process.