Characterization of the differentially methylated region of the Impact gene that exhibits Glires-specific imprinting
1 The Centre for Applied Genomics, Program in Genetics and Genome Biology, The Hospital for Sick Children, MaRS Centre TMDT, 101 College Street, Toronto, Ontario M5G 1L7, Canada
2 Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada
3 Current address: Human Genome Centre, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato Ward, Tokyo 108-8639, Japan
Genome Biology 2008, 9:R160 doi:10.1186/gb-2008-9-11-r160Published: 13 November 2008
Imprinted genes are exclusively expressed from one of the two parental alleles in a parent-of-origin-specific manner. In mammals, nearly 100 genes are documented to be imprinted. To understand the mechanism behind this gene regulation and to identify novel imprinted genes, common features of DNA sequences have been analyzed; however, the general features required for genomic imprinting have not yet been identified, possibly due to variability in underlying molecular mechanisms from locus to locus.
We performed a thorough comparative genomic analysis of a single locus, Impact, which is imprinted only in Glires (rodents and lagomorphs). The fact that Glires and primates diverged from each other as recent as 70 million years ago makes comparisons between imprinted and non-imprinted orthologues relatively reliable. In species from the Glires clade, Impact bears a differentially methylated region, whereby the maternal allele is hypermethylated. Analysis of this region demonstrated that imprinting was not associated with the presence of direct tandem repeats nor with CpG dinucleotide density. In contrast, a CpG periodicity of 8 bp was observed in this region in species of the Glires clade compared to those of carnivores, artiodactyls, and primates.
We show that tandem repeats are dispensable, establishment of the differentially methylated region does not rely on G+C content and CpG density, and the CpG periodicity of 8 bp is meaningful to the imprinting. This interval has recently been reported to be optimal for de novo methylation by the Dnmt3a-Dnmt3L complex, suggesting its importance in the establishment of imprinting in Impact and other genes.