Ekaterina Vlasova

Mentor: Tamara Davis

CpG Dyad Methylation Patterns at DMR of Gene Gtl2

A small fraction of mammalian genes are regulated by genomic imprinting. Genomic imprinting is a type of epigenetic regulatory mechanism. Unlike sequence-based gene regulation, genomic imprinting influences gene expression via heritable modifications to DNA. These include DNA methylation and histone modification. For approximately 150 genes, genomic imprinting results in monoallelic gene expression.

Understanding the mechanisms of imprinting has broad implications for human health. Proper regulation of imprinted genes is essential for normal patterns of growth and development. Many of the diseases associated with imprinted genes involve variations of growth or feeding disorders. Therefore, developing a more comprehensive understanding of the mechanisms associated with genomic imprinting is essential for the detection and treatment of developmental disorders and disease.

Previous analysis of the differentially methylated region (DMR) of imprinted gene Dlk1 revealed an unusual methylation pattern. Methylation, the addition of a methyl group to cytosine, occurs at CpG dinucleotides. The Dlk1 study revealed an unexpected asymmetry of methylation in a large fraction of the complementary CpG dinucleotides. Approximately 35% of CpG dyads were hemi-methylated, meaning that only one CpG dinucleotide of the complementary pair was methylated. A possible explanation for this may be that the maintenance of DNA methylation might be less efficient at secondary DMR sites than at primary imprinting control regions.

In order to test whether this pattern of methylation is unique to Dlk1 or if it is a hallmark of other imprinted genes, a similar analysis will be undertaken for the DMR associated with imprinted gene Gtl2. This analysis will look at several stages of development across several tissues from Mus musculus, in order to elucidate the temporal and tissue-specific methylation pattern acquisition. Further analysis of the CpG dyad methylation patterns may provide insight into the mechanisms of methylation acquisition and maintenance at the Gtl2 DMR.