Nicole Hamagami

Mentor: Dr. Tamara L. Davis

Department: Biology

Analysis of DNA Methylation on the Complementary Strands of the Imprinted p57 Gene

Genomic imprinting is a mammalian specific epigenetic mechanism that facilitates the expression of one parental allele over the other. Epigenetic factors function to regulate the expression state by attracting or repelling various elements required for DNA transcription. Differential distribution of such epigenetic modifications on the parental alleles therefore results in their differential expression. One such modification is DNA methylation, which regulates gene expression by promoting the methylation of cytosine bases in DNA on one parental allele, thereby transcriptionally silencing that allele compared to the other.

The proper regulation of imprinted genes is important for normal development and failure to achieve genomic imprinting can lead to various genetic disorders. The study of imprinted genes is therefore crucial in better understanding the mechanisms behind normal embryonic development, as well as specific genetic disorders such as Angelman syndrome and Prader-Willi syndrome. Research has led to the identification of approximately 120 genes that undergo genomic imprinting. All of these genes are associated with DNA methylation, illustrating the importance of this epigenetic modification to the regulation of these genes.

However, the magnitude and consistency of DNA methylation varies at different imprinted genes. We are currently examining differentially methylated regions (DMRs) across a group of imprinted genes with varied patterns of methylation to understand the importance of the stability and consistency of this modification for proper regulation of imprinted expression. Previous analysis at the DMR of the imprinted gene Dlk1 revealed a possible correlation between its unusually variable methylation pattern and its high incidence of hemimethylation, or methylation on only one of the two complementary strands, which may be indicative of a loss of methylation over time. In order to determine whether this correlation is unique to Dlk1 or is a universal feature at other imprinted genes, we will perform a similar analysis at p57 DMR, another imprinted gene with a highly variable methylated region, across several stages of development. Analysis of p57 will provide further insight into the mechanism of DNA methylation pattern maintenance and serve as a point for comparison against other DMRs that show more versus less consistent methylation patterns.