Mentor: Dr. Tamara Davis
While most genes are biallelically expressed, a small number of mammalian genes exhibit differential expression whereby one parent’s allele is expressed and the other is silenced. This process is known as genomic imprinting. Parental alleles must be marked to allow cellular machinery to distinguish between them and regulate their expression appropriately. Mechanisms hypothesized to be involved in this distinction include methylation of CpG dinucleotides, replication timing, chromatin structure, and repetitive sequences (Brannan et al. 1999). My research focuses on the significance of differential methylation at the p57 gene in mice.
The p57 gene is maternally expressed and paternally methylated. It has been shown that methylation of the paternal allele coincides with a CpG-dense region and is critical for silencing the paternal allele. While the 5′ boundary of the differentially methylated region in p57 has been defined through previous research, the position of the 3′ boundary has not yet been investigated. The density of CpG dinucleotides diminishes in the 4th exon of the p57 gene; therefore, I want to test the hypothesis that the reduction in CpG density corresponds with the end of the differentially methylated region.
I am interested in determining if either or both the paternal and maternal alleles are methylated at the end of the p57 gene in exon 4 in somatic tissue. Because the CpG density becomes sparse in this area, I predict that biallelic methylation will predominate because that is what occurs 5′ of the CpG-rich region. If the parental alleles are biallelically methylated, this would suggest that the 3′ boundary is located in p57. If the alleles are differentially methylated, then this would suggest that the differentially methylated region extends beyond the CpG-rich region and that methylation outside of CpG-rich regions may also influence expression at the p57 gene.