Lu Mei He and Liz Powell
Mentor: Dr. Tamara Davis
Genomic imprinting is a form of gene regulation in mammals that results in the preferential expression of one parental allele. DNA methylation, the addition of methyl groups at cytosine residues in CpG dinucleotides, has been proposed to identify which of the alleles should be expressed. Studies have also shown that methylation may control transcription by interfering with protein-DNA interactions. Differential methylation on the parental alleles can be acquired in one of two ways: inheritance at the time of fertilization from the gametes or acquisition at some point post-fertilization during embryonic development.
Our lab is interested in studying the mechanism and timing of methylation acquisition on the paternal allele of imprinted genes. The gene we are currently studying, Gtl2, is located on distal mouse chromosome 12 and codes for an untranslated mRNA. Data from our lab and others has shown that Gtl2 is expressed from the maternal allele and is associated with two paternally methylated regions. We are focusing on the differentially methylated region (DMR) located around the gene’s transcriptional start site. We want to determine when methylation is acquired at this region and also investigate the relationship between methylation and expression.
Previous studies have identified the Gtl2 promoter as a DMR containing paternal allele-specific methylation. I have demonstrated that methylation of the paternal allele is not inherited from the sperm; therefore, the acquisition on the paternal strand must be acquired sometime after fertilization. I will look at the methylation status of the maternal and paternal alleles at several stages of embryogenesis to determine the precise time at which methylation is acquired on the paternal allele. Then I will compare the time of methylation acquisition with that of Gtl2 expression. If methylation of the paternal allele plays a role in determining proper expression of Gtl2, we would predict that methylation must be acquired on the paternal allele prior to the onset of imprinted expression. My experiment, which will test this hypothesis, will allow for a greater understanding of the mechanism that underpins methylation acquisition for imprinted genes.