Mentor: Dr. Tamara Davis
Most genes are expressed biallelicially; RNA transcripts are produced from the copy of the gene inherited from both parents. However, a subset of genes are genomically imprinted, resulting in monoallelic expression. Most imprinted genes are associated with a differentially methylated region (DMR) that has been implicated in the control of gene expression. Methylation can occur on cytosine residues in CpG dinucleotides, and is believed to influence expression. However, methylation cannot be the only influence on expression as imprinted expression has been observed in the absence of differential methylation.
Initial studies have identified the mouse gene Rasgrf1 as imprinted. Rasgrf1 is paternally methylated and paternally expressed. However, it has been shown that not all tissues show an imprinted expression pattern. Imprinting of Rasgrf1 has been observed in the brain, heart, and stomach of adult mice. In contrast, there is biallelic expression of Rasgrf1 in the lungs, thymus, testis, and ovary. Other tissues such as liver and kidney do not exhibit any expression in the adult. The presence of different expression patterns in different tissues allows us to investigate the relationship between methylation and expression.
My research will be to determine both the DNA methylation and the expression patterns at the Rasgrf1 locus in different tissues. I will conduct my experiments using F1 hybrid so that I can distinguish between the maternal and paternal alleles using DNA sequence polymorphisms. I will analyze tissues that exhibit monoallelic, biallellic and no expression in order to determine whether differential methylation correlates with differential methylation. If the methylation status of the DMR dictates the expression pattern it would be expected that there would be biallelic methylation in tissues that express the paternal and the maternal allele. My preliminary data suggests that the methylation data does not precisely correlate with expression. I have shown that the DNA in lung is differentially methylated despite biallelic expression. Therefore, there must be alternate mechanism for the control of Rasgrf1 expression.