Mentor: Professor Tamara Davis
Genomic imprinting is a mammalian-specific phenomenon that affects the expression of a subset of genes. Most genes are expressed from both the maternal and paternal alleles. Imprinted genes, however, have monoallelic expression dependant on parental origin. For some genes, the maternal allele is expressed while the paternal allele is silenced; the reverse is true for other imprinted genes. Approximately 80 imprinted genes have been identified in mice, most of which have homologous sequences and imprinting similarities in humans.
Imprinting refers to a molecular mark that distinguishes the parental origin of each allele of an imprinted gene. A common mechanism for marking one of the two alleles is through the addition of methyl groups (CH3) on cytosines that are adjacent to guanines in the nucleotide sequence. Although the mechanisms are not entirely understood, allele-specific DNA methylation and chromatin structure are thought to play a role in whether an allele is silenced or expressed. The differential expression observed in imprinted genes has implications for normal growth and development in humans as well as assisted reproductive technology, epigenetic regulation and evolutionary strategies.
The Rasgrf1 gene (RAS protein-specific guanine nucleotide-releasing factor 1) is an imprinted gene that plays a role in regulating postnatal growth by controlling the synthesis and release of a growth hormone. In one study, researchers found that mice with a mutant Rasgrf1 gene weighed 15% less than their wild-type littermates as adults. Scientists have suggested that the biochemical explanation for this is that Rasgrf1 is involved with controlling the release of insulin from β cells. Expression of Rasgrf1 has also been found in neurons in the brain and has implications for long-term memory and learning.
My research will focus on the Rasgrf1 gene in mice. Methyl groups that are added to certain portions of the DNA mark the paternal allele of Rasgrf1, which is expressed from only the paternally-inherited allele in many tissues. I will examine the methylation of this gene on the maternal and paternal alleles at different stages of embryonic and extra-embryonic development. The purpose of this study is to expand our understanding of the differential methylation in embryonic tissues and initiate novel research into the methylation patterns in extra-embryonic tissues. Placental development plays a critical role in the growth of the embryo and nothing is known about Rasgrf1 expression in this tissue. In addition, I will run an expression assay to understand where Rasgrf1 is being transcribed into mRNA in select embryonic and extra-embryonic tissues to examine imprinting status. This will help to determine the relationship between differential methylation and the actual expression of Rasgrf1.