Mentor: Professor T. Davis
Unlike other genes, imprinted genes are expressed monoallelically, meaning that expression is restricted to only one of the two parental copies, either the paternal or the maternal one. This type of gene regulation is present only in mammals and is very uncommon: for example, out of the approximately 20,000 genes present in the human genome, only 80 imprinted genes have been discovered so far. Although they represent a very small fraction of all genes, they are very important in processes related to development and behavior, and defects in their expression can lead to anomalies such as abnormal growth and many others. Many imprinted genes are associated with regions of differential methylation, in which one parental allele of the gene is methylated while the other is not. This mark allows the cell to distinguish between the two different copies and to consequently regulate expression.
Gtl2 is an imprinted gene located on chromosome 12 in the mouse. This gene codes for an untranslated RNA that is thought to have a regulatory function. The maternal copy is unmethylated and expressed, while the paternal copy is methylated and silenced. The paternal methylation of the Gtl2 gene is present in two discrete regions: the Gtl2-DMR, at the beginning of the gene, and the IG-DMR, upstream from the gene. While the methylation on the Gtl2-DMR is absent in sperm and is established after fertilization, IG-DMR methylation is present in sperm. However, it is not clear whether this methylation is maintained throughout the early embryonic stages or is erased after fertilization and reestablished at a later developmental stage of embryogenesis.
In order to determine which of the two hypotheses is correct, I have been analyzing the mouse Gtl2 IG-DMR methylation pattern at different embryonic stages. The stages analyzed so far, 7.5 and 8.5-day embryos, show consistently methylated paternal alleles, while the maternal alleles are unmethylated. My research this summer will entail analyzing the methylation pattern of 3.5-day embryos. This particular stage will provide an important piece of information, as it is the least methylated stage of development of the mouse embryo, and therefore can be indicative of whether the paternal methylation is maintained throughout development.