Mentor: Dr. T. Davis
Despite recent discoveries, understanding heredity or the mechanism of transfer of traits from generation to generation remains a scientific challenge. Our genetic make-up is derived from a combination of maternal and paternal DNA. For most genes both sets of genetic material play a role in directing the development of the offspring. The exception to the rule is seen in genomic imprinting when the expression of genes is dependent on the parent of origin; in other words, only one of the two parental alleles inherited is expressed. This is a rare type of inheritance pattern which occurs in mammals. Of the 25,000 genes in humans there are only 80 known imprinted genes. The key to understanding the underlying complexity of this inheritance pattern is describing how the cell distinguishes which genetic material to express. The process of DNA methylation, to date, appears to be the best answer. DNA methylation is a type of epigenetic modification - a change in the DNA structure which affects the gene expression. DNA methylation adds a methyl (CH3) group to the cytosine in a cytosine and guanine (CG) dinucleotides pair of DNA. Hence, if one allele is methylated and the other isn't then the cellular machinery can easily distinguish between the two and regulate the expression. DNA methylation changes the structure of DNA and has been shown to play a role in gene regulation.
Many imprinted genes have been studied in the mouse genome; one such imprinted gene is the Gtl2 gene, which is located on chromosome 12. Gtl2 is maternally expressed and paternally methylated. There are two regions of paternal methylation that have been identified; the IG-DMR located upstream from the gene itself and the Gtl2-DMR at the beginning of the gene. These regions are believed to help in the regulation of the gene expression in the offspring. I am investigating the methylation status of a third region in Gtl2 termed e1. The e1 region of the Gtl2 gene is of particular interest because this area is known to have multiple promoters (transcription initiation sites), resulting in complex regulation of the gene. This region contains many alternate CG dinucleotides commonly associated with DNA methylation. My research this summer will be to analyze the intricate DNA methylation patterns at the alternative promoter regions located in the e1 region.
The mechanism of genomic imprinting regulates expression of genes required for embryonic growth and development. Research conducted on genomic imprinting and DNA methylation patterns promises to lead to a greater understanding of the role of this regulatory mechanism on development.