Analyzing differential methylation due to genomic imprinting of the Rasgrf1 gene in mice

Posted May 10th, 2010 at 2:14 pm.

Lauren Dockery

Mentor: Professor Tamara Davis

Genomic imprinting is a genetic and molecular phenomenon that is known to only occur in mammals, and only at a select few genes. In genomic imprinting, a particular gene’s expression is entirely dependent upon the parental origin, a concept known as monoallelic expression. The normal human genome consists of two copies of each of the approximately 20,000-25,000 genes: one inherited from the mother, and one from the father. Typically, both copies are controlled in the same manner within a particular cell. However, for the 80 known imprinted genes, some will only be maternally expressed while others will only be paternally expressed. The failure of a gene to properly imprint can lead to several known disorders in humans such as Prader-Willi and Angelman syndromes.

Differential methylation, the placement of a methyl (CH3 ) group at particular locations on a gene, serves as a way to distinguish parental origins of imprinted genes. For example, methylation of the paternal allele can be inherited from the sperm, while the oocyte contains an unmethylated copy. It is believed that differential methylation serves to regulate the silencing or expression of imprinted genes. Our lab investigates the relationship between methylation and expression at the paternally methylated and expressed Rasgrf1. Rasgrf1 (RAS protein-specific guanine nucleotide-releasing factor 1), an imprinted gene located on mouse chromosome 9, has been found to play a role in growth regulation as well as long-term memory formation.

While Rasgrf1 is considered an imprinted gene, its expression varies in different tissues. Rasgrf1 is imprinted in the brain; however, expression from both paternal and maternal alleles is observed in lung and thymus, while other tissues show no expression. Different patterns of expression profiles raise questions regarding the relationship between differential methylation and imprinted expression at Rasgrf1. For example, it has been clearly shown that methylation is necessary for expression in tissues where Rasgrf1 is imprinted. However, in tissues with biallelic expression, the maternal allele is not methylated. Therefore, expression cannot be entirely dependent upon methylation. My research will investigate the relationship between methylation and expression specific to Rasgrf1. I will confirm the expression pattern for Rasgrf1 in a variety of tissues, including liver, which has been reported to be non-expressing but in which we have detected expression. I will compare these results with data collected by others in order to gain a better understanding of the relationship between methylation and expression.

Filed under: 2007,Davis, Dr. Tamara,Dockery, Lauren by Ann Dixon

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