Mentor: Dr. Tamara Davis
All mammals have two copies of DNA within each cell, one maternally inherited and the other paternally inherited. In the majority of genes, both copies are expressed. However, for a small number of alleles in which genomic imprinting occurs, only one copy is expressed. This is an unusual demonstration of gene regulation, which results from the altered structure of the chromosome itself. When genomic imprinting occurs, the paternal and maternal alleles can be silenced or expressed, depending upon the resulting structure.
The chromosome structure of an allele is the result of its interaction with histones. Histones are protein components of chromatin in eukaryotic cells. They act as spools around which the chromatin winds, compacting a very long strand of DNA (1.8 meters) into a condensed structure that will fit within the nucleus. Chemical modification of histones can change the degree of compaction of the DNA. Histones can be modified with methyl, phosphate, acetyl, and ubiquitin groups and these modifications can result in tighter or looser winding, which in turn affects how accessible the DNA is for transcription.
Our research is interested specifically in the gene Rasgrf1 in mouse, which is imprinted in some tissues, but not others. In imprinted tissue, such as brain, the paternally inherited allele is expressed, but the maternal allele is silent. However, in other tissues, such as lung, both the maternal and paternal alleles are expressed. We believe that these differences in expression are a result of chromosome structure differences in the maternal and paternal DNA. Therefore, we will investigate the differences in the histone modification of expressed paternal, expressed maternal, and silenced maternal alleles in different tissues.