Abstract: Sara Marlow
Mentor: Dr. Davis
All mammals have two sets of DNA within each cell, one maternally inherited and the other paternally inherited. For the majority of genes, both copies are expressed. However, about 100 mammalian genes have been identified as imprinted, in which only one parent’s copy of the gene is expressed. This is an unusual form of preferential gene regulation. Imprinted expression results as a consequence of differences in chromatin structure between the two parental alleles, which can influence the expression of the gene.
In order to accommodate DNA in the cell, it must be condensed. 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, and acetyl groups. These modifications can result in tighter or looser chromatin conformation, which in turn affects how accessible the DNA is for transcription. Therefore, differential distribution of modified histones on the parental allele of imprinted genes can result in the differential expression.
My research is focused on understanding how histone modifications affect the expression of the imprinted Rasgrf1 gene in mouse, which has a curious pattern of expression. In brain and liver, Rasgrf1 is only paternally expressed. In lung, kidney, stomach, and thymus, Rasgrf1 is both maternally and paternally expressed. Histone modifications can alter the structure of the chromatin, making the genes more or less difficult to transcribe, it is possible that differences in histone distribution may be responsible for the tissue-specific imprinting of Rasgrf1. I believe that these differences in expression are a result of chromosome structure differences in the maternal and paternal chromosomes, as a result of histone modification. Therefore, I expect to observe different modifications on the paternal versus maternal chromosomes. In addition, I expect to observe different modifications on the expressed versus silent alleles.
I will be investigating the histone modifications of expressed paternal and silenced maternal alleles in liver, a monoallelically expressing tissue and will compare my results with those collected by another member of my lab using chromatin derived from kidney, a monoallelically expressing tissue.