Bio 500 Research Spotlight: Benjamin French on the Elgin Lab

DNA in multicellular organisms is packaged into two major forms: euchromatin and heterochromatin. Euchromatin is more loosely packaged and contains most of our genes, while heterochromatin is more tightly packaged, contains only a small number of genes, and has high repeat density. It has been hypothesized that heterochromatin formation is a strategy to prevent spurious transcription of repetitious (junk) DNA (e.g., transposons).

I have been working in Dr. Elgin’s lab for the past two and a half years to analyze the characteristics of an unusual chromosome in Drosophila (fruit flies). The fourth chromosome of Drosophila melanogaster is unusual because this tiny chromosome is almost entirely heterochromatic yet contains about 80 protein-coding genes. In the Elgin lab, we use a combination of DNA manipulation experiments done in the wet lab and bioinformatic analyses done on the computer to identify factors that enable the expression of fourth chromosome genes within a mostly heterochromatic domain. One aspect of the bioinformatics analysis involves the use of phylogenetic footprinting to identify regulatory factors (e.g., transcription factor binding sites) that are conserved in multiple Drosophila species. To aid us with these bioinformatic analyses, students participating in the Genomics Education Partnership (GEP) — a consortium of faculty and students from over 100 colleges and universities — construct and submit gene models for multiple Drosophila species.

During my time in the Elgin lab, I have primarily been responsible for the computational analyses. I have participated in the analysis and correction of the gene models submitted by GEP students and used these gene models to identify the transcription start sites of fourth chromosome genes in several Drosophila species.

Using a set of motif analysis tools, I have been able to determine that the core promoters of D. melanogaster and D. biarmipes fourth chromosome genes are enriched in binding sites for topoisomerase II, which suggests that topoisomerase II might play a role in regulating the expression of fourth chromosome genes. Next, we plan to take this finding to the wet bench, where we will insert a gene with an altered topoisomerase II binding site into the fourth chromosome of flies to see if this affects the gene’s expression.