Effect of H3K27me3 upregulation on Drosophila health



Florence R.C. Murray Professor of Biology; Investigator of the Howard Hughes Medical Institute

Project Summary

I worked at Bonini lab where I carried out a project investigating epigenetics in a  Drosophila model. Tri-methylation of lysine 27 on histone 3 (H3K27me3) is a well-known epigenetic mark for silenced regions of chromatin. Placement of the H3K27me3 mark is regulated by the activity of PRC2, the methyltransferase, and by Utx, the histone demethylase. To better understand the impact of global H3K27me3 on brain aging, we turned our attention in this project to animals with increased H3K27me3 levels. We hypothesized that animals with increased H3K27me3 would have increased mortality rates, decreased brain health, and be vulnerable to neurotoxicity. 
I learned techniques for assessing fly health from Ananth Srinivasan, a biology PhD candidate at Bonini lab. I used lifespan tracking and two forms of thin tissue sectioning to observe differences in aging and brain health across genotypes. Both of my experimental genotypes had upregulations for H3K27me3, either by upregulating PRC2 or downregulating Utx activity. The increased levels of H3K27me3 had been previously confirmed by western blots. I found that animals with upregulations in PRC2 had decreased mortality rates and greater presence of vacuoles in brain tissue. These findings indicate that H3K27me3 upregulated flies have shorter lifespans and greater neurodegeneration. In Utx-reduced flies, there was a greater accumulation of c11.2 protein which indicates greater susceptibility to neurotoxicity. Overall, these findings indicate that increased H3K27me3 expression has detrimental effects on Drosophila health, complementing previous findings on the protective feature of reduced H3K27me3.